Abstract:AIM: To develop an artificial intelligence (AI) diagnosis model based on deep learning (DL) algorithm to diagnose different types of retinal vein occlusion (RVO) by recognizing color fundus photographs (CFPs). METHODS: Totally 914 CFPs of healthy people and patients with RVO were collected as experimental data sets, and used to train, verify and test the diagnostic model of RVO. All the images were divided into four categories [normal, central retinal vein occlusion (CRVO), branch retinal vein occlusion (BRVO), and macular retinal vein occlusion (MRVO)] by three fundus disease experts. Swin Transformer was used to build the RVO diagnosis model, and different types of RVO diagnosis experiments were conducted. The model’s performance was compared to that of the experts. RESULTS: The accuracy of the model in the diagnosis of normal, CRVO, BRVO, and MRVO reached 1.000, 0.978, 0.957, and 0.978; the specificity reached 1.000, 0.986, 0.982, and 0.976; the sensitivity reached 1.000, 0.955, 0.917, and 1.000; the F1-Sore reached 1.000, 0.955 0.943, and 0.887 respectively. In addition, the area under curve of normal, CRVO, BRVO, and MRVO diagnosed by the diagnostic model were 1.000, 0.900, 0.959 and 0.970, respectively. The diagnostic results were highly consistent with those of fundus disease experts, and the diagnostic performance was superior. CONCLUSION: The diagnostic model developed in this study can well diagnose different types of RVO, effectively relieve the work pressure of clinicians, and provide help for the follow-up clinical diagnosis and treatment of RVO patients.

Abstract:AIM: To investigate the impact of niosome nanoparticles carrying umbelliprenin (UMB), an anti-angiogenic and anti-inflammatory plant compound, on the expression of vascular endothelial growth factor (VEGF-A) and connective tissue growth factor (CTGF) genes in a human retinal pigment epithelium (RPE)-like retina-derived cell line. METHODS: UMB-containing niosomes were created, optimized, and characterized. RPE-like cells were treated with free UMB and UMB-containing niosomes. The IC50 values of the treatments were determined using an MTT assay. Gene expression of VEGF-A and CTGF was evaluated using real-time polymerase chain reaction after RNA extraction and cDNA synthesis. Niosomes’ characteristics, including drug entrapment efficiency, size, dispersion index, and zeta potential were assessed. Free UMB had an IC50 of 96.2 μg/mL, while UMB-containing niosomes had an IC50 of 25 μg/mL. RESULTS: Treatment with UMB-containing niosomes and free UMB resulted in a significant reduction in VEGF-A expression compared to control cells (P=0.001). Additionally, UMB-containing niosomes demonstrated a significant reduction in CTGF expression compared to control cells (P=0.05). However, there was no significant reduction in the expression of both genes in cells treated with free UMB. CONCLUSION: Both free UMB and niosome-encapsulated UMB inhibits VEGF-A and CTGF genes expression. However, the latter demonstrates significantly greater efficacy, potentially due to the lower UMB dosage and gradual delivery. These findings have implications for anti-angiogenesis therapeutic approaches targeting age-related macular degeneration.

Abstract:AIM: To investigate the impacts of angiotensin II (Ang II) on retinal artery changes in apolipoprotein E deficient (apoE -/-) mice. METHODS: ApoE -/- male mice were infused by minipumps with Ang II at 1000 ng/kg·min (Ang II group) or saline (control group) for 28d. They were underwent ophthalmic fundus examination on day 0, 14, and 28 of infusion. Histopathologic examination, ribonucleic acid (RNA) sequencing and local Ang II measurement of retinas were conducted. RESULTS: Ophthalmic fundus examination showed Ang II infusion promoted the formation of retinal arterial aneurysm-like lesions on day 28. Optical coherence tomography revealed the ganglion cell and inner plexiform layer (GCIPL) thickness in the control group was significantly thinner than that in Ang II group (P<0.001). Hematoxylin-eosin staining demonstrated diffused swelling of GCIPL layer and its disordered structure in Ang II group. Transmission electron microscopy showed Ang II infusion caused aggravation of atherosclerotic lesions, including increased swelling, roughness, disorganization of the retinal vasculature, and vacuoles formation. RNA-sequencing and gene ontology enrichment analysis demonstrated that the structure and function of cellular membrane might be disturbed and visual function might be compromised by Ang II. The local level of Ang II was higher in Ang II infusion group but did not show significant differences compared to the control group (P=0.086). CONCLUSION: Ang II infusion promotes the formation of retinal arterial aneurysm-like lesions in apoE -/- mice, causing aggravation of atherosclerotic lesions, more severe disorganization of the retinal vasculature and disturbance of the cellular membrane.

