The AI revolution in glaucoma: Bridging challenges with opportunities.

Recent advancements in artificial intelligence (AI) herald transformative potentials for reshaping glaucoma clinical management, improving screening efficacy, sharpening diagnosis precision, and refining the detection of disease progression. However, incorporating AI into healthcare usages faces significant hurdles in terms of developing algorithms and putting them into practice. When creating algorithms, issues arise due to the intensive effort required to label data, inconsistent diagnostic standards, and a lack of thorough testing, which often limits the algorithms' widespread applicability. Additionally, the "black box" nature of AI algorithms may cause doctors to be wary or skeptical. When it comes to using these tools, challenges include dealing with lower-quality images in real situations and the systems' limited ability to work well with diverse ethnic groups and different diagnostic equipment. Looking ahead, new developments aim to protect data privacy through federated learning paradigms, improving algorithm generalizability by diversifying input data modalities, and augmenting datasets with synthetic imagery. The integration of smartphones appears promising for using AI algorithms in both clinical and non-clinical settings. Furthermore, bringing in large language models (LLMs) to act as interactive tool in medicine may signify a significant change in how healthcare will be delivered in the future. By navigating through these challenges and leveraging on these as opportunities, the field of glaucoma AI will not only have improved algorithmic accuracy and optimized data integration but also a paradigmatic shift towards enhanced clinical acceptance and a transformative improvement in glaucoma care.

Effect of intraocular pressure reduction on progressive high myopia (PHM study): study protocol of a randomised controlled trial.

BACKGROUND: In adult patients with high myopia (HM), progressive axial elongation poses a significant risk for the development of subsequent ocular complications that may lead to visual impairment. Effective strategies to reduce or prevent further axial elongation in highly myopic adult patients have not been available so far. Recent studies suggested that medically lowering intraocular pressure (IOP) may reduce axial elongation. OBJECTIVE: This clinical randomised controlled trial (RCT) aims to evaluate the efficacy of medical IOP reduction in adult patients with progressive HM (PHM). TRIAL DESIGN: Single-centre, open-label, prospective RCT. METHODS: This RCT will recruit 152 participants with PHM at the Zhongshan Ophthalmic Center (ZOC). Randomised in a ratio of 1:1, participants will receive IOP-lowering eyedrops (intervention group) or will be followed without treatment (control group) for 12 months. Follow-up visits will be conducted at 1, 6 and 12 months after baseline. Only one eye per eligible participant will be included for analysis. The primary outcome is the change in axial length (AL) within the study period of 12 months. Secondary outcomes include the incidence and progression of visual field (VF) defects, changes in optic disc morphology and incidence and progression of myopic maculopathy. Difference in AL changes between the two groups will be analysed using linear regression analysis. For the secondary outcomes, a multifactor Poisson regression within a generalised linear model will be used to estimate the relative risk of progression in VF defects and myopic maculopathy, and the rate of thinning in retinal nerve fibre layer and ganglion cell-inner plexiform will be assessed through Kaplan-Meier curves and log-rank tests. ETHICS AND DISSEMINATION: Full ethics approval for this trial has been obtained from the Ethics Committee of ZOC, Sun Yat-sen University, China (ID: 2023KYPJ110). Results of this trial will be disseminated through peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: NCT05850936.

Genetic association of TIE2 with diabetic retinopathy and diabetic macular edema.

PURPOSE: To evaluate the associations of the TIE2 gene with diabetic retinopathy (DR) and diabetic macular edema (DME). METHODS: This study included a Chinese cohort of 285 non-proliferative DR patients and 433 healthy controls. The DR patients were classified further into those with or without DME. Thirty haplotype-tagging single-nucleotide polymorphisms (SNPs) in TIE2 were genotyped using TaqMan technology. Associations of DR and subtypes were analyzed by logistic regression adjusted for age and sex. Stratification association analysis by sex was performed. RESULTS: TIE2 rs625767 showed a nominal but consistent association with DR [odds ratio (OR) = 0.71, P = 0.005] and subtypes (DR without DME: OR = 0.69, P = 0.016; DME: OR = 0.73, P = 0.045). SNP rs652010 was consistently associated with overall DR (OR = 0.74, P = 0.011) and DR without DME (OR = 0.70, P = 0.016), but not with DME. Moreover, SNPs rs669441, rs10967760, rs549099 and rs639225 showed associations with overall DR, whilst rs17761403, rs664461 and rs1413825 with DR without DME. In stratification analysis, three SNPs, rs625767 (OR = 0.62, P = 0.005), rs669441 (OR = 0.63, P = 0.006) and rs652010 (OR = 0.64, P = 0.007), were associated with DR in females, but not in males. Moreover, one haplotype T-T defined by rs625767 and rs669441 was significantly associated with DR in females only. CONCLUSIONS: This study revealed TIE2 as a susceptibility gene for DR and DME in Chinese, with a sex-specific association in females. Further validation should be warranted.

