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A 63-year-old male patient presented with a four-month history of vision loss in the left eye and blurred vision in the right eye, the cause of which was not immediately apparent. The patient was initially diagnosed with uveitis in both eyes at the Department of Ophthalmology. Subsequently, the patient was diagnosed as central nervous system lymphoma at the Department of Brain Medicine and initiated a systemic treatment. However, due to the progressive deterioration of visual function, a further evaluation was performed at the Department of Ophthalmology. Based on the results of the vitreous fluid cytokine test, intraocular lymphoma was diagnosed in both eyes. Intravitreal methotrexate injections were administered for eight times and a notable improvement in visual acuity was achieved in both eyes.

Autophagic dysfunction-induced deterioration of the retinal microenvironment drives the progression of wet age-related macular degeneration (wAMD). The efficacy of single-target anti-VEGF antibodies in treating wAMD has long been suboptimal due to the intricate interplay between autophagy dysfunction, oxidative stress, and angiogenesis. Here, we introduce an intravitreal hydrogel depot, named Rab&Rapa-M@G, consisting of rapamycin-loaded microemulsion (Rapa-M, an mTOR inhibitor), ranibizumab (anti-VEGF antibody), and a thermosensitive hydrogel matrix. A single intravitreal injection of Rab&Rapa-M@G can sustainably deliver Rapa-M and ranibizumab to the retinal pigment epithelium for at least 14 days. This formulation significantly improves retinal autophagic flux homeostasis and reduces oxidative stress injury in wAMD mice by modulating the AMPK/mTOR/HIF-1α/VEGF and AMPK/ROS/HO-1/VEGF pathways. Consequently, it synergistically disrupts the "autophagic dysfunction-oxidative stress-angiogenesis" loop, leading to a remarkable reduction in choroidal neovascularization area and retinal damage compared to ranibizumab alone. Notably, the sequential administration of ranibizumab and Rab&Rapa-M@G further enhances the overall anti-wAMD efficacy, achieved through sequential delivery of Rab and Rapa, allowing for a more precise grasp of the treatment window. In conclusion, this hydrogel depot design, with its sequential and sustained delivery of mTOR inhibitors and anti-VEGF antibodies, offers a promising strategy for multi-target synergistic therapy in wAMD., Competing Interests: Declaration of competing interest No potential conflict of interest was reported by the authors., (Copyright © 2024. Published by Elsevier B.V.)

To evaluate the effectiveness of postoperative intravitreal bevacizumab (IVB) in preventing neovascular glaucoma (NVG) and identify associated risk factors in patients with proliferative diabetic retinopathy (PDR) undergoing phacovitrectomy. Patients with PDR who underwent phacovitrectomy were enrolled and categorized into two subgroups based on their postoperative treatment regimen: one group received IVB within 2 months following phacovitrectomy (Group 1); the other did not receive IVB during this period (Group 2). A comparative analysis evaluated the distinguishing characteristics of the two groups after 1:1 propensity score matching. Kaplan-Meier survival analysis was utilized to determine the incidence of NVG after phacovitrectomy. Multivariate analysis with the Cox proportional hazards model identified risk factors associated with NVG postphacovitrectomy. A total of 206 eyes of 206 patients were investigated in this study. NVG developed in 15 eyes (7.28%). The probabilities of NVG occurrence at 6, and 12 months following phacovitrectomy were 4.85%, and 7.28%, respectively. When comparing Groups 1 (n = 57) and 2 (n = 57), a significant difference was observed in the occurrence of NVG (P < 0.001). In Group 1, only one case of NVG (1.75%) were noted, whereas all other NVG cases occurred in Group 2 (9.39%). Male sex and high preoperative intraocular pressure (IOP) were associated with NVG occurrence following phacovitrectomy, and the administration of IVB within 2 months postphacovitrectomy demonstrated efficacy in preventing the development of NVG. Male sex and high preoperative IOP were associated with a higher incidence of NVG, and postoperative IVB had a protective effect against NVG occurrence., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

To evaluate the outcomes and predictive factors for fluid resolution following three loading injections of faricimab for neovascular age-related macular degeneration(AMD). This retrospective study included patients diagnosed with treatment-naïve neovascular AMD who received three monthly injections of faricimab. Changes in best-corrected visual acuity(BCVA) and central retinal thickness(CRT) following treatment were evaluated. The resolution of subretinal fluid(SRF), intraretinal fluid(IRF), and serous pigment epithelial detachment(PED) was also assessed. In addition, factors associated with complete resolution of SRF and IRF were investigated. A total of 69 patients were included in this study. BCVA significantly improved from a mean logarithm of minimal angle of resolution of 0.64 ± 0.41 at baseline to 0.47 ± 0.39 at 3 months (P < 0.001). CRT significantly decreased from 424.1 ± 155.5 μm at baseline to 266.3 ± 71.7 μm at 3 months (P < 0.001). At baseline, SRF was observed in 55 eyes (79.7%), IRF in 39 eyes(56.5%), and serous PED in 57 eyes(82.6%). By 3 months, the number of eyes showing these findings had decreased to 11 eyes(15.9%) for SRF, 6 eyes(8.7%) for IRF, and 10 eyes(14.5%) for serous PED. The presence of type 2 (88.2%) and type 3 (94.7%) macular neovascularization(MNV) was associated with a high incidence of complete resolution of SRF and IRF after treatment. Three loading injections of faricimab resulted in significant functional and anatomical improvements in treatment-naïve neovascular AMD, with a high rate of resolution of SRF, IRF, and serous PED. The anatomical effects were especially pronounced in cases of type 2 and type 3 MNV., Competing Interests: Declarations. Competing interests: Jae Hui Kim received lecture fees from Bayer, Novartis, Roche, Samsung Bioepis, and Chong Kun Dang Pharmaceutical Corp. Han Joo Cho received lecture fees from Bayer, Novartis, Roche. The remaining authors (H.Y.H., S.M.P., J.H.L., C.G.K., J.W.K.) declare no conflicts of interest., (© 2025. The Author(s).)

Background: This case report describes a rare case of Coats disease in adult female patient with preserved vision after intravitreal Aflibercept injection and laser photocoagulation., Case Presentation: A female patient of Asian Palestinian descent, aged 20, exhibited a progressive and painless deterioration in the vision of her left eye over a period of two weeks. She exhibited no additional ocular symptoms. Prior to her presentation, she had no notable medical history and her vision was normal in both eyes. Inferotemporal telangiectasia, sausage-like blood vessels with perivascular sheathing in the peripheral fundus, extensive exudate involving the macula, severe macular edema, and localized inferotemporal exudative retinal detachment were observed upon examination of the posterior segment of her left eye. Following this, optical coherence tomography (OCT) identified subretinal exudate, intraretinal and subretinal fluid. After establishing the diagnosis of stage 3 Coats' disease, the patient was treated with intravitreal Aflibercept (Eylea) injections and sectoral laser photocagulation. The third injection resulted in the absence of intraretinal and subretinal fluid by OCT, but the subretinal exudate remained unresolved. One month subsequent to the previous injection, FFA guided sectoral laser photoagulation was applied to the inferiotemporal ischemic area. The patient was subsequently monitored monthly, and her vision improved. Five months after treatment, her vision has improved to 0.7 (6/8.7) and she has remained stable ever since. At present, the patient is undergoing routine outpatient follow-up., Conclusion: Coats disease is an idiopathic, progressive disease that mostly affects male infants, yet adult cases have been documented. Our case and the existing body of literature indicate that adult individuals have a favorable visual prognosis in the small proportion of cases where this occurs. It appeared that the implementation of intravitreal therapies and increased use of lasers led to enhanced visual outcomes. It is recommended to perform lifelong follow-up to monitor for recurrences and complications., Competing Interests: Declarations. Ethics approval and consent to participate: Ethical approval was not sought for the present study because it is not reporting research findings. Consent for publication: Written informed consents for publication were obtained from the patient. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Current treatments for fundus disorders, such as intravitreal injections, pose risks, including infection and retinal detachment, and are limited in their ability to deliver macromolecular drugs across the blood‒retinal barrier. Although non-invasive methods are safer, their delivery efficiency remains suboptimal (<5%). We have developed a wearable electrodriven switch (WES) that improves the non-invasive delivery of macromolecules to the fundus. The WES system, which integrates an electrodriven drug delivery lens with a square wave generator, leverages electrical stimulation to enhance drug penetration through the sclera-choroid-retina pathway. In our study, WES achieved a delivery efficiency of 14% for immunoglobulin G, comparable to that of intravitreal injection (16%). Moreover, WES-enhanced anti-VEGF administration resulted in an 86% inhibition of choroidal neovascularization, and anti-PDL1 delivery inhibited choroidal melanoma growth more effectively than intravenous injections, with no adverse effects on ocular health. These findings suggest that WES holds transformative potential for the non-invasive treatment of chronic fundus diseases., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Purpose: This study aimed to identify a novel recombinant adeno-associated virus (rAAV) capsid variant that can widely transfect the deep retina through intravitreal injection and to assess their effectiveness and safety in gene delivery., Methods: By adopting the sequences of various cell-penetrating peptides and inserting them into the capsid modification region of AAV2, we generated several novel variants. The green fluorescent protein (GFP)-carrying variants were screened following intravitreal injection. Gene therapy experiments were conducted via intravitreal injection of rd1 mice. We validated the therapeutic effects utilizing the pupillary light reflex and visual cliff test. Assessment of retinal structure and Pde6b gene levels in rd1 mice after gene therapy further was confirmed through transcriptome sequencing to validate the gene therapy efficacy., Results: We observed enhanced transduction and penetration efficiency of the AAV variant AAV2.CPP.21 after intravitreal injection which can target all layers of the retinas. Normal doses of AAV2.CPP.21 administered via intravitreal injection achieved effective gene therapy for retinitis pigmentosa in rd1 mice, with no increased risk of transgenic leakage in peripheral organs., Conclusions: Our study identified another new, safe, and efficient AAV vector for gene therapy via intravitreal injection for retinal diseases. This new vector holds promise for clinical application and improvement of the efficacy of gene therapy for inherited retinal diseases.

