TENAYA and LUCERNE: Two-Year Results from the Phase 3 Neovascular Age-Related Macular Degeneration Trials of Faricimab with Treat-and-Extend Dosing in Year 2.

PURPOSE: To evaluate 2-year efficacy, durability, and safety of the bispecific antibody faricimab, which inhibits both angiopoietin-2 and VEGF-A. DESIGN: TENAYA (ClinicalTrials.gov identifier, NCT03823287) and LUCERNE (ClinicalTrials.gov identifier, NCT03823300) were identically designed, randomized, double-masked, active comparator-controlled phase 3 noninferiority trials. PARTICIPANTS: Treatment-naive patients with neovascular age-related macular degeneration (nAMD) 50 years of age or older. METHODS: Patients were randomized (1:1) to intravitreal faricimab 6.0 mg up to every 16 weeks (Q16W) or aflibercept 2.0 mg every 8 weeks (Q8W). Faricimab fixed dosing based on protocol-defined disease activity at weeks 20 and 24 up to week 60, followed up to week 108 by a treat-and-extend personalized treatment interval regimen. MAIN OUTCOME MEASURES: Efficacy analyses included change in best-corrected visual acuity (BCVA) from baseline at 2 years (averaged over weeks 104, 108, and 112) and proportion of patients receiving Q16W, every 12 weeks (Q12W), and Q8W dosing at week 112 in the intention-to-treat population. Safety analyses included ocular adverse events (AEs) in the study eye through study end at week 112. RESULTS: Of 1326 patients treated across TENAYA/LUCERNE, 1113 (83.9%) completed treatment (n = 555 faricimab; n = 558 aflibercept). The BCVA change from baseline at 2 years was comparable between faricimab and aflibercept groups in TENAYA (adjusted mean change, +3.7 letters [95% confidence interval (CI), +2.1 to +5.4] and +3.3 letters [95% CI, +1.7 to +4.9], respectively; mean difference, +0.4 letters [95% CI, -1.9 to +2.8]) and LUCERNE (adjusted mean change, +5.0 letters [95% CI, +3.4 to +6.6] and +5.2 letters [95% CI, +3.6 to +6.8], respectively; mean difference, -0.2 letters [95% CI, -2.4 to +2.1]). At week 112 in TENAYA and LUCERNE, 59.0% and 66.9%, respectively, achieved Q16W faricimab dosing, increasing from year 1, and 74.1% and 81.2%, achieved Q12W or longer dosing. Ocular AEs in the study eye were comparable between faricimab and aflibercept groups in TENAYA (55.0% and 56.5% of patients, respectively) and LUCERNE (52.9% and 47.5% of patients, respectively) through week 112. CONCLUSIONS: Treat-and-extend faricimab treatment based on nAMD disease activity maintained vision gains through year 2, with most patients achieving extended dosing intervals. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Development of high-performance point-of-care aqueous VEGF detection system and proof-of-concept validation in RVO patients.

OBJECTIVES: To develop a sensitive point-of-care testing (POCT) aqueous vascular endothelial growth factor (VEGF) detection system, and assess its role for predicting the response to anti-VEGF treatment in macular edema secondary to retinal vein occlusion (RVO-ME) patients. METHODS: An automatic point-of-care aqueous humor Magnetic Particle Chemiluminescence Enzyme Immuno-Assay (MPCLEIA) VEGF detection system was developed. The predictive values of aqueous cytokine levels, in combination with imaging parameters, on anatomical treatment response (ATR, the relative central macular thickness change [ΔCMT/bl-CMT]) were analyzed. RESULTS: The automatic MPCLEIA system was able to provide results in 45 min with only 20 µL sample. Among the 57 eyes with available pre- and post-treatment evaluation, ATR significantly correlated with levels of interleukin (IL)-6, IL-8, monocyte chemoattractant protein-1 (MCP-1) and VEGF measured by Luminex xMAP platform, and VEGF measured by MPCLEIA. Optimal cut-off values for these biomarkers were 13.26 ng/L, 23.57 ng/L, 1,110.12 ng/L, 105.52 ng/L, and 85.39 ng/L, respectively. Univariate analysis showed significant associations between ATR category (good response if ATR≤-25 % or poor response otherwise) and IL-6, IL-8, MCP-1, VEGF-xMAP, and VEGF-MPCLEIA (p<0.05). Multivariate logistic regression revealed that ATR category was significantly associated with aqueous VEGF-MPCLEIA (p=0.006) and baseline(bl)-CMT (p=0.008). Receiver operating characteristics analysis yielded an AUC of 0.959 for the regression model combining VEGF-MPCLEIA and bl-CMT, for predicting ATR category. CONCLUSIONS: Our novel MPCLEIA-based automatic VEGF detection system enables accurate POCT of aqueous VEGF, which shows promise in predicting the treatment response of RVO-ME to anti-VEGF agents when combined with bl-CMT.