Efficacy and Safety of Surgical Peripheral Iridectomy, Goniosynechialysis, and Goniotomy for Advanced Primary Angle Closure Glaucoma Without Cataract: 1-Year Results of a Multicenter Study.

PRCIS: The combination of surgical peripheral iridectomy, goniosynechialysis, and goniotomy is a safe and effective surgical approach for advanced primary angle closure glaucoma without cataract. PURPOSE: To evaluate the efficacy and safety of surgical peripheral iridectomy (SPI), goniosynechialysis (GSL), and goniotomy (GT) in advanced primary angle closure glaucoma (PACG) eyes without cataract. PATIENTS AND METHODS: A prospective multicenter observational study was performed for patients who underwent combined SPI, GSL, and GT for advanced PACG without cataract. Patients were assessed before and after the operation. Complete success was defined as achieving intraocular pressure (IOP) between 6 and 18 mm Hg with at least a 20% reduction compared with baseline, without the use of ocular hypotensive medications or reoperation. Qualified success adopted the same criteria but allowed medication use. Factors associated with surgical success were analyzed using logistic regression. RESULTS: A total of 61 eyes of 50 advanced PACGs were included. All participants completed 12 months of follow-up. Thirty-six eyes (59.0%) achieved complete success, and 56 eyes (91.8%) achieved qualified success. Preoperative and postsurgical at 12 months mean IOPs were 29.7±7.7 and 16.1±4.8 mm Hg, respectively. The average number of ocular hypotensive medications decreased from 1.9 to 0.9 over 12 months. The primary complications included IOP spike (n=9), hyphema (n=7), and shallow anterior chamber (n=3). Regression analysis indicated that older age (odds ratio [OR]=1.09; P =0.043) was positively associated with complete success, while a mixed angle closure mechanism (OR=0.17; P =0.036) reduced success rate. CONCLUSIONS: The combination of SPI, GSL, and GT is a safe and effective surgical approach for advanced PACG without cataract. It has great potential as a first-line treatment option for these patients.

Impact of Peripheral Anterior Synechiae on the Outcome of Combined Phacoemulsification, Goniosynechialysis, and Goniotomy for Primary Angle Closure Glaucoma and Cataract: A Multicenter Observational Study.

PRCIS: The combination of phacoemulsification, goniosynechialysis and goniotomy is an effective treatment for primary angle closure glaucoma patients with cataract, and this is not linked to the extent of preoperative peripheral anterior synechiae. PURPOSE: To evaluate the impact of the extent of peripheral anterior synechiae (PAS) on the effectiveness and safety of combined phacoemulsification (PEI), goniosynechialysis (GSL), and goniotomy (GT) in eyes with primary angle closure glaucoma (PACG) and cataract. PATIENTS AND METHODS: This study included patients diagnosed with PACG and cataracts who underwent combined PEI and 120 degrees GSL plus GT (PEI+GSL+GT) between April 2020 and October 2022 at 10 ophthalmic institutes. Eligible patients were divided into 3 groups based on the extent of PAS: 180°≤PAS<270°, 270°≤PAS<360°, and PAS=360°. Data on intraocular pressure (IOP), the number of ocular hypotensive medications, and complications were collected and compared. The study defined complete success as postoperative IOP within the 6-18 mm Hg range and a 20% reduction from baseline without the use of topical medications. Qualified success was defined in the same way as complete success, but it allowed for the use of ocular hypotensive medications. RESULTS: Three hundred four eyes of 283 patients were included. The mean follow-up was 12.50±1.24 months. All groups experienced a significant reduction in IOP after the surgery ( P <0.05). There were no significant differences in final IOP, number of medications, and cumulative complete and qualified success rates among the 3 groups ( P >0.05). The groups with 270°≤PAS<360°had a higher frequency of hyphema compared with 180°≤PAS<270° ( P = 0.044). CONCLUSIONS: PEI+GSL+GT has proven to be an effective treatment for PACG with cataracts over a 1 year period. However, the outcome was not correlated with the preoperative extent of PAS.