Abstract:AIM: To provide the direct evidence for the crucial role of trimethylamine N-oxide (TMAO) in vascular permeability and endothelial cell dysfunction under diabetic condition. METHODS: The role of TMAO on the in vitro biological effect of human retinal microvascular endothelial cells (HRMEC) under high glucose conditions was tested by a cell counting kit, wound healing, a transwell and a tube formation assay. The inflammation-related gene expression affected by TMAO was tested by real-time polymerase chain reaction (RT-PCR). The expression of the cell junction was measured by Western blotting (WB) and immunofluorescence staining. In addition, two groups of rat models, diabetic and non-diabetic, were fed with normal or 0.1% TMAO for 16wk, and their plasma levels of TMAO, vascular endothelial growth factor (VEGF), interleukin (IL)-6 and tumor necrosis factor (TNF)-α were tested. The vascular permeability of rat retinas was measured using FITC-Dextran, and the expression of zonula occludens (ZO)-1 and claudin-5 in rat retinas was detected by WB or immunofluorescence staining. RESULTS: TMAO administration significantly increased the cell proliferation, migration, and tube formation of primary HRMEC either in normal or high-glucose conditions. RT-PCR showed elevated inflammation-related gene expression of HRMEC under TMAO stimulation, while WB or immunofluorescence staining indicated decreased cell junction ZO-1 and occludin expression after high-glucose and TMAO treatment. Diabetic rats showed higher plasma levels of TMAO as well as retinal vascular leakage, which were even higher in TMAO-feeding diabetic rats. Furthermore, TMAO administration increased the rat plasma levels of VEGF, IL-6 and TNF-α while decreasing the retinal expression levels of ZO-1 and claudin-5. CONCLUSION: TMAO enhances the proliferation, migration, and tube formation of HRMEC, as well as destroys their vascular integrity and tight connection. It also regulates the expression of VEGF, IL-6, and TNF-α.

Abstract:AIM: To investigate the effects of Sonic hedgehog (Shh) gene-modified bone marrow mesenchymal stem cells (MSCs) on graft-induced retinal gliosis and retinal ganglion cells (RGCs) survival in diabetic mice. METHODS: Bone marrow-derived MSCs were genetically modified with the Shh gene to generate a stably transfected cell line of Shh-modified MSCs (MSC-Shh). Intravitreal injections of MSC-Shh and green fluorescent protein-modified MSCs (MSC-Gfp; control) were administered in diabetic mice. After 4wk, the effects of MSC-Shh on retinal gliosis were evaluated using fundus photography, and markers of gliosis were examined by immunofluorescence and Western blotting. The neurotrophic factors expression and RGCs survival in the host retina were evaluated using Western blotting and immunofluorescence. The mechanisms underlying the effects of MSC-Shh was investigated. RESULTS: A significant reduction of proliferative vitreoretinopathy (PVR) was observed after intravitreal injection of MSC-Shh compared to MSC-Gfp. Significant downregulation of glial fibrillary acidic protein (GFAP) was demonstrated in the host retina after MSC-Shh administration compared to MSC-Gfp. The extracellular signal-regulated kinase 1/2 (ERK1/2), protein kinase B (AKT) and phosphatidylin-ositol-3-kinase (PI3K) pathways were significantly downregulated after MSC-Shh administration compared to MSC-Gfp. Brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) levels were significantly increased in the host retina, and RGCs loss was significantly prevented after MSC-Shh administration. CONCLUSION: MSC-Shh administration reduces graft-induced reactive gliosis following intravitreal injection in diabetic mice. The ERK1/2, AKT and PI3K pathways are involved in this process. MSC-Shh also increases the levels of neurotrophic factors in the host retina and promoted RGCs survival in diabetic mice.

Abstract:AIM: To compare the three-dimensional choroidal vascularity index (CVI) and choroidal thickness between fellow eyes of acute primary angle-closure (F-APAC) and chronic primary angle-closure glaucoma (F-CPACG) and the eyes of normal controls. METHODS: This study included 37 patients with unilateral APAC, 37 with asymmetric CPACG without prior treatment, and 36 healthy participants. Using swept-source optical coherence tomography (SS-OCT), the macular and peripapillary choroidal thickness and three-dimensional CVI were measured and compared globally and sectorally. Pearson’s correlation analysis and multivariate regression models were used to evaluate choroidal thickness or CVI with related factors. RESULTS: The mean subfoveal CVIs were 0.35±0.10, 0.33±0.09, and 0.29±0.04, and the mean subfoveal choroidal thickness were 315.62±52.92, 306.22±59.29, and 262.69±45.55 μm in the F-APAC, F-CPACG, and normal groups, respectively. All macular sectors showed significantly higher CVIs and choroidal thickness in the F-APAC and F-CPACG eyes than in the normal eyes (P<0.05), while there were no significant differences between the F-APAC and F-CPACG eyes. In the peripapillary region, the mean overall CVIs were 0.21±0.08, 0.20±0.08, and 0.19±0.05, and the mean overall choroidal thickness were 180.45±54.18, 174.82±50.67, and 176.18±37.94 μm in the F-APAC, F-CPACG, and normal groups, respectively. There were no significant differences between any of the two groups in all peripapillary sectors. Younger age, shorter axial length, and the F-APAC or F-CPACG diagnosis were significantly associated with higher subfoveal CVI and thicker subfoveal choroidal thickness (P<0.05). CONCLUSION: The fellow eyes of unilateral APAC or asymmetric CPACG have higher macular CVI and choroidal thickness than those of the normal controls. Neither CVI nor choroidal thickness can distinguish between eyes predisposed to APAC or CPACG. A thicker choroid with a higher vascular volume may play a role in the pathogenesis of primary angle-closure glaucoma.