Differences between young and elderly polypoidal choroidal vasculopathy patients with and without pachychoroid phenotypes.

PURPOSE: To investigate the distinct characteristics between young and elderly polypoidal choroidal vasculopathy (PCV) patients based on the pachy- or non-pachychoroid phenotypes. METHODS: PCV patients treated with intravitreal injections of Conbercept based on the 3 + PRN regimen from 27 centers of China PCV Research Alliance were included. Patients were categorized into the young and the elderly aged group based on the cut-off point determined using the Youden method according to the pachychoroid phenotypes. The characteristics of past medical history, lifestyle factors, fundus manifestations, and treatment response between the subgroups were analyzed. RESULTS: Three hundred eight eligible patients were included. Multivariate logistic regression showed a significant association between age and PCV subtype classification (OR = 0.921, P = 0.002). A cutoff age of 64.5 effectively distinguished between pachychoroid PCV and non-pachychoroid PCV (P < 0.001). Elderly PCV patients had a higher incidence of hypertension history (P = 0.044) but a lower incidence of diabetes history (P = 0.027). In terms of lifestyle, smoking history (P = 0.015) and staying up late (P = 0.004) were more significant in the young group of PCV patients. For clinical characteristics, the proportion of hemorrhagic PCV in the young group was significantly higher (P = 0.038), with a higher proportion of sharp-peaked PED (P = 0.049), thicker choroid (P < 0.001) but a lower portion of double-layer sign (P = 0.023) in OCT. Both groups showed significant anatomical changes compared to baseline in each follow-up period (P < 0.05), with the young group having a higher proportion of good anatomical response after the first injection (P = 0.009). CONCLUSION: PCV patients stratified by subtype exhibit distinct characteristics between the young and elderly groups.

Evaluation of the First-Dose Anti-VEGF Anatomical Response in Polypoidal Choroidal Vasculopathy Patients: Correlation with the Third-Dose Response and Risk Factor Analysis.

INTRODUCTION: The aims of the study were to investigate whether first-dose efficacy can predict third-dose anatomical response and analyze the risk factors for first-dose response of polypoidal choroidal vasculopathy (PCV) patients. METHODS: We retrospectively reviewed patients' medical records from 27 centers of China PCV Research Alliance. PCV patients treated with intravitreal injections of conbercept (IVC) based on the 3+ pro re nata regimen (three initial monthly injections, followed by injections as needed) with complete 3-month injection data were included. Response correlations, risk factor associations, changes in central macular thickness (CMT) or best-corrected visual acuity (BCVA), and number of injections in the first year of follow-up were evaluated separately in the pachy-PCV and non-pachy-PCV phenotypes. RESULTS: Overall, 165 eligible patients were included. There was a significant correlation between first-dose and third-dose anatomical response in pachy-PCV or non-pachy-PCV patients (rs = 0.611, p < 0.001; rs = 0.638, p < 0.001). Multivariate analysis revealed associations of good first-dose anatomical response in pachy-PCV patients with baseline CMT with a predicted area under the curve (AUC) of 0.847, while a good response in non-pachy-PCV patients was associated with baseline BCVA, baseline CMT, pigment epithelial detachment (PED) height, higher proportion of intraretinal fluid, and lower PED minimum diameter with a predicted AUC of 0.940. CMT in the good first-dose response group was significantly decreased from baseline at all first-year follow-up visits in both groups (p < 0.001), and mean BCVA was improved in the good versus poor first-dose anatomical response group (5.4 vs. 1.6 ETDRS letters in pachy-PCV, 10.6 vs. 7.4 letters in non-pachy-PCV) after the third injection. No significant difference was observed in the number of injections in the first year of follow-up between different response groups. CONCLUSION: In PCV patients receiving IVC, the first- and third-dose responses are significantly correlated, and different factors influence the first-dose response in different subtypes of PCV.