Purpose: To evaluate the effectiveness of anterior subtenon triamcinolone (AST) injections in the management of refractory macular edema., Methods: This is a retrospective case series of consecutive eyes with refractory macular edema treated with AST at a single vitreoretinal surgeon's practice at Toronto Western Hospital, University of Toronto, Canada in 2018 to 2023. Refractory was defined as persistent macular edema with a central subfield thickness of 250 µ m or greater over a 24-week period, receiving at least four intravitreal antivascular endothelial growth factor injections. Vision outcomes and optical coherence tomography features for all eyes were compared for three visits pre-AST treatment and two visits post-AST treatment., Results: Ninety-three patients (119 eyes); diabetic macular edema (26%), and pseudophakic cystoid macular edema (74%), with a mean follow-up duration of 161 days were included. The presence of subretinal fluid ( P = 0.0013), central subfield macular thickness ( P < 0.0001), cube average thickness ( P = 0.0024), and macular cube volume ( P = 0.0017) significantly improved from pre-AST to post-AST treatment. Visual acuity also significantly improved from pre-AST treatment to post-AST treatment ( P < 0.0001). There was no significant change in the intraocular pressures from pre-AST to post-AST ( P = 0.7920), and no complications were noted throughout the follow-up period., Conclusion: The findings from this study suggest that AST injections show modest improvement in anatomical and functional outcomes and are safe for the treatment and management of refractory macular edema.

Purpose: To evaluate quantitative metrics of neovascularization lesions and choroidal vascular using swept-source optical coherence tomography angiography (SS-OCTA) in polypoidal choroidal vasculopathy (PCV) eyes, and investigate the relationship between imaging biomarkers and treatment outcomes of intravitreal anti-vascular endothelial growth factor (VEGF)., Methods: We retrospectively recruited 56 PCV patients. Choroidal features included subfoveal choroidal thickness (SFCT) and choroidal vascularity index (CVI). Quantitative metrics of neovascularization lesions included total vessel length (TVL), average vessel length (AVL), junction density (JD), total number of endpoints (TNE), and mean lacunarity (ML). We performed multivariate logistic and linear regression models to determine the prognostic factors for functional and morphological outcomes., Results: By comparison, functional good-responders had poorer best corrected visual acuity, higher TNE, and lower ML at baseline. Morphological good-responders had higher central retinal thickness, higher TNE, lower TVL and AVL, lower ML, lower SFCT and CVI. High-shrinkage of vessel area subgroup had higher JD and TNE, lower TVL and AVL, lower ML, lower SFCT and CVI. Multivariate analysis showed good morphological response was correlated with lower SFCT (P < 0.01). High-shrinkage subgroup was correlated with lower AVL (P = 0.017) and higher TNE (P < 0.01)., Conclusion: Quantitative metrics of neovascularization lesions and choroidal characteristics using SS-OCTA had the potential to be imaging biomarkers for predicting the response to anti-VEGF treatment. PCV lesions with higher TNE and lower AVL tended to appear higher shrinkage of vessel area, and lower SFCT was correlated with good morphological response., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Modern treatment protocols for retinal diseases involve frequent in-office monitoring with optical coherence tomography (OCT) and treatment with anti-vascular endothelial growth factor injections. Monthly injections may yield the greatest visual outcomes but are the most burdensome for patients and physicians, while as-needed injections may lead to undertreatment. Hybrid protocols, such as treat-and-extend (TREX) have been conceived to bridge this gap. Device-based home monitoring protocols for retinal disease may iterate further and allow more precise treatment tailored to individualized disease activity curves. Prior non-OCT home monitoring strategies have been developed with varying efficacy. These range from the ubiquitous but low-sensitivity Amsler grid to recent innovations such as the ForeseeHome preferential hyperacuity perimeter. Most recently, home OCT devices have been studied for remote monitoring, largely for use with age-related macular degeneration (AMD). Currently, the only Food and Drug Administration (FDA) approved device that utilizes OCT for monitoring retinal disease is the SCANLY Home OCT. Paired with an artificial intelligence (AI) algorithm that allows automated monitoring and alerting of retinal fluid volumes in AMD, SCANLY has demonstrated feasibility in limited trials to date, and a multicenter randomized controlled trial is currently underway to assess its efficacy in comparison to TREX regimens. Additional non-FDA-approved devices are being developed with varying degrees of study to date. Questions remain regarding its efficacy, real-world implementation, and financial considerations; nevertheless, home OCT has the potential to address many current barriers in retinal care, including travel and treatment burdens, while facilitating increased treatment precision., Competing Interests: C.Y.W. discloses the following relationships outside of the submitted work: Allergan/AbbVie, Alcon, Apellis Pharmaceuticals, Alimera Sciences, DORC, Novartis, Genentech, Regeneron, REGENXBIO, Astellas/Iveric Bio, EyePoint (consultant); DRCR Retina Network, Alimera Sciences, AGTC (research); Springer Publishers (royalties). The remaining authors declare that they have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To present a case of autosomal recessive bestrophinopathy (ARB) complicated by intraretinal fluid and subretinal fluid, successfully managed with navigated subthreshold micropulse laser (SML) treatment., Obervations: A 25-year-old female was referred to our clinic by her ophthalmologist due to a diagnosis of reduced vision in both eyes. The patient presented with a visual acuity of 0.9 logMAR in both eyes. Structural optical coherence tomography (OCT) revealed bilateral intraretinal fluid (IRF) and subretinal fluid (SRF), while OCT angiography (OCT-A) demonstrated bilateral macular neovascularization (MNV). Following the initiation of intravitreal therapy with anti-VEGF agents, administered via monthly injections for one year, we observed no improvement in visual acuity or resolution of IRF and SRF. SML treatment was administered to both eyes in the macular region. At the 3-month follow-up visit, OCT revealed complete resolution of IRF in the right eye and partial resolution of IRF in the left eye, and best-corrected visual acuity (BCVA) improved from 0.9 logMAR to 0.7 logMAR., Conclusions and Importance: In our case, SML emerges as a promising treatment modality for patients with ARB complicated by MNV who exhibit poor response to anti-VEGF therapy. However, further prospective studies with longer follow-up periods and larger cohorts are warranted to confirm the optimal treatment strategy in ARB., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: To describe a case of full thickness macular hole after intravitreal brolucizumab injection in neovascular age-related macular degeneration, which has not been reported to date., Case Description: A 65-year-old male patient received brolucizumab intravitreal injection therapy for neovascular macular degeneration of the right eye. He received multiple intravitreal anti-VEGF injections on a pro re nata regimen and developed a full thickness macular hole., Outcome: Surgical treatment was performed with pars plana vitrectomy of the right eye. Full thickness macular hole was successfully treated., Conclusion: Although a full thickness macular hole following intravitreal brolucizumab injection is an uncommon complication, it requires caution., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: To present a case of a patient with bilateral wet age-related macular degeneration who was unilaterally treated with intravitreal aflibercept injections (IAIs) and the disease status in the fellow eye ameliorated after an IAI., Methods: Retrospective case report., Results: A 72-year-old woman was diagnosed with wet and dry age-related macular degeneration in her right eye and left eye, respectively. In the right eye, treatment strategy comprised three monthly IAIs, followed by reinjections according to need, whereas optical coherence tomography scans were performed before IAIs. One month after the second IAI, subretinal fluid developed in the left eye. One week later, an IAI was applied in the right eye; 2 days later, the disease status in the left eye was assessed by fluorescein angiography and optical coherence tomography. Surprisingly, in the left eye, subretinal fluid completely resolved and fluorescein angiography did not detect leakage, highlighting the absence of an active choroidal neovascularization. The short interval between IAI and the resolution of exudative phenomena in the other eye is suggestive of a beneficial effect in the contralateral eye., Conclusion: In this article, we showed that an IAI had an effect to the fellow untreated eye. Our observation is consistent with active aflibercept in the systemic circulation. To the best of our knowledge, no other report in the literature has demonstrated this effect of aflibercept in wet age-related macular degeneration.