Abstract:AIM: To investigate the symmetry of upper eyelid in patients with unilateral mild and moderate blepharoptosis who underwent unilateral minimally invasive combined fascia sheath (CFS) suspension. METHODS: A retrospective study of patients who underwent unilateral minimally invasive CFS suspension surgery between January 2018 and December 2021. Inclusion criteria included unilateral mild and moderate ptosis, good levator muscle function (>9 mm) and follow-up of at least 6mo. Pre- and post-operative symmetry was graded subjectively for marginal reflex distance 1 (MRD1), tarsal platform show (TPS) and eyebrow fat span (BFS). A t-test was used to evaluate MRD1, TPS and BFS asymmetry by calculating delta values. The Bézier curve tool of the Image J software was used to extract the upper eyelid contours, where the symmetry was measured by the percentage of overlapping curvatures (POC). RESULTS: Totally 105 patients (105 eyelids) were included (mild group, n=84; moderate group, n=21). Postoperatively, all patients increased MRD1 and decreased TPS in the ptotic eye while maintaining unchanged BFS. The asymmetric delta value for MRD1 was measured to be 1.48±0.86 preoperatively, and it decreased to 0.58±0.67 postoperatively in all cases (P=0.0004). In patients with mild ptosis, the asymmetry value of TPS fell significantly from 1.15±0.62 to 0.68±0.38 (P=0.0187). The symmetry of the upper eyelid contour increased in all subgroups of patients, with a POC of 59.39%±13.45% preoperatively and POC of 78.29%±13.80% postoperatively. CONCLUSION: Minimally invasive CFS suspension is proved to be an effective means of improving the symmetry of unilateral ptosis in terms of MRD1 (all subgroups), POC (all subgroups) and TPS (only mild group), whereas BFS is unaffected.

Abstract:AIM: To develop normative data for meibomian gland dysfunction (MGD) parameters, using non-contact meibography technique of Sirius Costruzione Strumenti Oftalmici (CSO) machine, in an Egyptian population sample. METHODS: Observational, cross-sectional, analytic study, in which 104 Egyptian volunteers were included. Both upper lids were examined, using “Sirius CSO” machine. Each eyelid was given a degree of meibomian gland loss (MGL), which was calculated by the software of the machine. RESULTS: Mean percentage MGL in right upper lid was of 30.9%±12.6%, and that of left upper lid was 32.6%±11.8%. Thirty-four volunteers (32.7%) had first-degree MGL in their right upper lid, and 67.3% had second-degree loss. One volunteer (1%) had zero-degree MGL in left upper lid, 28 (26.9%) had first-degree loss, and 75 (72.1%) had second-degree loss. Degree of MGL in right upper eyelid was not related to age, but degree of MGL in left upper eyelid increased with age. There was statistically significant difference between both genders for degree of MGL in right eye (P=0.036) and in left eye (P=0.027). CONCLUSION: Noncontact meibography is a useful non-invasive tool for diagnosing MGL. MGL is diagnosed in 100% of apparently normal individuals; 26.9%-32.7% of which have first-degree MGL, and 67.3%-72.1% have second-degree MGL.

Abstract:AIM: To evaluate the effect of lens surgery on health-related quality of life (HRQoL) of preschool children with congenital ectopia lentis (CEL). METHODS: A prospective self-controlled study was conducted in Zhongshan Ophthalmic Center. Children aged from 5 to 7y whom were diagnosed with CEL and underwent phacoemulsification with scleral-fixated posterior chamber intraocular lens implantation and their parents were enrolled in this study. All of them completed the child and proxy (parental) PedsQL™ 4.0 before and after the surgery. Their preoperative scores were compared to their postoperative ones. Subgroup analyses were performed based on gender and preoperative bilateral presenting visual acuity of the children. RESULTS: Thirty-two children with CEL successfully underwent surgery without any complications, among whom 8 had monocular surgery and 24 had binocular surgery. Preoperative and postoperative questionnaires were completed by 32 child-parent pairs. Surgical intervention could significantly improve the vision of affected children (P<0.001). The medians of physical, psychosocial and total health scores self-reported by the children were 68.75 (62.50, 81.25), 65.00 (60.00, 80.00) and 67.39 (60.87, 78.26) preoperatively and were 93.75 (87.50, 100.00), 90.00 (83.33, 96.67) and 89.13 (85.32, 95.65) postoperatively. The preoperative scores of the affected children were significantly lower in all scales than age-matched healthy children (P<0.001). All the postoperative scores were significantly higher than the preoperative scores in affected children and their parents (P<0.001). In the physical functioning evaluation, the preoperative score reported by parents of girls was higher than parents of boys (P=0.041), and the postoperative score of girls was higher than that of boys (P=0.036). CONCLUSION: CEL is associated with significantly worse quality of life in preschool children. Surgical intervention can significantly improve the HRQoL in affected children from both personal and family perspective.