Phacogoniotomy versus phacotrabeculectomy for advanced primary angle-closure glaucoma with cataract: A randomized non-inferiority trial.

PURPOSE: To investigate the effectiveness and safety of phacogoniotomy versus phacotrabeculectomy (PVP) among patients with advanced primary angle-closure glaucoma (PACG) and cataracts. DESIGN: Multicenter, randomized controlled, non-inferiority trial. METHODS: A total of 124 patients (124 eyes) with advanced PACG and cataracts were enrolled, with 65 in the phacogoniotomy group and 59 in the phacotrabeculectomy group. Patients were followed up for 12 months with standardized evaluations. The primary outcome was the reduction in intraocular pressure (IOP) from baseline to 12 months postoperatively, of which a non-inferiority margin of 4 mmHg was evaluated. Secondary outcomes included the cumulative surgical success rate, postoperative complications, and changes in the number of glaucoma medications. RESULTS: After 12 months, phacogoniotomy demonstrated non-inferiority to phacotrabeculectomy in terms of IOP reduction, with mean IOP reductions of - 26.1 mmHg and - 25.7 mmHg (P = 0.383), respectively, from baseline values of around 40 mmHg. Both groups experienced a significant reduction in the mean number of medications used postoperatively (P < 0.001). The cumulative success rate was comparable between the groups (P = 0.890). However, phacogoniotomy had a lower rate of postoperative complications and interventions (12.3% and 4.6%) compared to phacotrabeculectomy (23.7% and 20.3% respectively). The phacogoniotomy group reported shorter surgery time (22.1 ± 6.5 vs. 38.8 ± 11.1 min; P = 0.030) and higher quality of life (EQ-5D-5 L) improvement at 12 months (7.0 ± 11.5 vs. 3.0 ± 12.9, P = 0.010) than the phacotrabeculectomy group. CONCLUSIONS: Phacogoniotomy was non-inferior to phacotrabeculectomy in terms of IOP reduction for advanced PACG and cataracts. Additionally, phacogoniotomy provided a shorter surgical time, lower postoperative complication rate, fewer postoperative interventions, and better postoperative quality of life.

Optic neuropathy in high myopia: Glaucoma or high myopia or both?

Due to the increasing prevalence of high myopia around the world, structural and functional damages to the optic nerve in high myopia has recently attracted much attention. Evidence has shown that high myopia is related to the development of glaucomatous or glaucoma-like optic neuropathy, and that both have many common features. These similarities often pose a diagnostic challenge that will affect the future management of glaucoma suspects in high myopia. In this review, we summarize similarities and differences in optic neuropathy arising from non-pathologic high myopia and glaucoma by considering their respective structural and functional characteristics on fundus photography, optical coherence tomography scanning, and visual field tests. These features may also help to distinguish the underlying mechanisms of the optic neuropathies and to determine management strategies for patients with high myopia and glaucoma.

Minimally Invasive Glaucoma Surgery: Latest Developments and Future Challenges.

The development of minimally invasive glaucoma surgeries (MIGSs) was intended to provide safe and modestly efficacious modalities for early intervention of mild-to-moderate glaucoma, with minimal trauma and rapid recovery. They were mainly ab interno procedures that reduce intraocular pressure by facilitating the aqueous outflow by bypassing the trabecular meshwork resistance, reinforcing the uveoscleral flow via the supraciliary space, and reducing aqueous production by the ciliary body. While the cumulating evidence helps shape the role of the available MIGS, the exponential new development and advancement in this field has expanded the territory of MIGS. Apart from developing subconjunctival MIGS filtration devices (Xen gel stent and PRESERFLO MicroShunt), there is a tendency to revisit the "traditional" MIGS for alternative use and to modify the procedures with consideration of the fundamental aqueous outflow physiology. Combined MIGS has also been suggested, based on the theory that their different mechanisms may provide additive or synergistic effects. The advancement of laser procedures is also promising and could supplement unmet needs along the glaucoma treatment algorithm. This review examines the broad array of MIGS, updates the recent findings, discusses their potential alternative applications, and explores future challenges.