Recent developments in treatments for both forms of advanced age-related macular degeneration (AMD) have led to the approval of multiple agents and modalities within the last few years. Five new medications for both neovascular AMD (nAMD) and geographic atrophy (GA) secondary to nonexudative AMD (neAMD) have been FDA-approved within the last 5 years, along with a new device designed for sustained drug delivery for nAMD. In nAMD, the newest agents approved by the FDA are brolucizumab (Novartis Pharmaceuticals, Basel, Switzerland), faricimab (F. Hoffman-La Roche, Basel, Switzerland), aflibercept 8 mg (Regeneron Pharmaceuticals, Tarrytown, NY, USA), and a new device in the port delivery system with ranibizumab (Genentech, San Francisco, CA, USA). The first agents FDA-approved for GA secondary to neAMD are pegcetacoplan (Apellis Pharmaceuticals, Waltham, MA, USA) and avacincaptad pegol (Iveric Bio, Parsippany, NJ, USA). Evaluation of safety in both clinical trials and the real-world has been of paramount importance after the approval of these newest agents to understand their effects in real patients. Real-world data, as demonstrated in both registrational studies along with retrospective chart review studies, has shown to be an important factor in the implementation of newer drugs, along with the treatment decisions that physicians choose to make regarding their dosing and follow-up. This review article discusses the safety of the most recently approved FDA as seen in both clinical trials and real-world studies., Competing Interests: I.K. reports other from REGENXBIO INC, outside the submitted work; paid summer internship. A.A.A. reports other from REGENXBIO INC., outside the submitted work; paid summer internship. H.K. reports other from Genentech, outside the submitted work; paid summer internship. Dr G.M.G. reports personal fees from REGENXBIO. Dr A.K. reports personal fees from AbbVie, grants and personal fees from Adverum Biotechnologies, personal fees from Alcon, personal fees from Amgen, personal fees from Annexin, personal fees from Annexon, grants and personal fees from Apellis Pharmaceuticals, grants, financial interest, and personal fees from Aviceda Therapeutics, personal fees from Beacon Therapeutics, personal fees from Clearside Biomedical, personal fees from Complement Therapeutics, grants and personal fees from Genentech, grants and personal fees from Gyroscope Therapeutics, personal fees from i-Lumen Scientific, grants and personal fees from Iveric Bio, grants and personal fees from Janssen Pharmaceuticals, grants from personal fees from Kodiak Sciences, personal fees from Kriya Therapeutics, personal fees from Nanoscope, personal fees from Novartis, grants and personal fees from Ocular Therapeutix, grants, financial interest, and personal fees from Oculis, personal fees from Ocuphire, grants and personal fees from OcuTerra, personal fees from Olive Biopharma, grants, financial interest and personal fees from Opthea, grants and personal fees from Oxular, grants and personal fees from Oxurion, personal fees from Perfuse, personal fees from Ray Therapeutics, financial interest and personal fees from Recens Medical, personal fees from Regeneron Pharmaceuticals, grants, financial interest, and personal fees from Regenexbio, personal fees from Revive, financial interest and personal fees from RevOpsis, grants and personal fees from Roche, personal fees from Sanofi, personal fees from Stealth BioTherapeutics, personal fees from Thea Pharma, grants and personal fees from Unity Biotechnology, grants from personal fees from Vanotech, financial interest and personal fees from Vial, grants from Aviceda, grants from Alexion, grants from 4DMT, grants from Eyepoint, grants from Exegenesis, grants from Neurotech, financial interest from PolyPhotonix. The remaining authors declare that they have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To compare the efficacy of brolucizumab and aflibercept treatment in reducing the maximum thickness of pigment epithelial detachments (PEDs) and sub-retinal pigment epithelium (sub-RPE) fluid in patients with neovascular age-related macular degeneration in the HAWK and HARRIER studies., Design: HAWK and HARRIER were 96-week, prospective, randomized, double-masked, controlled, multicenter studies., Participants: A total of 1775 patients across 11 countries were included in the HAWK study, and 1048 patients across 29 countries were included in the HARRIER study., Intervention: After 3 monthly loading doses, brolucizumab-treated eyes received injections every 12 weeks or every 8 weeks if disease activity (DA) was detected. Aflibercept-treated eyes received fixed 8-week dosing., Main Outcome Measures: Maximum thickness of PEDs and sub-RPE fluid across the macula were assessed at baseline through week 96 in the brolucizumab- and aflibercept-treated patients and in the patient subgroups with DA at week 16 (matched in terms of injection number and treatment interval)., Results: At week 96, there were greater mean percentage reductions from baseline in maximum thickness of both PEDs and sub-RPE fluid in brolucizumab-treated patients vs. aflibercept-treated patients (PED: 19.7% [n = 336] vs. 11.9% [n = 335] in HAWK; 29.5% [n = 364] vs. 18.3% [n = 361] in HARRIER. Sub-RPE fluid: 75.4% vs. 57.3% in HAWK; 86.0% vs. 76.3% in HARRIER). A similar trend in mean percentage reductions was observed in patients with DA at week 16., Conclusions: This analysis shows that brolucizumab achieved greater reductions in PEDs and sub-RPE fluid thickness than aflibercept in HAWK and HARRIER., Trial Registration: ClinicalTrials.gov Identifiers: NCT02307682 (HAWK) and NCT02434328 (HARRIER)., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To demonstrate the treatment efficacy of intravitreal dexamethasone (DEX) implant in chronic recurrent/persistent central serous chorioretinopathy (CSC)., Design: Prospective, non-randomized, open-label study., Methods: In this study, subjects with chronic CSC without signs of choroidal neovascularization (CNV) received intravitreal DEX implant therapy. The primary outcome measure was the change in visual acuity. Changes in central macular thickness (CMT) and change in subfoveal choroidal thickness (SFCT) on optical coherence tomography (OCT), incidence of recurrent fluid, and safety of DEX implant were secondary outcome measures. Subjects were followed up for a minimum of 3 months after DEX implantation., Results: In total, 20 eyes of 20 subjects (mean age: 47 ± 9 years) with a median disease duration of 23.5 months were enrolled. With a single injection of DEX implant, a reduction in CMT was noted in 90% of eyes. Complete resolution of subretinal and intraretinal fluid was noted in 55% of eyes within 3 months of injection. A significant improvement in vision (mean Log MAR visual acuity: 0.66 ± 0.49 vs. 0.54 ± 0.45; P = 0.020), mean CMT (338 ± 110 microns to 238 ± 73 microns; P < 0.001) and SFCT (514 ± 95 microns to 445 ± 111 microns; P < 0.001) was noted over 3 months. Recurrent fluid was noted in 50% of eyes after a mean follow-up duration of 7 ± 4 months. Elevated intraocular pressure, managed by topical therapy, was noted in six eyes., Conclusion: The consistent improvement in visual acuity, fluid resolution, and reduction in choroidal thickness suggests a possible role for DEX implants in managing chronic CSC. A larger randomized trial is warranted., (Copyright © 2024 Indian Journal of Ophthalmology.)