Comparison of three-dimensional heads-up system versus traditional microscopic system in medical education for vitreoretinal surgeries: a prospective study.

BACKGROUND: To compare the value and efficiency of the three-dimensional (3D) heads-up surgical system and traditional microscopic (TM) system in teaching and learning vitreoretinal surgeries. METHODS: Twenty ophthalmologists and scrub nurses were recruited as teachers, and 45 junior ophthalmology residents and trainee doctors, trainee nurses, and medical students were recruited as observers. Each teacher and observer were assigned to both a 3D-assisted and TM-assisted vitreoretinal surgery and then asked to complete satisfaction questionnaires for both surgical systems at the end of each surgery. RESULTS: The 3D heads-up surgical system was rated significantly higher in most of the subscales and overall satisfaction score by both teachers and observers (P < 0.05). However, ratings for instrument adjustment were significantly higher in the TM group compared to the 3D group for junior ophthalmology residents and trainee doctors (6.1 ± 1.7 vs. 8.8 ± 1.1, P < 0.001). CONCLUSIONS: The 3D heads-up surgical system has great didactical value in the medical education of vitreoretinal surgeries, but it is important to consider the specific needs of different learners when choosing between the two systems. TRIAL REGISTRATION: Not applicable.

Polarization- and angle-insensitive broadband long wavelength infrared absorber based on coplanar four-sized resonators.

In many potential applications, there is a high demand for long wavelength infrared (LWIR) absorbers characterized by a compact configuration, broad operational bandwidth, high absorption efficiency, and polarization- and angle-insensitive characteristics. In this study, we design and demonstrate a high-performance broadband LWIR absorber based on coplanar four-sized resonators, consisting of arrays of titanium (Ti) disks with different diameters supported by a continuous zinc selenide (ZnSe) layer and by a Ti film acting as a back-reflector. Particle swarm optimization (PSO) is employed to optimize the complicated geometry parameters, and the final optimized device exhibits near-unity absorption (∼96.7%) across the entire operational bandwidth (8 µm∼14 µm) under unpolarized normal incidence, benefiting from the impedance-matching condition and the multiple surface plasmon resonances of this configuration. Furthermore, the proposed absorber is insensitive to the angle of incidence due to the localized surface plasmon resonances supported by these four-sized resonators, and is insensitive to the state of polarization thanks to the highly symmetric feature of the circular pattern. The measured absorption of the fabricated sample exhibits a relatively high coincidence with the simulation, with an average absorption of 88.9% ranging from 8 µm to 14 µm. The proposed absorber, which can be easily integrated into a standardized micro/nano manufacture process for cost-effective large-scale production, provides a feasible solution for improving optical performance in thermal emitter, infrared detection, and imaging applications. Furthermore, the generalized design principle employing the optimized method opens up new avenues for realizing target absorption, reflection, and transmission based on more complicated structure configurations.

Surgery-related characteristics, efficacy, safety and surgical team satisfaction of three-dimensional heads-up system versus traditional microscopic equipment for various vitreoretinal diseases.

PURPOSE: To compare the three-dimensional (3D) heads-up surgery with the traditional microscopic (TM) surgery for various vitreoretinal diseases. METHODS: A medical record review of patients that underwent 3D heads-up or TM vitreoretinal surgeries was performed from May 2020 to October 2021 in this retrospective case-control study. Main outcome measures included surgery-related characteristics, efficacy, safety, and satisfaction feedback from the surgical team. RESULTS: A total of 220 (47.6%) and 242 (52.4%) eyes were included in the 3D and TM groups, respectively. The 3D heads-up system significantly benefits delicate surgical steps, like the epiretinal membrane (ERM) peeling for ERM and internal limiting membrane peeling for idiopathic macular holes (P < 0.05). The 3D heads-up system could facilitate a significantly better visual outcome for pathologic myopic foveoschisis (P = 0.049), while no difference by TM surgery (P = 0.45). For the satisfaction feedback, the 3D heads-up system was rated significantly higher in most subscales and the overall score (P < 0.05). The surgeons' ratings on operating accuracy and the first assistants' rating on operating accuracy and operation cooperation were significantly higher in the TM group than in the 3D group (P < 0.05). Besides that, the 3D heads-up surgery was comparable with TM surgery in the surgery-related characteristics, choice of tamponades, postoperative VA, primary anatomic success, and perioperative complications (P > 0.05). CONCLUSION: The efficacy and safety of the 3D heads-up surgery were generally comparable to the TM surgery. The 3D heads-up system could significantly benefit delicate surgical steps and achieve better surgical team satisfaction.