Update on coronavirus disease 2019: Ophthalmic Manifestations and Adverse Reactions to Vaccination.

The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 was one of the most devastating public health issues in recent decades. The ophthalmology community is as concerned about the COVID-19 pandemic as the global public health community is, as COVID-19 was recognized to affect multiple organs in the human body, including the eyes, early in the course of the outbreak. Ophthalmic manifestations of COVID-19 are highly variable and could range from mild ocular surface abnormalities to potentially sight and life-threatening orbital and neuro-ophthalmic diseases. Furthermore, ophthalmic manifestations may also be the presenting or the only findings in COVID-19 infections. Meanwhile, global vaccination campaigns to attain herd immunity in different populations are the major strategy to mitigate the pandemic. As novel vaccinations against COVID-19 emerged, so were reports on adverse ophthalmic reactions potentially related to such. As the world enters a post-pandemic state where COVID-19 continues to exist and evolve as an endemic globally, the ophthalmology community ought to be aware of and keep abreast of the latest knowledge of ophthalmic associations with COVID-19 and its vaccinations. This review is a summary of the latest literature on the ophthalmic manifestations of COVID-19 and the adverse ophthalmic reactions related to its vaccinations.

Optic Nerve Head Abnormalities in Nonpathologic High Myopia and the Relationship With Visual Field.

PURPOSE: To describe the optic nerve head (ONH) abnormalities in nonpathologic highly myopic eyes based on swept-source optical coherence tomography (OCT) and the relationship with visual field (VF). DESIGN: Secondary analysis from a longitudinal cohort study. METHODS: Highly myopic patients without myopic maculopathy of category 2 or higher were enrolled. All participants underwent a swept-source OCT examination focused on ONH. We differentiated between 3 major types (optic disc morphologic abnormality, papillary/peripapillary tissue defect, and papillary/peripapillary schisis) and 12 subtypes of ONH abnormalities. The prevalence and characteristics of ONH abnormalities and the relationship with VF were analyzed. RESULTS: A total of 857 participants (1389 eyes) were included. Among the 1389 eyes, 91.86%, 68.61%, and 34.92% of them had at least 1, 2, or 3 ONH abnormalities, respectively, which corresponded to 29.55%, 31.79%, and 35.67% of VF defects, respectively. Among the 12 subtypes of the 3 major types, peripapillary hyperreflective ovoid mass-like structure, visible retrobulbar subarachnoid space, and prelaminar schisis were the most common, respectively. Perimetric defects corresponding to OCT abnormalities were more commonly found in eyes with peripapillary retinal detachment, peripapillary retinoschisis, and peripapillary hyperreflective ovoid mass-like structure. Glaucoma-like VF defects were more common in eyes with deep optic cups (28.17%) and with optic disc pit/pit-like change (18.92%). CONCLUSIONS: We observed and clarified the ONH structural abnormalities in eyes with nonpathologic high myopia. These descriptions may be helpful to differentiate changes in pathologic high myopia or glaucoma.

Outcomes of Goniotomy With or Without Secondary Intraocular Lens Implantation in Pediatric Glaucoma Following Cataract Surgery: A Prospective Pilot Study.

PURPOSE: To report the outcomes of a 120-degree goniotomy (GT) with or without secondary intraocular lens (IOL) implantation in glaucoma following cataract surgery (GFCS). DESIGN: Prospective, observational study. METHODS: Pediatric patients with GFCS who underwent standalone 120-degree GT or 120-degree GT combined with secondary IOL implantation (GT+IOL) from March 2022 to August 2022 at the Zhongshan Ophthalmic Center were recruited. Primary outcomes were intraocular pressure (IOP) and the number of ocular hypotensive medications. A secondary outcome was the surgical success rate. Success was defined as a postoperative IOP within the range of 5-21 mm Hg. Complete and qualified successes were defined, as the above, without and with ocular hypotensive medications, respectively. RESULTS: Thirty-two eyes of 22 patients were included. The mean age at the time of GT was 68.5 ± 29.3 months. The mean follow-up duration was 12.2 ± 2.3 months (9-15 mo). Mean IOP decreased from 30.9 ± 4.8 mm Hg on 2 (interquartile range = 1) medications at baseline to 15.8 ± 3.6 mm Hg on 0 (interquartile range = 1.5) medication at the latest visit in all eyes. The overall complete and qualified success rates were 68.8% and 90.6%, respectively. There were no significant differences in IOP, number of medications, and complete and qualified success rates between the standalone GT and GT+IOL groups at the latest follow-up at 9 months postoperatively. CONCLUSIONS: To reduce the need for additional surgery, 120-degree GT was a safe and effective surgical treatment for GFCS in children, which could be combined with secondary IOL implantation in aphakic eyes with GFCS.