Purpose: This study aims to quantify the volume of intraretinal fluid (IRF), subretinal fluid (SRF), and subretinal pigment epithelium (sub-RPE) fluid in treatment-naïve Type 3 macular neovascularization (MNV) eyes with age-related macular degeneration (AMD) and to investigate the correlation of these fluid volumes with visual acuity (VA) outcomes at baseline and following antivascular endothelial growth factor (VEGF) treatment., Design: Retrospective, clinical cohort study., Methods: In this study, we analyzed patients diagnosed with exudative AMD and treatment-naïve Type 3 MNV undergoing a loading dose of anti-VEGF therapy. Using a validated deep-learning segmentation strategy, we processed optical coherence tomography (OCT) B-scans to segment and quantify IRF (i.e., both in the inner and outer retina), SRF, and sub-RPE fluid volumes at baseline. The study correlated baseline fluid volumes with baseline and short-term VA outcomes postloading dose of anti-VEGF injections., Results: Forty-six eyes from 46 patients were included in this study. Visual acuity was 0.51 ± 0.30 LogMAR at baseline and 0.33 ± 0.20 LogMAR after the loading dose of anti-VEGF (P = .001). Visual acuity at the follow-up visit was 0.40 ± 0.17 LogMAR in patients with no complete resolution of retinal fluid and 0.31 ± 0.20 LogMAR in eyes without retinal fluid after treatment (P = .225). In the multivariable analysis, the IRF volume in the inner retina (P = .032) and the distance of the MNV from the fovea (P = .037) were predictors of visual acuity at baseline. The baseline IRF volume in the inner retina also predicted the visual acuity at follow-up (P = .023)., Conclusion: The present study highlights the fluid volume in the inner retina as a crucial predictor of short-term visual outcomes in Type 3 MNV, underscoring the detrimental effect of IRF on neuroretinal structures., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the efficacy and safety of high-dose intravitreal topotecan (IvitTopo) for recurrent retinoblastoma., Methods: There were 13 patients with recurrent retinoblastoma treated with high-dose IvitTopo (90 micrograms [ μ g]/0.18cc-100 µ g/0.20cc). The primary outcome measures were tumor control, globe salvage, and treatment complications., Results: At date first seen, median patient age was 9 months, and the affected eye was classified as International Classification of Retinoblastoma Group B (n = 2, 15%), Group C (n = 3, 23%), or Group D (n = 8, 62%) retinoblastoma with initial therapy of intravenous chemotherapy (n = 9, 69%) or intraarterial chemotherapy (n = 4, 31%). Recurrent tumor was detected at median 10 months as solid tumor (n = 3), subretinal seeds (n = 10), and/or vitreous seeds (n = 3) and high-dose IvitTopo (median three injections) delivered at monthly intervals. Additional chemotherapy was delivered by intraarterial (n = 8, 62%) or intravenous (n = 1, 8%) routes, and one eye received additional cryotherapy (n = 1, 8%). In three cases (23%), there was no additional therapy. At mean follow-up of 9 months, regression of solid tumor, subretinal seeds, and vitreous seeds was achieved in 12 cases (92%), and globe salvage was achieved in all cases (n = 13, 100%). Of those three eyes treated with high-dose IvitTopo alone, tumor control was initially achieved in all cases (100%), but one case that previously demonstrated massive vitreous seeding showed late recurrence of a solitary vitreous seed at 8 months. There were no complications., Conclusion: High-dose IvitTopo is an effective and safe therapy for recurrent retinoblastoma, in conjunction with other therapy, and possibly as a stand-alone therapy.

Purpose: To report 1-year anatomic and functional real-world outcomes of patients with treatment-intensive neovascular age-related macular degeneration (nAMD) switched to faricimab., Design: Retrospective multicenter cohort study., Subjects: Consecutive nAMD patients on 4-weekly treatment interval with either ranibizumab or aflibercept 2 mg in the last 3 visits within a treat-and-extend protocol (high treatment burden) before switch to faricimab at Moorfields Eye Hospital between September 5, 2022 and December 5, 2022., Methods: Patients with nAMD switched to faricimab were identified from electronic medical records and those who met criteria of high treatment burden were included. Data collected included preswitch and postswitch visual acuity (VA), treatment intervals, baseline macular morphology, central subfield thickness (CST), macular fluid status, and adverse events., Main Outcome Measures: Visual acuity, CST, presence of intraretinal fluid, subretinal fluid, and injection intervals over 1 year after switch to faricimab., Results: A total of 130 of 286 (45.5%) eyes met inclusion criteria of being switched due to high treatment burden and 117 were included in analysis. Before switch, these eyes received mean total number of injections of 33.4 ± 19.6 over a mean of 51.3 ± 34.9 months. Mean number of injections in 12 months preceding switch was 10.1 ± 1.6 and mean interval of the preceding 3 injections was 4.2 ± 0.3 weeks. Mean VA, CST, and percentage of patients with dry macula before switch were 66.0 ± 11.9 ETDRS letters, 259.6 ± 76.0 μm and 18.3% respectively. After switch, there was no statistical difference in mean VA throughout follow-up period. Mean CST statistically significantly reduced after the third faricimab injection and at 12 months by 20.0 μm (P = 0.035) and 22.1 μm (P = 0.041) respectively. Mean treatment intervals increased to 6.9 ± 2.3 weeks (P < 0.005) at 12 months with 42.9% and 11.4% of patients being on ≥8-weekly and ≥12-weekly treatment intervals, respectively., Conclusions: At 12 months, nAMD patients with previous record of high treatment burden when switched to faricimab maintained VAs and improved anatomic outcomes on extended treatment intervals. Physician bias is inherent in these types of observational studies so a prospective, randomized, controlled trial is recommended to validate these findings., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Retinopathy of prematurity (ROP) remains a significant health care concern in neonatal care as advances in neonatal intensive practices have improved the survival rates of premature infants. The management and screening of ROP have evolved significantly, with notable trends and advancements aimed at improving outcomes. The use of intravitreal antivascular endothelial growth factor injections has emerged as a prominent initial treatment for ROP in addition to laser photocoagulation. Screening practices have also seen enhancements, with a shift toward efficiency and tele-screening to optimize ROP management. This review aims to discuss available treatment and screening methods and explore new potential therapeutic tools for ROP., Competing Interests: N.A.P. is a consultant for Apellis, Alcon, Allergan, Atheneum, biogen, Dorc, Alimera, Eye Point, Genentech, Regenx Bio, Regeneron, Lifesciences, Guidepoint, Gerson Lehrman Group Inc., Kyoto Drug Company. The remaining authors declare that they have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Effective strategies for the neuroprotection and preservation of retinal ganglion cells (RGCs) remain elusive in the management of glaucoma. A spontaneous genetic model of glaucoma has been identified in cats and extensively characterized as a viable translational model, with eye size and anatomy similar to humans. In this study we sought to establish initial proof of concept for gene delivery to feline RGCs via intravitreal injection of AAV2 in normal cats. Pre-retinal, posterior vitreal injection of AAV2/2-CMV-GFP, was performed overlying the area centralis in 5 adult cats. Immunosuppressive oral prednisolone was administered perioperatively and gradually tapered over 6-10wks post-injection. Ophthalmic examination was performed pre- and post-injection. The GFP reporter expression and morphological effects of viral transduction on the retina were monitored in vivo using confocal scanning laser ophthalmoscopy (cSLO) and optical coherence tomography (OCT), respectively (Spectralis OCT-HRA, Heidelberg), at 1-2wk intervals over 6-10wks. Full-field electroretinograms (ERG) and visual evoked potentials (VEP) were recorded at baseline and post-injection. Retinas were examined by histology and immunolabeling for the RGC marker RBPMS and Müller cell and astrocyte marker SOX9, and GFP expression was examined in the retina, optic nerve (ON), optic tract and lateral geniculate nucleus (LGN). GFP + retinal cells and RGC axons were visualized by cSLO at 1-2 weeks post-injection. No retinal morphological changes were observed by OCT in vivo but 3/5 eyes exhibited mild retinal inflammation on histology. Retinal and ON function were preserved in injected eyes compared to baseline and untreated eyes. GFP expression was predominantly identified in RBPMS + RGC cells as well as SOX9 + Müller cells. GFP fluorescence was observed throughout RGC nerve fiber tract in the central visual pathway. Peak transduction in RGCs (up to ∼ 20 %) was observed in the regions with high GFP expression, but < 1 % of RGCs expressed GFP across the whole retina. Our data provide proof of concept that pre-retinal injection of AAV2/2 may represent a feasible platform for gene delivery to feline RGCs in vivo but highlight a need for further refinement to improve RGC transduction efficiency and control low-grade retinal inflammation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

We evaluate the pharmacokinetics, safety, and optimal dosages of intravitreal agents in silicone oil (SO)-filled eyes, addressing challenges in administering such therapies. We assessed the pharmacological properties and safety profiles of intravitreal drugs in SO-filled eyes, deriving conclusions and guidance from available literature and expert consensus. Preclinical data suggest comparable half-lives of anti-vascular endothelial growth factoragents in SO-filled eyes, but clinical evidence is mainly from case reports and small series. Available research prioritizes standard dosages, particularly for bevacizumab (1.25 mg), supported by stronger evidence than aflibercept (2 mg) or ranibizumab (0.5 mg). Intravitreal steroids, especially dexamethasone at 0.7 mg, show efficacy and safety, while evidence for fluocinolone acetonide at 0.19 mg is limited. Intravitreal methotrexate has been reported at the dosage of 250-400 μg, with keratitis as the primary expected side effect. Case reports indicate tolerability of standard dosages of antivirals (foscarnet 1.2-2.4 mg/0.1 mL, ganciclovir 4 mg/0.1 mL) and the antibiotic combination piperacillin/tazobactam (250 μg/0.1 mL). We offer guidance based on current, but limited, literature. Standard dosage of intravitreal agents should be carefully considered, along with close monitoring for potential side effects, which should be discussed with patients., Competing Interests: Declaration of Competing Interest None, (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate outcomes of eyes with postcataract surgery endophthalmitis that were managed without microbial cultures., Design: This retrospective, single-center comparative cohort study identified all cases of endophthalmitis after cataract surgery presenting between February 1, 2014, and November 1, 2022., Subjects: All eyes presenting with presumed endophthalmitis requiring in-office treatment with intravitreal antibiotics and either a vitreous or aqueous tap were included., Methods: Endophthalmitis cases were divided into the "culture group," if the vitreous or aqueous specimens were sent for microbiologic sampling, or into the "no culture group" if an aqueous or vitreous tap was performed but not sent for microbiologic sampling., Main Outcome Measures: Best-corrected visual acuity (VA) 12 months after endophthalmitis presentation, incidence of retinal detachment, and need for subsequent procedures., Results: Of the 232 endophthalmitis cases identified, 196 (85%) were in the "culture group" and 36 (15%) were in the "no culture group." At endophthalmitis presentation, eyes in the "culture group" had a mean (standard deviation [SD]) logarithm of the minimum angle of resolution (logMAR) VA (Snellen equivalent) of 2.14 (0.8) (20/2760) and mean (SD) logMAR VA in the "no culture group" was 1.93 (0.8) (20/1702) (P = 0.185). At 12-month follow-up, mean (SD) logMAR VA for the "culture group" was 0.80 (1.0) (20/126) and 0.41 (0.5) (20/50) in the "no culture group" (adjusted difference = 0.41, 95% confidence interval = -0.043 to 0.857, P = 0.076). Twenty of 196 (10%) eyes in the "culture group" developed secondary retinal detachments within 12 months of presentation compared with 0 in the "no culture group" (P = 0.045)., Conclusions: Eyes with endophthalmitis after cataract surgery managed without microbiologic cultures have similar visual outcomes to eyes managed with microbiologic cultures and may be less likely to develop secondary retinal detachments. This may be an acceptable strategy to manage endophthalmitis after cataract surgery when prompt access to a microbiologic facility is unavailable., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