Abstract:AIM: To assess glaucoma patient satisfaction and follow-up adherence in case management and identify associated predictors to improve healthcare quality and patient outcomes. METHODS: In this cross-sectional study, a total of 119 patients completed a Patient Satisfaction Questionnaire-18 and a sociodemographic questionnaire. Clinical data was obtained from the case management system. Follow-up adherence was defined as completing each follow-up within ±30d of the scheduled time set by ophthalmologists during the study period. RESULTS: Average satisfaction scored 78.65±7, with an average of 4.39±0.58 across the seven dimensions. Age negatively correlated with satisfaction (P=0.008), whilst patients with follow-up duration of 2 or more years reported higher satisfaction (P=0.045). Multivariate logistics regression analysis revealed that longer follow-up durations were associated with lower follow-up adherence (OR=0.97, 95%CI, 0.95-1.00, P=0.044). Additionally, patients with suspected glaucoma (OR=2.72, 95%CI, 1.03-7.20, P=0.044) and those with an annual income over 100 000 Chinese yuan demonstrated higher adherence (OR=5.57, 95%CI, 1.00-30.89, P=0.049). CONCLUSION: The case management model proves effective for glaucoma patients, with positive adherence rates. The implementation of this model can be optimized in the future based on the identified factors and extended to glaucoma patients in more hospitals.

Abstract:AIM: To evaluate the efficacy and safety of perfluoro-n-octane (PFO) for ophthalmic surgery versus F-Octane as an intraoperative tamponade in pars plana vitrectomy (PPV) in management of retinal detachment. METHODS: This multicenter, prospective, randomized, double-masked, parallel-controlled, non-inferiority trial was conducted in three ophthalmology clinical centers in China. Patients with retinal detachment, who were eligible for PPV were consecutively enrolled. Participants were assigned to PFO for ophthalmic surgery or F-Octane for intraocular tamponade in a 1:1 ratio. Best-corrected visual acuity (BCVA), intraocular pressure (IOP) measurement, and dilated fundus examination were performed preoperatively and at 1, 7±1, 28±3d postoperatively. The primary outcome was complete retinal reattachment rate at postoperative day one. The non-inferiority margin was set at 9.8%. The secondary outcomes included intraoperative retinal reattachment rate, and mean changes in IOP and BCVA from baseline to 1, 7±1, 28±3d postoperatively, respectively. Safety analyses were presented for all randomly assigned participates in this study. RESULTS: Totally 124 eligible patients completed the study between Mar. 14, 2016 and Jun. 7, 2017. Sixty of them were randomly assigned to the PFO for ophthalmic surgery group, and 64 were assigned to the F-Octane group. Baseline characteristics were comparable between the two groups. Both groups achieved 100% retinal reattachment at postoperative day one (difference 0, 95%CI: -6.21% to 5.75%, P=1). The pre-defined noninferiority criterion was met. No significant difference was observed in intraoperative retinal reattachment rate (difference 1.77%, P=0.61), mean changes in IOP (difference 0.36, -0.09, 2.22 mm Hg at 1, 7±1, 28±3d postoperatively, with all P>0.05) and BCVA (difference 0.04, -0.02, 0.06 logMAR at 1, 7±1, 28±3d postoperatively, all P>0.05) between the two groups. No apparent adverse events related to the utilization of PFO were reported. CONCLUSION: In patients with retinal detachment undergoing PPV, PFO for ophthalmic surgery is non-inferior to F-Octane as an intraocular tamponade, and both are safe and well-tolerated.

Abstract:AIM: To evaluate the efficacy and safety of silicone oil (SO) as a corneal lubricant to improve visualization during vitrectomy. METHODS: Patients who underwent vitreoretinal surgery were divided into two groups. Group 1 was operated on with initial SO (Oxane 5700) as a corneal lubricant. Group 2 was operated on with initial lactated ringer’s solution (LRS) and then replaced with SO as required. Fundus clarity was scored during the surgery. Fluorescein staining was performed to determine the damage to corneal epithelium. RESULTS: Totally 114 eyes of 114 patients were included. Single SO use maintained a clear cornea and provided excellent visualization of surgical image. In group 1, the fundus clarity was grade 3 in 41/45 eyes and grade 2 in 4/45 eyes. In group 2, corneal edema frequently occurred after initial LRS use. The fundus clarity was grade 3 in 19/69 eyes, 2 in 37/69 eyes and 1 in 13/69 eyes (P<0.05). SO was applied in 29 eyes of initial LRS use with subsequent corneal edema, which eliminated the corneal edema in 26 eyes. Corneal fluorescein staining score in group 1 was 0 in 28 eyes, 1 in 11 eyes and 2 in 6 eyes, and 40, 20 and 9, respectively, in group 2 (all P>0.05). CONCLUSION: The use of SO as a corneal lubricant is effective and safe for preserving and improving corneal clarity and providing clear surgical field during vitrectomy.