Influence of Goniotomy Size on Treatment Safety and Efficacy for Primary Open-Angle Glaucoma: A Multicenter Study.

PURPOSE: To compare the efficacy and safety of 120-, 240-, and 360-degree goniotomy (GT) with or without phacoemulsification with intraocular lens implantation (PEI) for patients with primary open-angle glaucoma (POAG). DESIGN: Multicenter, retrospective, comparative, nonrandomized interventional study. METHODS: Patients diagnosed with POAG who underwent GT with or without PEI were included, and divided into 6 groups: 1) standalone 120-degree GT (120GT); 2) standalone 240-degree GT (240GT); 3) standalone 360-degree GT (360GT); 4) PEI + 120GT; 5) PEI + 240GT; and 6) PEI + 360GT. Data on intraocular pressure (IOP), the number of ocular hypotensive medications, and complications were collected and compared. Success was defined as a postoperative IOP within the range of 6 to 18 mm Hg and a 20% reduction from baseline without further glaucoma surgery. Complete success and qualified success were defined as the above without and with ocular hypotensive medications, respectively. RESULTS: Three hundred eight eyes of 231 patients were included with a mean follow-up of 14.4 ± 8.6 months (6.0-48.0 months). There were no significant differences in the reductions in IOP and number of medications and cumulative survival probability for complete and qualified success rates among the 3 groups of standalone GT and PEI + GT. The 360GT group had the highest proportion of hyphema with or without PEI. CONCLUSIONS: 120GT, 240GT, and 360GT with or without PEI showed similar efficacy in reducing IOP and medications used in POAG. 360GT with or without PEI was more likely to cause hyphema compared with 120GT or 240GT. 120GT with or without PEI was sufficient for treating POAG with or without cataract..

High Myopia Normative Database of Peripapillary Retinal Nerve Fiber Layer Thickness to Detect Myopic Glaucoma in a Chinese Population.

PURPOSE: To develop and validate the performance of a high myopia (HM)-specific normative database of peripapillary retinal nerve fiber layer (pRNFL) thickness in differentiating HM from highly myopic glaucoma (HMG). DESIGN: Cross-sectional multicenter study. PARTICIPANTS: A total of 1367 Chinese participants (2325 eyes) with nonpathologic HM or HMG were included from 4 centers. After quality control, 1108 eyes from 694 participants with HM were included in the normative database; 459 eyes from 408 participants (323 eyes with HM and 136 eyes with HMG) and 322 eyes from 197 participants (131 eyes with HM and 191 eyes with HMG) were included in the internal and external validation sets, respectively. Only HMG eyes with an intraocular pressure > 21 mmHg were included. METHODS: The pRNFL thickness was measured with swept-source (SS) OCT. Four strategies of pRNFL-specified values were examined, including global and quadrantic pRNFL thickness below the lowest fifth or the lowest first percentile of the normative database. MAIN OUTCOMES MEASURES: The accuracy, sensitivity, and specificity of the HM-specific normative database for detecting HMG. RESULTS: Setting the fifth percentile of the global pRNFL thickness as the threshold, using the HM-specific normative database, we achieved an accuracy of 0.93 (95% confidence interval [CI], 0.90-0.95) and 0.85 (95% CI, 0.81-0.89), and, using the first percentile as the threshold, we acheived an accuracy of 0.85 (95% CI, 0.81-0.88) and 0.70 (95% CI, 0.65-0.75) in detecting HMG in the internal and external validation sets, respectively. The fifth percentile of the global pRNFL thickness achieved high sensitivities of 0.75 (95% CI, 0.67-0.82) and 0.75 (95% CI, 0.68-0.81) and specificities of 1.00 (95% CI, 0.99-1.00) and 1.00 (95% CI, 0.97-1.00) in the internal and external validation datasets, respectively. Compared with the built-in database of the OCT device, the HM-specific normative database showed a higher sensitivity and specificity than the corresponding pRNFL thickness below the fifth or first percentile (P < 0.001 for all). CONCLUSIONS: The HM-specific normative database is more capable of detecting HMG eyes than the SS OCT built-in database, which may be an effective tool for differential diagnosis between HMG and HM. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Outcomes of Partial Versus Complete Goniotomy With or Without Phacoemulsification for Primary Open Angle Glaucoma: A Multicenter Study.