Purpose: To report a case of punctate inner choroiditis (PIC) and subsequent choroidal neovascular membrane (CNVM) development in a young, high myope following vitreoretinal surgery for rhegmatogenous retinal detachment., Case Description: A 44-year-old male with high myopia underwent pars plana vitrectomy for subtotal retinal detachment in the left eye, followed by cataract extraction and silicone oil removal. Three years postoperatively, he presented with blurred vision, and fundus examination revealed PIC lesions at the posterior pole. Spectral-domain optical coherence tomography (SD-OCT) showed characteristic features of PIC, including hyperreflective nodule-like elevations, disrupted ellipsoid and interdigitation zones, retinal pigment epithelium (RPE) elevations and increased choroidal hyper transmission signals., Results: Initially, no treatment was initiated, and the patient was monitored. Three years later, the patient experienced further vision loss, and fundus examination showed progression of PIC lesions and new CNVM formation in the left eye. The patient was treated with systemic corticosteroids and an intravitreal anti-VEGF injection (Razumab ® 0.5 mg/0.05 ml). Three weeks after the intervention, SD-OCT showed regression of the CNVM, and the patient's visual symptoms improved., Conclusion: This case underscores the importance of long-term follow-up and timely intervention in managing PIC, especially in high myopes post-retinal surgery. Early identification and treatment with systemic corticosteroids and anti-VEGF therapy are crucial to preserving visual function and preventing severe complications like CNVM., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. To date, there are no effective therapies to counteract AMD towards the most severe stages characterised by a progressive loss of photoreceptors triggered by retinal pigmented epithelium dysfunction. Given their easy source and their high proliferative potential, Dental Pulp Stem Cells (DPSCs) are considered promising for regenerative medicine. The main advantage of DPSCs is related to their paracrine immunosuppressive and immunoregulatory abilities, including the capability to promote regeneration of damaged tissues. Recent studies demonstrated the therapeutic potential of DPSCs-conditioned media (CM) in neurodegenerative diseases. In addition, we have already shown a differential expression of some growth factors and cytokines in CM derived from DPSCs cultured in hypoxia and normoxia conditions., Aim: In this study we evaluated the capability of DPSCs-CM to counteract retinal degeneration in an animal model of AMD. DPSCs-CM were intravitreally injected the day before the exposure of albino rats to high intensity light (LD)., Results: We evaluated the retinal function, and we performed morphological and molecular analysis a week after the LD, in accordance with the well-established protocol of our light damage model. DPSCs-CM obtained from hypoxia (HYPO-CM) or normoxia (NORM-CM), were able to preserve the retinal function, to reduce the damaged area and to counteract the upregulation of key factors involved in retinal degeneration, like FGF-2. Furthermore, we demonstrated that neither conditioned media modified inflammatory activation, as shown by both microglia activation and GFAP upregulation, but in vitro studies demonstrated a significant effect of both CM to counteract oxidative stress, one of the main causes of AMD., Conclusion: Taken together, our study demonstrated that NORM-CM and HYPO-CM, albeit with a different chemical composition, could represent eligible candidates to counteract retinal degeneration in an animal model of AMD. Further studies are needed to obtain conditioned media with the best performance in term of retinal protection., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The age-related macular degeneration (AMD) field is witnessing promising advancements in therapeutic options. Breakthrough drugs such as pegcetacoplan and avacincaptad have been FDA-approved for dry AMD, marking a significant development as there were no treatment options until August 2023. While several antivascular endothelial growth factor (VEGF) inhibitors have been approved for wet AMD, challenges persist with the need for frequent dosing. New treatments such as gene therapy, cell therapy, WNT pathway agonists, complement inhibitors, and anti-VEGF combination drugs are under development to address these issues. These developments are exciting and hold promise for transforming the field of medicine, offering hope for improved outcomes and enhanced patient care in managing AMD., (Copyright © 2024 Indian Journal of Ophthalmology.)

Purpose: To objectively assess the immediate response to intravitreal treatment for macular edema and compare it across different agents., Methods: This retrospective, comparative study included patients with macular edema due to diabetic retinopathy (DME) or vein occlusion who were treated with intravitreal injections of either steroids (triamcinolone acetonide or dexamethasone sustained release implant) or anti-vascular endothelial growth factor antibodies (VEGF). The central retinal thickness (CRT) and the best corrected visual acuity (BCVA) were measured 1 day after the injection and compared with immediate pre-injection values., Results: There were 79 eyes (57 patients) including 51 eyes with DME, 18 with branch retinal vein occlusion edema (BRVO-ME), and 10 eyes with central retinal vein occlusion edema (CRVO-ME). The intravitreal agents were triamcinolone acetonide (TA)( n  = 15), dexamethasone sustained release implant (DEX)( n  = 22), ranibizumab ( n  = 19), and bevacizumab ( n  = 23). Statistically significant improvement in CRT was seen in all injection groups ( p  < 0.05) while improvement in mean BCVA was significant only in the TA group ( p  = 0.009). The mean change in CRT was maximum with steroids than with anti-VEGFs; viz. 159.47 µ in TA, 115.45 µ in DEX, 86.10 µ in ranibizumab, and 78.78 µ in bevacizumab group. Least amount of change was noted in the spongy type of macular edema (18.73 µ) while improvement in mean BCVA was statistically significant only in the cystoid group ( p  = 0.01)., Conclusions: Comparatively, steroid agents showed better immediate response to therapy than anti-VEGFs. Maximum reduction in central retinal thickness was seen following triamcinolone acetonide injection. Cystoid edema showed better immediate response than spongy retinal thickening., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: To describe the patient characteristics and clinical course of severe intraocular inflammation (IOI) following intravitreal injection (IVT) of faricimab., Design: Retrospective case series., Methods: Case series at a single French academic center (Dijon University Hospital) where 263 patients were treated with faricimab IVT between January 9, 2024 and May 7, 2024., Results: Over the 4-month period, a total of 1659 eyes (1338 patients) received anti-vascular endothelial growth factor (anti-VEGF) IVTs for a total of 3510 IVTs, of which 343 eyes (263 patients) received faricimab IVTs for a total of 971 IVTs. Overall, 6 pretreated eyes with neovascular age-related macular degeneration that were switched to faricimab developed severe unilateral IOI following faricimab IVT (1/162 injections [0.62%]), including 5 eyes presenting with a severe anterior and intermediate uveitis mimicking infectious endophthalmitis. All eyes were normotensive and presented with mild to moderate pain and predominantly moderate vitritis, associated with granulomatous keratic precipitates in 2 eyes and nonocclusive vasculitis in one eye. The clinical presentation, sterile vitreous sample culture, and rapid improvement with treatment made the diagnosis of infectious endophthalmitis unlikely. Four patients out of 6 did not recover their pre-IOI visual acuity, with an average visual loss of +0.2 logMAR. Two patients had positive antinuclear antibodies, including one with a history of cutaneous lupus., Conclusions: In this case series, we reported 6 cases of severe IOI after intravitreal faricimab over 4 months in a single French center with an estimated incidence rate of 0.6% per injection. Future real-world data will contribute to a better evaluation of the epidemiology of this rare inflammatory adverse event related to intravitreal faricimab., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: To characterize and monitor choroidal neovascularisation (CNV) secondary to angioid streaks (AS) using multimodal imaging and to compare the results with conventional fluorescein angiography (FA)., Methods: A total of 11 eyes with CNV secondary to AS were included in this retrospective study. Multimodal morphological and functional assessment, including spectral-domain optical coherence tomography (SD-OCT), spectral-domain optical coherence tomography angiography (SD-OCTA), and fundus autofluorescence (FAF), were used to assess for evidence of CNV activity and compared with conventional FA. Morphological features of CNV were analyzed and treatment was continuously monitored using SD-OCT and SD-OCTA., Results: Our results showed that SD-OCTA provided reliable results for the detection of secondary CNV in AS that were comparable to conventional FA. With SD-OCTA, a total of 13 CNVs were detected in 11 eyes and analyzed by means of outer retinal choriocapillaris depth (ORCC) segmentation and the corresponding B-scans. Twelve of the 13 CNVs were classified as active and therefore required treatment. For treatment monitoring during intravitreal therapy (IVT), SD-OCTA was found to be a valuable diagnostic tool over a mean follow-up of 76 weeks., Conclusions: Our study demonstrates that SD-OCTA can be routinely used to identify ill-defined CNV without dye-based angiography, especially in cases of CNV secondary to AS, where Bruch's membrane (BM) defects limit the diagnostic value of FA. Our results showed that non-invasive multimodal imaging facilitates sufficient CNV monitoring and treatment guidance. Further studies are warranted to provide more evidence in this rare retinal disease., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: To investigate the 12-month outcomes of ziv-aflibercept for neovascular age-related macular degeneration (nAMD) in eyes previously treated with aflibercept., Methods: Retrospective chart review of patients with nAMD previously treated with aflibercept for at least 12 months and subsequently transitioned to ziv-aflibercept between January 1, 2019, and December 31, 2022, for a period of at least 12 months. Participants were identified, and their clinical and imaging information was extracted from our electronic health records system. Data on best corrected visual acuity (BCVA), intraocular pressure, injection intervals, central retinal thickness (CRT), volume cube presence of subretinal fluid (SRF), and intraretinal fluid (IRF) were obtained. Main outcome measures included changes in BCVA, injection intervals, CRT, SRF, and IRF before and after 12 months of ziv-aflibercept treatment., Results: Fifty-four eyes of 44 patients were included in the study. After 12 months of ziv-aflibercept treatment, BCVA decreased by 0.84 ETDRS letters (P = 0.424) compared to BCVA at the last visit prior to conversion from aflibercept. Injection intervals decreased by 1.18 weeks (P = 0.489). CRT significantly decreased by 15.66 µm (P = 0.005). SRF was present initially in 31.5% of eyes and decreased to 22.2% (P = 0.125). IRF was present initially in 42.6% of eyes and decreased to 35.2% (P = 0.219)., Conclusion: Ziv-aflibercept demonstrated effectiveness in maintaining treatment outcomes in nAMD eyes previously treated with aflibercept. The treatment was well-tolerated with no reported adverse events. Ziv-aflibercept may be a cost-effective alternative and a potential solution to the financial burden associated with conventional anti-VEGF agents., (Copyright © 2024 Indian Journal of Ophthalmology.)