Abstract:AIM: To assess diabetic macular edema (DME) progression during the early phases of the COVID-19 pandemic, when severe societal restrictions raised the concern of possible deterioration of health in patients with systemic conditions, particularly those requiring frequent office visits. METHODS: This is a multicenter retrospective chart review of 370 patients (724 eyes) with an established diagnosis of DME seen on 3 separate visits between January 2019 and July 2021. Period 1 was January 2019 to February 2020 (considered pre-COVID-19), period 2 was March 2020 to December 2020 (considered the height of the pandemic; highest level of pandemic-related clinical and societal regulations) and period 3 was January 2021 to July 2021 (re-adjustment to the new “pandemic norms”). Main outcome measures included visual acuity, body mass index (BMI), blood pressure (BP), hemoglobin A1c (HbA1c), macular thickness, patient adherence to scheduled ophthalmology visits, and DME treatment(s) received at each visit. To facilitate measurement of macular thickness, each macula was divided into 9 Early Treatment Diabetic Retinopathy Study (ETDRS)-defined macular sectors as measured by OCT imaging. RESULTS: There was no change of BMI, systolic BP, and diastolic BP between any of the time periods. HbA1c showed a very small increase from period 1 (7.6%) to period 2 (7.8%, P=0.015) and decreased back to 7.6% at period 3 (P=0.12). Macular thickness decreased for 100% of macular regions. The central macular thickness decreased across all 3 periods from 329.5 to 316.6 μm (P=0.0045). After analysis of multiple variables including HbA1c, BMI, adherence to scheduled appointments, different clinic centers, and treatment interventions, there was no easily identifiable subgroup of patients that experienced the increase in DME. CONCLUSION: DME doesn’t worsen during the COVID-19 pandemic, instead sustaining a very small but statistically significant improvement. While identifying a mechanism behind our findings is beyond the scope of this study, potential explanations may include a delay in retinal changes beyond our study period, an unexpected increase in treatment frequency despite pandemic restrictions, and an unanticipated pandemic-related improvement in some lifestyle factors that may have had a positive impact on DME.

Abstract:AIM: To identify a maculopathy patient caused by new recessive compound heterozygous variants in RP1L1. METHODS: Comprehensive retinal morphological and functional examinations were evaluated for the patient with RP1L1 maculopathy. Targeted sequence capture array technique was used to screen potential pathologic variants. Polymerase chain reaction and Sanger sequencing were used to confirm the screening results. RESULTS: Fundus examination showed round macular lesions appeared in both eyes. Optical coherence tomography showed that the inner segment/outer segment continuity was disorganized and disruptive in the left eye, but it was uneven and slightly elevated in the right eye. Fundus autofluorescence showed patchy hyper-autofluorescence in the macula. Visual field examination indicates central defects in both eyes. Electroretinogram (ERG) and multifocal ERG showed no obvious abnormalities. Fundus fluorescein angiography in the macula showed obviously irregular hyper-fluorescence in the right eye and slightly hyper-fluorescence in the left eye. We found that the proband carried a missense variant (c.1972C>T) and a deletion variant (c.4717_4718del) of RP1L1, which were originated from the parents and formed compound heterozygous variants. Both variants are likely pathogenic according to the ACMG criteria. Multimodal imaging, ERG and detailed medical history are important diagnostic tools for differentiating between acquired and inherited retinal disorders. CONCLUSION: A maculopathy case with detailed retinal phenotype and new recessive compound heterozygous variants of RP1L1 is identified in a Chinese family, which expands the understanding of phenotype and genotype in RP1L1 maculopathy.