THERAPEUTIC EFFECT OF USING AUTOLOGOUS PLATELET CONCENTRATE IN VITRECTOMY FOR MACULAR HOLE: A Systematic Review and Meta-Analysis.

PURPOSE: To summarize the current evidence regarding the therapeutic effect of using autologous platelet concentrate (APC) in vitrectomy for macular hole (MH). METHODS: The PubMed, Web of Science, and Embase databases were searched according to the PROSPERO protocol (CRD42022366202). Controlled trials comparing whether APC was used in the vitrectomy of MH were included. The primary outcome was the closure rate of MH and postoperative best-corrected visual acuity, and the secondary outcome was the incidence of different types of complications. RESULTS: Seven studies that included 634 eyes were eligible. For the primary outcome, the usage of APC significantly improved the closure rate of MH in vitrectomy (odds ratio [OR] = 5.34, 95% confidence interval, 2.83-10.07, P < 0.001). Postoperative visual acuity did not significantly differ between the APC group and similar baseline controls (SMD = -0.07, 95% confidence interval, -0.35 to 0.22, P = 0.644). For the secondary outcome, using APC did not result in additional complications regarding postoperative retinal detachment or the recurrence of MH. CONCLUSION: The use of APC in vitrectomy was associated with a superior closure rate of the hole and no additional complications; therefore, it is effective and safe in MH surgery.

A novel surgical approach for fixation of a posterior chamber intraocular lens of Rayner 620 H with Gore-Tex suture.

PURPOSE: To report a novel surgical approach for the scleral fixation of the Rayner 620 H intraocular lens (IOL) with Gore-Tex suture and its outcomes at 6 months postoperatively. METHODS: 19 consecutive patients who underwent novel surgical approach for the scleral fixation of Rayner 620 H IOL with Gore-Tex suture at Peking Union Medical College Hospital between June 2020 and June 2021 were included. Data on best-corrected visual acuity (BCVA), spherical equivalent, total astigmatism/axis, short-term and long-term complications, and corresponding management with a follow-up of 6 months were collected. RESULTS: Nineteen patients (11 men and 8 women) with a mean age of 62.7 ± 10.6 years were included. The median BCVA improved significantly from 0.90 ± 0.90 (Snellen 20/160) preoperatively to 0.20 ± 0.30 (Snellen 20/32) at postoperative 6 months follow-up (P < 0.001). The stratification of the accuracy of refractive outcomes was 53% of patients within ± 0.5 D and 84% of patients within ± 1.0 D of the refractive target. Corneal edema (n = 3, 16%) and increased intraocular pressure (IOP) (n = 4, 11%) were short-term complications. Long-term complications included increased IOP (n = 1, 5%), and macular edema (n = 1, 5%). CONCLUSION: The novel surgical approach for scleral fixation of the Rayner 620 H IOL with Gore-Tex suture is a reasonable option for patients who need secondary IOL placement without adequate capsular support.

Chinese Guideline on the Management of Polypoidal Choroidal Vasculopathy (2022).