The management of intermediate and posterior uveitis poses a significant challenge of achieving adequate drug concentrations in the posterior segment over the chronic nature of the disease. Systemic agents seldom reach effective drug levels, and even with low maintenance or tapering doses, it is hard to avoid systemic toxicity. The use of intravitreal and periocular injections is often unable to prevent recurrences due to their short half-life. Since the emergence of intravitreal implants (Vitrasert, Retisert), it has become possible to circumvent these therapeutic challenges. A detailed review in the PubMed index yielded 155 articles, of which 22 were analyzed based on exclusion criteria. A recent shift from surgically sutured to minimally invasive injectable implants mainly indicated for noninfectious uveitis is evident from the literature. This review article also provides insights into dexamethasone (Ozurdex) and recent fluocinolone acetonide (Yutiq, Iluvien) implants with particular emphasis on their improved safety and efficacy. Dexamethasone implants favor the therapeutic goal of prevention of recurrences, whereas the use of fluocinolone implants helps to attain better visual outcomes due to their longer duration of action. Thus, the review provides recent literature supporting the role and indication of sustained release intravitreal implants in the management of noninfectious intermediate and posterior uveitis., (Copyright © 2024 Indian Journal of Ophthalmology.)

Purpose: To analyze cardiovascular and cerebrovascular adverse drug reactions (ADRs) after intravitreal anti-VEGF (aflibercept, bevacizumab, brolucizumab, and ranibizumab) treatment., Participants: VigiBase, a World Health Organization (WHO) global safety report database., Design: Pharmacovigilance study., Methods: The individual case safety reports (ICSRs) of cardiovascular and cerebrovascular ADRs after intravitreal anti-VEGF treatment were compared with those reported in the full database. From 2004 to 2023, there were 23 129 ADRs after intravitreal anti-VEGF therapy and 25 015 132 ADRs associated with any drug (full database)., Main Outcome Measures: The reporting odds ratio (ROR) and information components (ICs) were calculated, and the 95% lower credibility interval end point of the information component (IC 025 ) was used for disproportionate Bayesian reporting. Inter-drug comparisons were performed using the ratio of odds ratio (rOR)., Results: Compared with the full database, anti-VEGFs were associated with an increased reporting of myocardial infarction (IC 025 0.75; ROR: 1.78 [95% CI, 1.70-1.86]), angina pectoris (IC 025 0.53; ROR: 1.61 [95% CI, 1.47-1.77]), arrhythmias including atrial fibrillation, atrial flutter, ventricular fibrillation, supraventricular tachycardia (all IC 025 > 0, ROR>1), hypertension (IC 025 2.22; ROR: 4.91 [95% CI, 4.82-5.01]), and hypertensive crisis (IC 025 1.97; ROR: 4.49 [95% CI, 4.07-4.97]). Moreover, anti-VEGFs were associated with a higher reporting of cerebrovascular ADRs such as cerebral infarction (IC 025 4.34; ROR: 23.19 [95% CI, 22.10-24.34]), carotid artery stenosis (IC 025 1.85; ROR: 5.24 [95% CI, 3.98-6.89]), cerebral hemorrhage (IC 025 2.29; ROR: 5.38 [95% CI, 5.03-5.76]), and subarachnoid hemorrhage (IC 025 1.98; ROR: 4.81 [95% CI, 4.14-5.6]). Inter-drug comparison indicated that compared with ranibizumab, patients receiving aflibercept showed overall under-reporting of cardiovascular and cerebrovascular ADRs such as myocardial infarction (rOR 0.55 [95% CI, 0.49-0.52]), atrial fibrillation (rOR 0.28 [95% CI, 0.23-0.35]), cerebrovascular accident (rOR, 0.15 [95% CI, 0.14-0.17]), and cerebral hemorrhage (rOR, 0.51 [95% CI, 0.40-0.65])., Conclusions: In this pharmacovigilance case-noncase study, there was significantly increased reporting of cardiovascular and cerebrovascular ADRs after intravitreal anti-VEGF treatment. Although ranibizumab may exhibit superior systemic safety regarding its biological characteristics, it is crucial not to overlook the occurrence of cardiovascular and cerebrovascular ADRs considering its higher reporting rate than bevacizumab or aflibercept., Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2024. Published by Elsevier Inc.)