Abstract:AIM: To compare superficial and deep vascular properties of optic discs between crowded discs and controls using optical coherence tomography angiography (OCT-A). METHODS: Thirty patients with crowded discs, and 47 control subjects were enrolled in the study. One eye of each individual was included and OCT-A scans of optic discs were obtained in a 4.5×4.5 mm2 rectangular area. Radial peripapillary capillary (RPC) density, peripapillary retinal nerve fiber layer (pRNFL) thickness, cup volume, rim area, disc area, cup-to-disc (c/d) area ratio, and vertical c/d ratio were obtained automatically using device software. Automated parapapillary choroidal microvasculature (PPCMv) density was calculated using MATLAB software. When the vertical c/d ratio of the optic disc was absent or small cup, it was considered as a crowded disc. RESULTS: The mean signal strength index of OCT-A images was similar between the crowded discs and control eyes (P=0.740). There was no difference in pRNFL between the two groups (P=0.102). There were no differences in RPC density in whole image (P=0.826) and peripapillary region (P=0.923), but inside disc RPC density was higher in crowded optic discs (P=0.003). The PPCMv density in the inner-hemisuperior region was also lower in crowded discs (P=0.026). The pRNFL thickness was positively correlated with peripapillary RPC density (r=0.498, P<0.001). The inside disc RPC density was negatively correlated with c/d area ratio (r=-0.341, P=0.002). CONCLUSION: The higher inside disc RPC density and lower inner-hemisuperior PPCMv density are found in eyes with crowded optic discs.

Abstract:AIM: To investigate the difference of medial rectus (MR) and lateral rectus (LR) between acute acquired concomitant esotropia (AACE) and the healthy controls (HCs) detected by magnetic resonance imaging (MRI). METHODS: A case-control study. Eighteen subjects with AACE and eighteen HCs were enrolled. MRI scanning data were conducted in target-controlled central gaze with a 3-Tesla magnetic resonance scanner. Extraocular muscles (EOMs) were scanned in contiguous image planes 2-mm thick spanning the EOM origins to the globe equator. To form posterior partial volumes (PPVs), the LR and MR cross-sections in the image planes 8, 10, 12, and 14 mm posterior to the globe were summed and multiplied by the 2-mm slice thickness. The data were classified according to the right eye, left eye, dominant eye, and non-dominant eye, and the differences in mean cross-sectional area, maximum cross-sectional area, and PPVs of the MR and LR muscle in the AACE group and HCs group were compared under the above classifications respectively. RESULTS: There were no significant differences between the two groups of demographic characteristics. The mean cross-sectional area of the LR muscle was significantly greater in the AACE group than that in the HCs group in the non-dominant eyes (P=0.028). The maximum cross-sectional area of the LR muscle both in the dominant and non-dominant eye of the AACE group was significantly greater than the HCs group (P=0.009, P=0.016). For the dominant eye, the PPVs of the LR muscle were significantly greater in the AACE than that in the HCs group (P=0.013), but not in the MR muscle (P=0.698). CONCLUSION: The size and volume of muscles dominant eyes of AACE subjects change significantly to overcome binocular diplopia. The LR muscle become larger to compensate for the enhanced convergence in the AACE.

Abstract:AIM: To evaluate the reliability of Photo-Hirschberg screening for global strabismus performed by non-specialized personnel. METHODS: Participants at three sites were enrolled. One person at each site was trained in visual acuity measurement and use of the computerized system. Visual acuity was measured, and strabismus testing was performed using two flash photographs. All data from the three primary observers were sent to an experienced assistant researcher, who was blinded to the primary results, for re-evaluation. The primary and re-evaluation results of the Photo-Hirschberg screenings using weighted kappa for agreement were compared. RESULTS: The study included 181 participants (88 males and 93 females) and the results for primary and re-evaluation screenings were corresponded. Ten participants with contrasting results presented with unclear corneal light reflex. Sensitivity and specificity were 100% [95% confidence interval (CI): 29.0%–100%] and 99.4% (95%CI: 96.6%–100%), respectively, based on the Agresti test of the primary evaluation, considering the re-evaluated classification as true. CONCLUSION: The computerized system can be used for primary strabismus screening by non-specialized personnel, with 98.8% agreement with specialists. However, it cannot be used as a substitute for professional examination.

Abstract:AIM: To evaluate the alterations of the retinal microvasculature and foveal avascular zone in patients with Parkinson’s disease (PD) using optical coherence tomography angiography (OCT-A). METHODS: A retrospective study of PD patients examined in the Ophthalmology Department of the General Hospital of Athens, “Georgios Gennimatas” from March 2021 to March 2022 was conducted. Totally 44 patients with PD were included and 18 healthy controls were examined, hence a total of 124 eyes were enrolled in the study. The foveal and parafoveal superficial and deep capillary plexus vascular density (fSCP-VD, fDCP-VD, pSCP-VD, pDCP-CD) and foveal avascular zone (FAZ) were quantified with OCTA. Optical coherence tomography (OCT) was used to measure macular thickness. Our statistical analysis was conducted by using a mixed effect linear regression model. RESULTS: After adjustment for age and gender, the mean parafoveal superficial capillary plexus vascular density (pSCP-VD) and mean parafoveal deep capillary plexus vascular density (pDCP-VD) were significantly decreased in individuals with PD (P<0.001 in both) by -2.35 (95%CI -3.3, -1.45) and -7.5 (95%CI -10.4, -4.6) respectively. fSCP-VD and fDCP-VD didn’t approach statistical significance. The FAZ area and perimeter were significantly decreased (P<0.001 in both) by -0.1 mm2 (95%CI -0.13, -0.07) and -0.49 mm2 (95%CI -0.66, -0.32) respectively. Circularity didn’t approach statistical significance. Central retinal thickness (CRT) was significantly decreased in individuals with PD (P<0.001) by -23.1 μm (95%CI -30.2, -16) and temporal retinal thickness (TRT) was decreased (P=0.025) by -11 μm (95%CI -22, -1.5) while nasal retinal thickness (NRT) only approached statistical significance (P=0.066). CONCLUSION: The mean pSCP-VD, pDCP-VD, CRT and TRT are significantly decreased and FAZ is altered in individuals with PD. These findings can be potentially used as biomarkers for the diagnosis and evaluation of early PD.