PRCIS: Goniotomy (GT) 120 degrees with or without phacoemulsification was sufficient to lower the intraocular pressure (IOP) and reduce hyphema for primary open angle glaucoma. PURPOSE: To compare the surgical outcomes and safety profiles of 120 degrees and 360 degrees GT with or without phacoemulsification cataract extraction and intraocular lens implantation (PEI) for primary open angle glaucoma. PATIENTS AND METHODS: This multicenter retrospective study consisted of 139 eyes and was divided into 4 groups: (1) 120 degrees GT, (2) 360 degrees GT, (3) PEI + 120 degrees GT, and (4) PEI + 360 degrees GT. IOP, number of topical hypotensive medications, and complications were recorded and evaluated at baseline and at the final visit. The complete and qualified success rate and their potential associated factors were also investigated. The effectiveness and safety profile of the surgery were compared between different subgroups. RESULTS: After a mean follow-up of 8.6 months, the IOP reduction was 13.2 ± 8.3 (38.8 ± 28.8%), 12.4 ± 8.3 (41.6 ± 18.2%), 12.8 ± 9.9 (39.4 ± 34.5%), and 13.8 ± 7.2 (46.0±17.1%) mm Hg in 120 degrees, 360 degrees, PEI + 120 degrees GT group, and PEI + 360 degrees GT, respectively. No significant difference was found in IOP, a decline of IOP from baseline, topical hypotensive medication, and complete or qualified success between either standalone 120 degrees versus 360 degrees GT, or PEI + 120 degrees versus PEI + 360 degrees GT (all P s > 0.05). The PEI + 120 degrees GT group had a lower final IOP than the 120 degrees GT group ( P = 0.0002) whereas there was no difference between PEI + 360 degrees GT and 360 degrees GT group ( P = 0.893). Both 360 degrees GT and PEI + 360 degrees GT group had a significantly higher incidence of hyphema than the 120 degrees GT and PEI + 120 degrees GT groups (all P s < 0.0001). CONCLUSIONS: GT of 120 or 360 degrees lowered IOP equally with or without cataract surgery, and hyphema was most commonly noted after complete GT. Partial GT alone or in combination with cataract surgery was an effective and safe approach to manage patients with open angle glaucoma.

Review on the Safety and Efficacy of Brolucizumab for Neovascular Age-Related Macular Degeneration From Major Studies and Real-World Data.

Frequent antivascular endothelial growth factor injections in neovascular age-related macular degeneration (nAMD) often lead to poor compliance and suboptimal outcomes. A longer-acting agent has been a pressing unmet need until recently. Brolucizumab, an antivascular endothelial growth factor agent, is a single-chain antibody fragment approved by the US Food and Drug Administration (FDA) on October 8, 2019, for treating nAMD. It delivers more molecules at equivalent volumes of aflibercept, thus achieving a longer-lasting effect. We reviewed literature published in English between January 2016 and October 2022 from MEDLINE, PubMed, Cochrane database, Embase, and Google scholar using the keywords: "Brolucizumab, real-world data, intraocular inflammation (IOI), safety, and efficacy". Brolucizumab showed reduced injection frequency, better anatomic outcomes, and noninferior vision gains compared with aflibercept in HAWK and HARRIER studies. However, post hoc studies on brolucizumab revealed a higher-than-expected incidence of IOI, leading to the early termination of 3 studies: MERLIN, RAPTOR, and RAVEN for nAMD, branch retinal vein occlusion, and central retinal vein occlusion, respectively. Contrastingly real-world data showed encouraging outcomes in terms of fewer IOI cases. The subsequent amendment of the treatment protocol resulted in reduced IOI. Thereafter US FDA approved its use in diabetic macular edema on June 1, 2022. Based on major studies and real-world data, this review shows that brolucizumab is effective for treating naive and refractory nAMD. The risk of IOI is acceptable and manageable, but proper preinjection screening and high-vigilance care of IOI are needed. More studies are warranted to evaluate further the incidence, best prevention, and treatment measures for IOI.