Age-related macular degeneration (AMD) is one of the leading causes of blindness in the world and anti-vascular endothelial growth factor (VEGF) injections have been the standard of care for the wet/neovascular variant since 2004. Currently, there are conflicting reports regarding its effect on the choroid, which supplies outer retina with oxygen and other nutrients. We synthesize available information of anti-VEGF on choroidal thickness (CT) in treatment-naïve typical neovascular AMD patients during the initial 12-week loading phase. We found 43 studies involving 1901 eyes from 1878 patients were included. Meta-analysis of 35 studies reporting CT at baseline and after 12 weeks suggested a significant decrease in CT with anti-VEGF treatment. A greater mean change with aflibercept compared to ranibizumab was found in subgroup analyses of sub-foveal CT in types 1 and 2 macular neovascularization. The long-term consequences of reduced CT in neovascular AMD remain unclear and require further targeted studies., Competing Interests: Declaration of Competing Interest None, (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the effects of faricimab, a bispecific antibody targeting VEGF and Ang-2 (thus increasing Tie-2 activity), in patients with CSC based on a recent genetic study that implicated Tie-2 signaling in CSC pathophysiology., Design: A retrospective interventional multicenter case series., Methods: We included patients with chronic CSC (persistent or recurrent SRF for ≥6 months) who received at least one faricimab 6 mg injection between January 1 2022, and April 1 2024,. Study sites included Massachusetts Eye and Ear and University of California San Francisco. Patients with evidence of a choroidal neovascular membrane on color photos, optical coherence tomography (OCT) and/or fluorescein angiography were excluded. 16 eyes (15 patients) met the inclusion criteria. The median central macular thickness at each visit from 52 weeks before to 52 weeks after the first faricimab injection was calculated using automated Heidelberg Spectralis ETDRS subfield measurements., Results: Prior to treatment with faricimab, CSC had been diagnosed a median of 4.1 years (range 0.9-8) earlier and SRF (and intraretinal fluid [IRF] in a subset) had been continuously present for a median of 30 weeks (range 9-257). Decreases in macular thickness were observed in 14/16 eyes after the first faricimab injection and in 14/16 eyes in the full follow-up period compared with prior, 10 of which experienced complete resolution of SRF following the start of the first series of injections at a median of 4 weeks (range 2-25). One eye worsened after the second injection. The median improvement in macular thickness was 40 μm [range -3 to 89.5] (P = .0007). Upon review of OCT images, reductions in macular thickness were consistent with reductions in SRF and/or IRF. Visual acuity improved by 2 lines or more in 6/16 eyes., Conclusions: In a retrospective case series of patients with chronic CSC and longstanding SRF, we observed improvement in macular thickness after intravitreal faricimab. While the small number of patients and variable natural history of CSC preclude definitive conclusions, a randomized controlled trial seems warranted., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Topic: This systematic review and meta-analysis investigates the efficacy and safety of anti-VEGF injections compared with surgical intervention in improving visual acuity (VA) and reducing complications for patients with submacular hemorrhage (SMH) due to neovascular age-related macular degeneration (AMD)., Clinical Relevance: Determining the optimal intervention for SMH in AMD is crucial for patient care., Methods: We included studies on anti-VEGF injections or surgical interventions for SMH in AMD from 7 databases, searched up to May 2024. Data extraction and quality assessment were done by 2 independent reviewers. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Meta-analysis employed random-effects models. Primary outcomes were pooled mean logarithm of the minimum angle of resolution VA difference (initial examination minus last follow-up VA) and adverse events rates., Results: A total of 43 observational studies were included: 21 (960 eyes) on anti-VEGF and 22 (455 eyes) on surgery. Comparisons were made across separate studies due to lack of head-to-head studies. Meta-analysis included 11 anti-VEGF studies (444 eyes) and 12 surgical studies (195 eyes) for VA outcomes. The mean difference in VA was -0.16 (95% confidence interval (CI), -0.24 to -0.08) for anti-VEGF and -0.36 (95% CI, -0.68 to -0.04) for surgery, with no significant difference between groups (chi-square = 1.70, df = 1, P = 0.19). Heterogeneity was high in surgical studies (I 2  = 96.2%, τ 2  = 0.23, P < 0.01) and negligible in anti-VEGF studies (I 2  = 7%, τ 2  = 0.003, P = 0.38). The GRADE certainty was moderate for anti-VEGF and low for surgery. Anti-VEGF had lower rates of cataract (0% vs. 4.6%), proliferative vitreoretinopathy (0.1% vs. 2.0%), and retinal detachment (0.1% vs. 10.6%), but similar rates of recurrent hemorrhage (5.4% vs. 5.3%). Complications were summarized descriptively due to zero-cell problem., Conclusion: Both anti-VEGF and surgery treat SMH in AMD with similar VA outcomes but different safety profiles. Anti-VEGF is preferred for less severe hemorrhage, whereas surgery is suited for extensive hemorrhage. Despite uncertain comparative VA outcomes, treatment should be guided by clinical judgment and patient factors., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Intravitreal (IVT) injection is an uncommon route of parenteral administration for therapeutic medications, but one of the most important for the treatment of ocular diseases, especially those related to macular degeneration. Nonetheless, there are currently no regulatory guidelines that specifically address how to establish a permitted daily exposure (PDE) for impurities and residual process reagents in IVT pharmaceutical drug products given the unique vulnerability of ocular tissues. The establishment of PDEs for IVT administration is complicated by the limited understanding of metabolism and clearance of small molecular weight chemicals from the human vitreous humor (VH), a problem compounded by the limited IVT-specific toxicological data. In this paper, we describe a feasible and comprehensive methodology for deriving PDE limits for impurities and residual process reagents from IVT drug products, as exemplified by five case studies, including inorganic elements, formic acid, polyethylene glycols, acetic acid, and caprolactam. The five case studies were selected to cover compounds with a wide range of impurity sources and toxicological data availability. The proposed framework considers both local ocular and systemic toxicity endpoints and advances the goal of a harmonized, science-based approach for deriving IVT PDE limits., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: To compare the incidence, type, interval for reactivation, and structural outcomes in infants with aggressive retinopathy of prematurity (A-ROP) treated with ranibizumab or bevacizumab., Method: It is a single-center, retrospective, consecutive, case series. We included infants with A-ROP which were initially treated with either intravitreal ranibizumab (IVR, 0.25 mg) or intravitreal bevacizumab (IVB, 0.625 mg) between January 2017 and December 2023. The infants were followed up for reactivation. The demographic and clinical data were collected. The time, zone, type of reactivation, its treatment, type of final structural outcome, and factors associated with reactivation were analyzed., Results: One hundred eight among the 322 infants with A-ROP were included in the study. Fifty-five received IVR, while 53 received IVB. Infants treated with IVR had higher incidence of reactivation (92.7% vs 52.8%, P < 0.001) at an earlier interval than IVB (7.7 weeks vs 12.8 weeks, P < 0.001). Infants treated with IVR had approximately 3.3 times higher possibility of reactivation than those treated with IVB. Three infants (5.9%) in the IVR group and five (9.4%) in the IVB group attained complete vascularization of the retina ( P = 0.72). More infants treated with IVB had regression with a persistent avascular retina (PAR) than IVR (52.8% vs 15.7%, P < 0.001). Infants in the IVB group had 10 times higher possibility of regression with PAR., Conclusion: Infants of A-ROP treated with IVR have a higher incidence and earlier reactivation, while those treated with IVB have less incidence and delayed reactivation, albeit with a higher possibility of regression with a PAR., (Copyright © 2024 Indian Journal of Ophthalmology.)

Purpose: To report the effect of anti-vascular endothelial growth factor inhibitor on fovea-involving cystoid macular edema in a patient with Birdshot chorioretinopathy., Methods: A 42-year-old male patient presented to our hospital with bilateral posterior uveitis with retinal vasculitis, cystoid macular edema, and optic disk edema. He was diagnosed with birdshot chorioretinopathy based on clinical appearance and tissue type HLA-A29., Results: The patient underwent vitrectomy in the right eye without any change in visual acuity. Retinal leakage was reduced by oral prednisolone, which could not be tapered below 50 mg per day without relapse. Oral prednisolone, topical dexamethasone, and subtenon Kenalog were associated with intraocular pressure rise in both eyes. Hence, his uveitis responded to steroids, but there was no detectable effect of any steroid-sparing immunomodulatory drugs. The patient had been on oral prednisolone 50 mg for five years when it was decided to attempt intravitreal vascular endothelial growth factor inhibitor injection therapy. The anti-vascular endothelial growth factor therapy diminished cystoid macular edema in the fovea and improved the visual acuity., Conclusion: Here, we report for the first time the long-term outcomes of anti-vascular endothelial growth factor injections on fovea-involving cystoid macular edema in Birdshot chorioretinopathy to keep steroid at the minimal possible doses and preserve a satisfying visual acuity level.

Introduction: New anti-vascular endothelial growth factor (VEGF) treatments are emerging for the treatment of diabetic macular edema (DME)/neovascular age-related macular degeneration (nAMD). This study aimed to explore the treatment attributes patients find important when deciding on treatment options., Methods: This noninterventional survey study assessed treatment preferences through a discrete choice experiment (DCE) among patients with DME/nAMD in the USA, Canada, France, Italy, Spain, and the UK. The DCE design was informed by a targeted literature review and qualitative interview research and included five treatment attributes: mode of administration, frequency of examinations, frequency of injections or refills, likely change in visual acuity, and eye-related side effects. Conditional logit models were used to analyze the choice data., Results: Overall, 537 patients completed the DCE (DME, n = 173; nAMD, n = 364). Patients reported preferring "injection" over "implant surgery and refills" and better visual outcomes over "stabilization," which were also the most important attributes driving preference (35.1% and 31.5%, respectively). They also showed a preference for less-frequent treatment and examinations and for "mild-moderate, frequent" over "severe, rare" side effects. These findings were generally consistent across the two conditions, although significant differences were found depending on anti-VEGF treatment duration (nAMD, DME) and number of reported barriers (nAMD)., Conclusion: Patient preferences for treatment are driven by several factors. Considering these preferences is essential when designing/introducing new therapies. Individual treatment preferences should be identified and given key consideration when helping patients select from an expanding array of treatment options., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Purpose: To evaluate the outcome and ocular adverse events of bedside bilateral sequential intravitreal anti-vascular endothelial growth factor injections for retinopathy of prematurity (ROP) (BBSIR)., Methods: This retrospective interventional study included infants who received BBSIR with a follow-up of at least 1 month. Clinical history, intravitreal injection details, indications, intraoperative and postoperative ocular adverse events, and outcomes were analyzed., Results: The study cohort included 192 babies (384 eyes) spread over 9 years. The mean gestational age was 30.2 ± 2.6 weeks (28.8-34.1), and the birth weight was 1098.11 ± 271.65 g (650-2000). The indications for BBSIR were as follows: 73.4% (n = 141 infants) were too sick to transfer to an ophthalmic unit, 10.9% (n = 21 infants) due to the parents' inconvenience of traveling to the ophthalmic center, and 15. 6% (n = 30 infants) due to both reasons. The injections were given by an ROP specialist/ROP-trained ophthalmologist after due parental consent, considering each eye as a fresh eye with separate scrubbing and draping. Light from the head-worn indirect ophthalmoscope served as the source of illumination. The retinopathy was regressing/regressed in 92.4% of babies until the last follow-up. The major ocular complication was cataract in 2 eyes (0.5%). There was no incidence of endophthalmitis till last follow-up (median 5.7 months)., Conclusions: As per this study, BBSIR was observed to be effective and safe if given by those fully trained in the management of ROP. Though the rate of complications like cataract is small, they can pose management challenges and impact vision in a growing child., (Copyright © 2024 Indian Journal of Ophthalmology.)