Abstract:AIM: To investigate sex-based differences in the occurrence of intra-operative and post-operative complications and associated visual outcomes following cataract surgery. METHODS: This was a retrospective study of patients who had phacoemulsification cataract surgery at the University of Colorado School of Medicine. Data collected included the patient’s health history, ocular comorbidities, operative and post-operative complications, and the post-operative best corrected visual acuity (BCVA). The data were analyzed using univariate and multivariable logistic regression with generalized estimating equations to account for the correlation of some patients having two eyes included in the study. RESULTS: A total of 11 977 eyes from 7253 patients were included in the study. Ocular comorbidities differed by sex, with males having significantly higher percentages of traumatic cataracts (males 0.7% vs females 0.1%), prior ocular surgery (6.7% vs 5.5%), and mature cataracts (2.8% vs 1.9%). Conversely, females had significantly higher rates of pseudoexfoliation (2.0% vs 3.2%). In unadjusted analysis, males had higher rates of posterior capsular rupture (0.8% vs 0.4%) and vitreous loss (1.0% vs 0.6%), but this difference was not significant after adjustment for confounders. Males had a significantly increased risk of post-operative retinal detachment, but in multivariable analysis this was no longer significant. Males were significantly less likely to undergo post-operative neodymium-doped yttrium aluminum garnet (Nd:YAG) laser capsulotomy for posterior capsule opacification (OR=0.8, 95%CI=0.7-0.9, P=0.0005). The BCVA was slightly worse for males pre-operatively; but post-operatively, both sexes exhibited similar visual acuity of Snellen equivalent 20/25. CONCLUSION: The study finds that in a cohort of patients presenting for cataract surgery, sex differences exist in pre-operative comorbidities and surgical characteristics that contribute to higher rates of some complications for males. However, observed surgical complication rates exhibit almost no difference by sex after adjusting for pre-operative differences and post-operative BCVA is similar between sexes.

Abstract:AIM: To provide a comprehensive and more representative national data on the disease, especially on treatment options and outcomes, and to determine access of retinoblastoma patients from Luzon, Visayas and Mindanao to eye care, and determine if access is associated with delay in consultation, staging and outcomes. METHODS: Cohort study of retinoblastoma patients seen in eleven institutions located in the three major areas of the Philippines namely Luzon, Vizayas and Mindanao from 2010-2020. RESULTS: Totally 636 patients, involving 821 eyes, were included. Majority (57%) were from Luzon and were seen in institutions in Luzon (72%). Annually, 58±10 new cases were seen with 71% having unilateral disease. Median delay of consultation remained long at 9 (3, 17)mo, longest in patients with unilateral disease (P<0.02) and those from the Visayas (P<0.003). Based on the International Retinoblastoma Staging System, only 35% of patients had Stage 1 while 47% already had extraocular disease. Enucleation was the most common treatment received by 484 patients while intravenous chemotherapy was received by 469. There were 250 (39%) patients alive, 195 (31%) dead, 85 (13%) abandoned, 17 (3%) refused and 89 (14%) with no data. CONCLUSION: This study presents the largest cohort of retinoblastoma patients in the Philippines in terms of patients’ and participating institutions’ number and geographical location and type of institution (private and public). It also presents more comprehensive data on the treatments used and outcomes (survival, globe salvage, and vision retention rates). Delay in consultation was still long among patients leading to advanced disease stage and lower survival rate. Despite increasing capacity to diagnose and manage retinoblastoma in the country, the delay of consultation remains long primarily due to accessibility issues to eye care institutions especially in the Visayas and financial concerns. The delay was still significant that overall survival rate remain low.