Background In mainland China, patients with neovascular age-related macular degeneration (nAMD) have approximately an 40% prevalence of polypoidal choroidal vasculopathy (PCV). This disease leads to recurrent retinal pigment epithelium detachment (PED), extensive subretinal or vitreous hemorrhages, and severe vision loss. China has introduced various treatment modalities in the past years and gained comprehensive experience in treating PCV.Methods A total of 14 retinal specialists nationwide with expertise in PCV were empaneled to prioritize six questions and address their corresponding outcomes, regarding opinions on inactive PCV, choices of anti-vascular endothelial growth factor (anti-VEGF) monotherapy, photodynamic therapy (PDT) monotherapy or combined therapy, patients with persistent subretinal fluid (SRF) or intraretinal fluid (IRF) after loading dose anti-VEGF, and patients with massive subretinal hemorrhage. An evidence synthesis team conducted systematic reviews, which informed the recommendations that address these questions. This guideline used the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach to assess the certainty of evidence and grade the strengths of recommendations. Results The panel proposed the following six conditional recommendations regarding treatment choices. (1) For patients with inactive PCV, we suggest observation over treatment. (2) For treatment-na?ve PCV patients, we suggest either anti-VEGF monotherapy or combined anti-VEGF and PDT rather than PDT monotherapy. (3) For patients with PCV who plan to initiate combined anti-VEGF and PDT treatment, we suggest later/rescue PDT over initiate PDT. (4) For PCV patients who plan to initiate anti-VEGF monotherapy, we suggest the treat and extend (T&E) regimen rather than the pro re nata (PRN) regimen following three monthly loading doses. (5) For patients with persistent SRF or IRF on optical coherence tomography (OCT) after three monthly anti-VEGF treatments, we suggest proceeding with anti-VEGF treatment rather than observation. (6) For PCV patients with massive subretinal hemorrhage (equal to or more than four optic disc areas) involving the central macula, we suggest surgery (vitrectomy in combination with tissue-plasminogen activator (tPA) intraocular injection and gas tamponade) rather than anti-VEGF monotherapy. Conclusions Six evidence-based recommendations support optimal care for PCV patients' management.

Proteomic changes of aqueous humor in proliferative diabetic retinopathy patients treated with different intravitreal anti-VEGF agents.

Anti-VEGF-based treatment have been regularly used in recent years in proliferative diabetic retinopathy (PDR) patients. However, some of these patients fail to respond effectively to anti-VEGF. Given that VEGF is not the sole factor influencing PDR pathogenesis and that different anti-VEGF pharmaceuticals are likely to differentially impact these underlying pathophysiological processes, we performed a prospective analysis of the protein profiles of the aqueous humor (AH) in PDR patients before and after treatment with three intravitreal anti-VEGF drugs (ranibizumab, aflibercept, and conbercept) to assess and compare the short-term impacts of these agents. Liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomic methods were used to evaluate the AH protein profiles of PDR patients using paired pre- and 7 days post-anti-VEGF treatment samples (ranibizumab [IVR]: n = 10; conbercept [IVC]: n = 10; aflibercept [IVA]: n = 5). Gene ontology (GO) annotation, KEGG pathway analyses, and protein-protein interaction (PPI) networks were then used to explore the functional relevance of proteins that were differentially expressed between groups. Here, a total of 874 proteins from 25 patients (50 AH samples) were identified in the three patient groups. Different and common clusters of regulated proteins for each group were identified. We identified RARRES1, ALDH3A1, and RBP4 as being specifically regulated following treatment with all three tested anti-VEGF agents. We further found that VEGFR1, VEGFR2, APOM, hornerin, and HSP90B1 were differentially expressed in different anti-VEGF agent groups. In summary, we discovered that ALDH3A1 was a previously unreported protein that was related to angiogenesis and was differentially expressed in the three anti-VEGF treatment groups, suggesting that it may be a new target for PDR therapy. The described proteomic changes in the AH of PDR patients treated with different anti-VEGF agents provide novel targets which may explain the heterogeneity of anti-VEGF treatment responses in these patients, providing a robust foundation for future studies of PDR pathogenesis.

Application of a 3D-printed eye model for teaching direct ophthalmoscopy to undergraduates.

PURPOSE: This study aims to design an eye model that can simulate the fundus for teaching direct ophthalmoscopy and to evaluate its effectiveness. METHODS: We first used 3D printing materials to make an eye model and then randomly assigned 92 undergraduates into group A (model-assisted training group) and group B (traditional training group) to test our model. After the same training time, real patients were used to test the students, with 120 s as the examination time limit. We recorded the students' ability to clearly see the optic disk, the time to determine the cup-to-disk ratio, and whether they were correct. RESULTS: Forty-three students in group A (93.48%) successfully saw the fundus, while 21 in group B (45.65%) succeeded. The difference between the two groups was 47.83% (95% confidence interval, 29.59-66.07%, P < 0.0001). The median time to see the fundus was 29s (95% confidence interval 23-45 s) in group A, while an estimated minimum time in group B was 80 s, indicating that group A was significantly faster than group B (P < 0.0001). CONCLUSIONS: This 3D-printed eye model significantly improved the students' study interest, study efficiency, and study results and is worthy of being promoted.

Clinical characteristics of retinal arterial macroaneurysms and prognosis of different interventions.