Abstract:AIM: To explore the factors influencing individuals’ willingness to participate in ophthalmic clinical trials. METHODS: A questionnaire survey was conducted from January to April 2021 among patients and their family members at Zhongshan Ophthalmic Center, Sun Yat-sen University, in Guangzhou, China. The survey gathered data on respondents’ willingness, demographic and socioeconomic profiles, as well as their reasons and concerns regarding engagement in clinical trials. RESULTS: Of the 1078 residents surveyed (mean age 31.2±13.1y; 65.8% females) in Guangzhou, 749 (69.5%) expressed a willingness to participate in future ophthalmic clinical trials. Specific characteristics associated with greater willingness included a younger age, lower annual income, higher education, prior participation experience, previous ophthalmic treatment, and a better understanding of clinical trials. With the exception of age, these characteristics were significantly linked to a higher willingness. The primary barrier to participation, expressed by 64.8% of those willing and 54.4% of those unwilling, was “Uncertain efficacy”. In terms of motivations, the willing group ranked “Better therapeutic benefits” (35.0%), “Professional monitoring” (34.3%), and “Trust in healthcare professionals” (33.1%) as their top three reasons, whereas the unwilling participants indicated “Full comprehension of the protocol” (46.2%) as the key facilitator. CONCLUSION: This study reveals a substantial willingness to participate in ophthalmic clinical trials and demonstrates the predictive role of demographic and socioeconomic factors. Variations in motivators and concerns between willing and unwilling participants highlight the significance of tailored recruitment strategies. Importantly, the need for and trust in healthcare professionals stand out as powerful motivations, underscoring the importance of enhancing physician-patient relationships, adopting patient-centered communication approaches, and addressing individualized needs to improve accrual rates.

Abstract:AIM: To evaluate lacrimal gland adenoid cystic carcinoma (LGACC) of prognosis in patients who underwent different treatment regimens. METHODS: We searched PubMed, EMBASE, and the Cochrane Library for studies done on the treatment of LGACC, between January 1987 and April 2022. A Meta-analysis was conducted to pool the 5-year overall survival rate (OR), and the 5-year recurrence rate (RR) and 5-year metastasis rate (MR) were assessed. RESULTS: The 30 studies involved 585 patients were included in the Meta-analysis. The pooled 5-year OR with surgery alone was 50%, the 5-year RR was 63%, and the 5-year MR was 34%. The pooled 5-year OR with surgery and adjuvant radiotherapy combined was 67% (95%CI 61%,73%), the 5-year RR was 41%, and the 5-year MR was 35%. The pooled 5-year OR with surgery and adjuvant chemoradiotherapy combined was 72% (95%CI 59%, 84%), the 5-year RR was 48%, and the 5-year MR was 36%. The pooled 5-year OR with surgery, intra-arterial cytoreductive chemotherapy, and adjuvant chemoradiotherapy combined was 78% (95%CI 68%, 89%), the 5-year RR was 15%, and the 5-year MR was 27%. CONCLUSION: Comprehensive treatment is more effective than surgery alone. Surgery combined with intra-arterial chemotherapy and adjuvant chemoradiotherapy seems to add value to the therapeutic effect of comprehensive treatment of LGACC but further high-quality research is required to validate this.

Abstract:AIM: To review recent innovations, challenges, and applications of small incision lenticule extraction (SMILE) extracted lenticule for treating ocular disorders. METHODS: A literature review was performed in the PubMed database, which was last updated on 30 December 2021. There was no limit regarding language. The authors evaluated the reference lists of the collected papers to find any relevant research. RESULTS: Due to the simplicity and accuracy of modern femtosecond lasers and the extensive development of SMILE surgery, many healthy human corneal stromal lenticules were extracted during surgery, motivating some professionals to investigate the SMILE lenticule reusability in different ocular disorders. In addition, new approaches had been developed to preserve, modify, and bioengineer the corneal stroma, leading to the optimal use of discarded byproducts such as lenticules from SMILE surgery. The lenticules can be effectively re-implanted into the autologous or allogenic corneas of human subjects to treat refractive errors, corneal ectasia, and corneal perforation and serve as a patch graft for glaucoma drainage devices with better cosmetic outcomes. CONCLUSION: SMILE-extracted lenticules could be a viable alternative to human donor corneal tissue.

Abstract:AIM: To summarize the application of deep learning in detecting ophthalmic disease with ultrawide-field fundus images and analyze the advantages, limitations, and possible solutions common to all tasks. METHODS: We searched three academic databases, including PubMed, Web of Science, and Ovid, with the date of August 2022. We matched and screened according to the target keywords and publication year and retrieved a total of 4358 research papers according to the keywords, of which 23 studies were retrieved on applying deep learning in diagnosing ophthalmic disease with ultrawide-field images. RESULTS: Deep learning in ultrawide-field images can detect various ophthalmic diseases and achieve great performance, including diabetic retinopathy, glaucoma, age-related macular degeneration, retinal vein occlusions, retinal detachment, and other peripheral retinal diseases. Compared to fundus images, the ultrawide-field fundus scanning laser ophthalmoscopy enables the capture of the ocular fundus up to 200° in a single exposure, which can observe more areas of the retina. CONCLUSION: The combination of ultrawide-field fundus images and artificial intelligence will achieve great performance in diagnosing multiple ophthalmic diseases in the future.

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