PURPOSE: To estimate the clinical characteristics of retinal arterial macroaneurysms (RAM) and evaluate the prognosis of different interventions. METHODS: This study is a meta-analysis. The databases PubMed, EMBASE, and Ovid from inception to January 2021 were searched to identify the relevant studies. R software version 3.6.3 was used to perform the statistical analyses. Results in proportion with 95% confidence interval were calculated by means of Freeman-Tukey variant of arcsine square transformation. RESULTS: Sixty-nine studies involving 1332 patients were finally included. The pooling results indicated that 91% (95% CI [88 ~ 94%]) of the RAM patients were over sixty, 73% (95% CI [68 ~ 77%]) were female, and 73% (95% CI [66 ~ 79%]) have hypertension. By observation, the RAM closure rate was 64% (95% CI [39 ~ 86%]), the visual acuity (VA) improved in 55% (95% CI [40 ~ 71%]) of the patients, and the VA of 64% (95% CI [54 ~ 74%]) hemorrhagic versus 27% (95% CI [15 ~ 41%]) exudative patients improved significantly. By laser, the closure rate was 96% (95% CI [87 ~ 100%]), the VA improved in 73% (95% CI [65 ~ 80%]) of the patients, and the VA of 66% (95% CI [47 ~ 84%]) hemorrhagic versus 35% (95% CI [23 ~ 47%]) exudative patients improved significantly. By anti-VEGF, the closure rate was 98% (95% CI [93 ~ 100%]), the VA improved in 90% (95% CI [74 ~ 100%]) of the patients, and the VA of 58% (95% CI [18 ~ 94%]) hemorrhagic versus 67% (95% CI [31 ~ 96%]) exudative patients improved significantly. CONCLUSION: RAM are most commonly seen in the elderly with a marked female predominance and a strong association with hypertension. Patients receiving laser or anti-VEGF treatments get higher closure rate and better visual prognosis than those with observation alone. Hemorrhagic RAM have a better visual prognosis by observation or laser treatment, while exudative RAM have a better visual prognosis by anti-VEGF treatment.

Automated detection of severe diabetic retinopathy using deep learning method.

PURPOSE: The purpose of this study is to develop and validate the intelligent diagnosis of severe DR with lesion recognition based on color fundus photography. METHODS: The Kaggle public dataset for DR grading is used in the project, including 53,576 fundus photos in the test set, 28,101 in the training set, and 7,025 in the validation set. We randomly select 4,192 images for lesion annotation. Inception V3 structure is adopted as the classification algorithm. Both 299 × 299 pixel images and 896 × 896 pixel images are used as the input size. ROC curve, AUC, sensitivity, specificity, and their harmonic mean are used to evaluate the performance of the models. RESULTS: The harmonic mean and AUC of the model of 896 × 896 input are higher than those of the 299 × 299 input model. The sensitivity, specificity, harmonic mean, and AUC of the method with 896 × 896 resolution images as input for severe DR are 0.925, 0.907, 0.916, and 0.968, respectively. The prediction error mainly occurs in moderate NPDR, and cases with more hard exudates and cotton wool spots are easily predicted as severe cases. Cases with preretinal hemorrhage and vitreous hemorrhage are easily identified as severe cases, and IRMA is the most difficult lesion to recognize. CONCLUSIONS: We have studied the intelligent diagnosis of severe DR based on color fundus photography. This artificial intelligence-based technology offers a possibility to increase the accessibility and efficiency of severe DR screening.

THREE-DIMENSIONAL HEAD-UP DISPLAY VERSUS STANDARD OPERATING MICROSCOPE FOR VITRECTOMY SURGERY: A Systematic Review and Meta-analysis.

PURPOSE: To evaluate the effects of vitrectomy with three-dimensional head-up display (3D HUD) versus standard operating microscopy (SOM) for retinal diseases. METHODS: The PubMed, Cochrane Library, and Embase databases were comprehensively searched to identify studies that compared 3D HUD versus SOM in vitrectomy for retinal diseases (PROSPERO protocol CRD42021265827). The primary outcomes are duration of surgical time, postoperative best-corrected visual acuity, endoillumination levels, and intraoperative complications. The secondary outcomes are reattachment rate of rhegmatogenous retinal detachment, macular hole closure rate, and the like. RESULTS: Fifteen studies of 2,889 eyes were included. Compared with SOM, 3D HUD vitrectomy took a longer surgical time (weighted mean difference = 1.48; 95% confidence interval, 0.13-2.82), but it needed lower endoillumination levels (weighted mean difference = -16.04, 95% confidence interval, -18.33 to -13.75) than SOM. There were no significant differences in the postoperative best-corrected visual acuity, intraoperative complications, reattachment rate of rhegmatogenous retinal detachment, or closure rate of macular hole. CONCLUSION: Our results suggested that 3D HUD provides lower retinal illumine toxicities but with a longer surgical time. The surgical results and complications of vitrectomy were equally comparable for 3D HUD and SOM.

CLINICAL CHARACTERISTICS OF EALES DISEASE AND THE EFFICACY OF DIFFERENT INTERVENTIONS FOR NEOVASCULAR COMPLICATIONS.

PURPOSE: To evaluate clinical features and manifestations of Eales disease and the efficacy of different interventions. METHODS: The databases PubMed, EMBASE, and Ovid from inception until February 2021 were searched. Pooled analyses included 1) presenting features, 2) symptoms and signs, and 3) postoperative vision outcomes and complications. Statistical analyses were conducted with R software version 3.6.3. RESULTS: Forty-seven studies involving 3,557 patients and 4,959 eyes were included. The pooling results showed that Eales disease was male dominated (94%), bilateral involvement (64%), and mainly occurred in adolescents. Approximately 83% of patients were positive in Mantoux test, and 31% of patients have vitreous tap polymerase chain reaction positive for tuberculosis genome. More than half of the patients had decreased vision at the first clinic visit. The common signs of Eales disease included sclerotic vessels (83%), neovascularization of retina elsewhere (64%) and periphlebitis (51%). Macular changes could be detected in 24% of patients. The most common complication was vitreous hemorrhage, followed by cataracts and retinal detachment. Photocoagulation was directed at nonperfusion or neovascularization areas, with a decrease in the incidence of later pars plana vitrectomy (19%). Anti-vascular endothelial growth factor treatment was suggested for vitreous hemorrhage, which could achieve high visual acuity improvement rate (82%) while increasing the possibility of retinal detachment (18%). Pars plana vitrectomy was indicated in cases with persistent vitreous hemorrhage or retinal detachment, with 56% of patients obtaining visual improvement. Still, 17% of patients needed a second pars plana vitrectomy, mainly because of recurrent vitreous hemorrhage or retinal detachment. CONCLUSION: Eales disease most commonly affects young men. It has diverse clinical features, and management should be based on the progression of the disease.

Observation, laser photocoagulation or anti-VEGF therapy in the management of retinal arterial macroaneurysms.

BACKGROUND: To explore the efficacy of observation, laser photocoagulation, and anti-VEGF in the management of retinal arterial macroaneurysm (RAM). METHODS: We retrospectively included patients diagnosed with RAM at the Peking Union Medical College Hospital (PUMCH) from 2003 to 2021, and comprehensively reviewed cases documented in the literature from multiple databases (PROSPERO protocol CRD42022310417). Patients were categorized into 3 groups: the observation group, anti-VEGF group, and laser photocoagulation group. LogMAR visual acuity (VA) and central retinal thickness (CMT) at the end of the follow-up were analyzed. RESULTS: A total of 14 patients from the PUMCH and 210 patients from the literature review were included. VA and CMT in patients who underwent observation, laser photocoagulation, and anti-VEGF therapies were significantly improved from baseline (p < 0.05), with changes in LogMAR VA improved by -0.34 ± 0.68, -0.17 ± 0.58, and -0.45 ± 0.62 and changes in CMT improved by -148.26 ± 138.99 µm, -185.61 ± 130.37 µm, and -287.45 ± 171.87 µm, respectively. Subgroup analysis revealed that anti-VEGF therapy was used in patients with worse VA than patients who underwent laser photocoagulation (p = 0.010), but achieved better improvement in VA than the laser photocoagulation group (p = 0.049). Patients treated with anti-VEGF also had thicker CMT than the observation group (p = 0.013), and experienced better changes in CMT than the observation, as well as laser photocoagulation groups (p = 0.005; p = 0.047). CONCLUSION: Observation, anti-VEGF, and laser photocoagulation are effective therapeutic methods for the management of RAM, and anti-VEGF therapy is intended to better improve patients with severe VA and CMT.

Development and quantitative assessment of deep learning-based image enhancement for optical coherence tomography.

PURPOSE: To develop a deep learning-based framework to improve the image quality of optical coherence tomography (OCT) and evaluate its image enhancement effect with the traditional image averaging method from a clinical perspective. METHODS: 359 normal eyes and 456 eyes with various retinal conditions were included. A deep learning framework with high-resolution representation was developed to achieve image quality enhancement for OCT images. The quantitative comparisons, including expert subjective scores from ophthalmologists and three objective metrics of image quality (structural similarity index measure (SSIM), peak signal-to-noise ratio (PSNR) and contrast-to-noise ratio (CNR)), were performed between deep learning method and traditional image averaging. RESULTS: With the increase of frame count from 1 to 20, our deep learning method always obtained higher SSIM and PSNR values than the image averaging method while importing the same number of frames. When we selected 5 frames as inputs, the local objective assessment with CNR illustrated that the deep learning method had more obvious tissue contrast enhancement than averaging method. The subjective scores of image quality were all highest in our deep learning method, both for normal retinal structure and various retinal lesions. All the objective and subjective indicators had significant statistical differences (P < 0.05). CONCLUSION: Compared to traditional image averaging methods, our proposed deep learning enhancement framework can achieve a reasonable trade-off between image quality and scanning times, reducing the number of repeated scans.

Using artificial intelligence reading label system in diabetic retinopathy grading training of junior ophthalmology residents and medical students.

PURPOSE: Evaluate the efficiency of using an artificial intelligence reading label system in the diabetic retinopathy grading training of junior ophthalmology resident doctors and medical students. METHODS: Loading 520 diabetic retinopathy patients' colour fundus images into the artificial intelligence reading label system. Thirteen participants, including six junior ophthalmology residents and seven medical students, read the images randomly for eight rounds. They evaluated the grading of images and labeled the typical lesions. The sensitivity, specificity, and kappa scores were determined by comparison with the participants' results and diagnosis gold standards. RESULTS: Through eight rounds of reading, the average kappa score was elevated from 0.67 to 0.81. The average kappa score for rounds 1 to 4 was 0.77, and the average kappa score for rounds 5 to 8 was 0.81. The participants were divided into two groups. The participants in Group 1 were junior ophthalmology resident doctors, and the participants in Group 2 were medical students. The average kappa score of Group 1 was elevated from 0.71 to 0.76. The average kappa score of Group 2 was elevated from 0.63 to 0.84. CONCLUSION: The artificial intelligence reading label system is a valuable tool for training resident doctors and medical students in performing diabetic retinopathy grading.

Occurrence of Mycosporine-like Amino Acids (MAAs) from the Bloom-Forming Cyanobacteria Aphanizomenon Strains.

Mycosporine-like amino acids (MAAs) are widespread in various microbes and protect them against harsh environments. Here, four different Aphanizomenon species were isolated from severely eutrophic waterbodies, Lake Dianchi and the Guanqiao fishpond. Morphological characters and molecular phylogenetic analysis verified that the CHAB5919, 5921, and 5926 strains belonged to the Aphanizomenon flos-aquae clade while Guanqiao01 belonged to the Aphanizomenon gracile clade. Full wavelength scanning proved that there was obvious maximal absorption at 334 nm through purified methanol extraction, and these substances were further analyzed by HPLC and UPLC-MS-MS. The results showed that two kinds of MAAs were discovered in the cultured Aphanizomenon strains. One molecular weight was 333.28 and the other was 347.25, and the daughter fragment patterns were in accordance with the previously articles reported shinorine and porphyra-334 ion characters. The concentration of the MAAs was calibrated from semi-prepared MAAs standards from dry cells of Microcystis aeruginosa PCC7806 algal powder, and the purity of shinorine and porphyra-334 were 90.2% and 85.4%, respectively. The average concentrations of shinorine and porphyra-334 were 0.307−0.385 µg/mg and 0.111−0.136 µg/mg in Aphanizomenon flos-aquae species, respectively. And there was only one kind of MAAs (shinorine) in Aphanizomenon gracile species.,with a content of 0.003−0.049 µg/mg dry weight among all Aphanizomenon gracile strains. The shinorine concentration in Aphanizomenon flos-aquae was higher than that in Aphanizomenon gracile strains. The total MAAs production can be ranked as Aphanizomenon flos-aquae > Aphanizomenon gracile.