This study aimed to evaluate the changes in cytokine levels in the aqueous humor and factors of treatment resistance following intravitreal faricimab injection in treatment-naïve patients with neovascular age-related macular degeneration. A total of 32 eyes were analyzed before and after a single faricimab injection. Although the best-corrected visual acuity (BCVA) showed no significant improvement, the mean central retinal thickness decreased significantly by 73.7% (P < 0.01), and more than 90% of the eyes showed improvement in exudative changes 1 month after faricimab injection. Moreover, the aqueous humor concentrations of vascular endothelial growth factor (VEGF)-A, angiopoietin (Ang)-2, and placental growth factor considerably decreased 1 month after faricimab injection. Multivariate analyses adjusted for age, sex, BCVA, central choroidal thickness, and aqueous humor cytokines revealed that higher Ang-2 levels in the aqueous humor at baseline were associated with better treatment response to faricimab injection. These findings suggest that the dual inhibition of VEGF-A and Ang-2 by faricimab is effective in reducing exudative changes and that Ang-2 may serve as a potential biomarker for predicting faricimab treatment response., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. ., (© 2024. The Author(s).)

Background: Intravitreal anti-vascular endothelial growth factor (VEGF) treatment for diabetic macular oedema (DME) may begin with several initial monthly doses. Characteristics, treatment patterns and outcomes were compared for eyes with DME that did and did not receive such initial doses., Methods: This was a retrospective database study using American Academy of Ophthalmology Intelligent Research in Sight ® Registry data (01/01/15-31/12/20; index period). Eligible adults had documented DME within 2 months of first anti-VEGF treatment (index date), data available for 12 months beforehand, and ≥ 1 visual acuity (VA) recording ≤ 60 days before index date. Eyes must have received intravitreal anti-VEGF injections during the index period, but none in the prior 12 months. Characteristics and outcomes for eyes with initial doses (three injections within 100 days of index date) were compared with those without. Multivariate Cox Proportional Hazards modelling estimated predictors for treatment discontinuation, re-initiation, or switch; Generalized Estimating Equations-adjusted modelling estimated characteristics associated with receiving initial doses. Demographics and characteristics were summarised. Injection frequency and number, and VA were determined annually for ≤ 6 years. Discontinuations, reinitiations and switches were compared., Results: Included were 217,696 eyes (n = 77,769 initial; n = 139,927 non-initial) from 166,868 patients. Mean (SD) baseline VA was numerically higher for eyes with versus without initial doses (63.0 [18.1] vs. 62.5 [19.8] letters); this remained during follow-up. Based on modelling results, Eyes with initial doses received more injections (mean [standard deviation (SD)] 11.6 [8.9] vs. 6.1 [6.8] injections) more frequently (interval 7.6 [2.8] vs. 12.6 [7.7] weeks) than eyes without. These differences occurred across follow-up years. Discontinuation (45.7% vs. 63.8%), re-initiation (17.2% vs. 25.0%), and switch (24.5% vs. 31.5%) were less common with initial doses. Asian, Black, and patients of other/unknown race were less likely (P < 0.01) to receive initial doses than White patients, as were Medicare/Medicaid-insured patients versus commercially insured patients (P < 0.01)., Conclusions: Various sociodemographic factors associate with initial anti-VEGF doses, including race, ethnicity and insurance. Although eyes with frequent initial doses maintained higher VA than those without, they also receive more injections over time. Further research may elucidate the impact of frequent initial doses versus total injection number on DME outcomes., Competing Interests: Declarations. Ethics approval and consent to participate: No human participants were included in this study. This study adheres to the Declaration of Helsinki. The study was reviewed by WCG Institutional Review Board (IRB) (Puyallup, WA) and was considered exempt from ethical approval due to using anonymized, de-identified data. Furthermore, WCG IRB waived the need for patient consent as Veran Health certified the study was conducted on anonymized, deidentified data for research purposes. Consent for publication: Not applicable. Competing interests: AL and MH: Employee salary; stock or stock options – Verana Health. BLK: No conflicts of interest. DT, EK, and VG: Employee salary; Stock – Genentech, Inc. RPS: Personal fees – Genentech/Roche, Alcon, Novartis/Gyroscope, Apellis, Zeiss, Bausch + Lomb, Regeneron Pharmaceuticals, Inc. TL: Grants/Contracts – Astellas; Consulting fees – Alcon, Aptitude Medical, Astellas, Boehringer Ingelheim, Iridex, Nanoscope, Regeneron, Roche/Genentech, Verana Health, Virtual Field., (© 2024. The Author(s).)

Purpose: To evaluate early response of retinal sensitivity (RS) and retinal morphology in diabetic macular edema (DME) patients after intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment., Methods: Sixteen eyes of 12 DME patients were included in this study conducted prospectively. All eyes underwent functional and morphologic examination of the macular area using microperimetry and optical coherence tomography (OCT) before and after intravitreal anti-VEGF injection. To determine significant differences between the values, paired t test was used. A correlation between CMT and RS was made using Spearman's test., Results: Patients were evaluated at baseline, one week and one month after injection. The central macular thickness (CMT) decreased significantly from 449.33 ± 100.79 μm to 427.94 ± 85.76 μm to 357.93 ± 75.92 μm. The RS improved significantly from 7.94 ± 6.43 dB to 11.09 ± 7.42 dB at one week and to 14.22 ± 7.66 dB at one month after treatment. The CMT was significant negatively correlated to RS (r=-0.259, p = < 0.001), with decay of 0.025 dB for every 1 μm increase of CMT., Conclusions: Retinal thickening due to DME can be adequately quantified using OCT, while microperimetry can offer information about retinal sensitivity in the exact location. Therefore, microperimetry can be a useful tool in predicting the functional outcome and determining the efficacy of anti-VEGF treatment for DME patients., Competing Interests: Declarations. Ethics approval and consent to participate: No names, personal identification numbers, home addresses, contact information, photographs, or any other data that could be traced back to individual patients were collected. Further, no tissue specimens were analyzed in the project. Ethics approval and consent to participate that this study was approved by “Komite Etik Pusat Mata Nasional Rumah Sakit Cicendo” ethics committee. The requirement for informed consent was waived by “Komite Etik Pusat Mata Nasional Rumah Sakit Mata Cicendo” considering that the study used no sensitive patient information; did not entail any treatment, other interventions, tests, examinations, or interviews; did not affect follow-up; did not expose patients to any risk of physical, psychological or other harm; and used no biological samples. The study adhered to the tenets of the Declaration of Helsinki. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Purpose: To determine if demographic factors and calculated areas of nonperfusion (NP) and neovascularization (NV) on ultra-widefield (UWF) fluorescein angiography (FA) in the eyes of patients with diabetes are associated with treatment with intravitreal injections (IVIs), panretinal photocoagulation (PRP), and diabetic retinopathy (DR) progression., Patients and Methods: This retrospective, cross-sectional study included 363 patients (651 eyes) treated at the University of Michigan Kellogg Eye Center between January 2009 and May 2018. Eligible participants were 18 years or older diagnosed with diabetes who received UWF FA. Patients with previous PRP or poor-quality images were excluded. Main outcome measures included comparison analyses of measured surface areas in millimeters squared (mm 2 ) of total and regional retinal nonperfusion and neovascularization, number of IVIs and PRP treatments, and DR progression., Results: Our cohort received 3,041 IVIs and 878 PRP treatments with a mean follow-up of 915 days (SD ±714). IVIs were positively associated with posterior NP (difference, 1.15 mm 2 ; 0.43-1.86; P= 0.0017). PRP treatments were positively associated with total NP (difference, 27.24 mm 2 ; 14.68-39.79; P <0.001) and total NV (difference, 1.75 mm 2 ; 0.84-2.65; P <0.001), as well as regional areas. While progression was not associated with NP/NV area, it was positively associated with a pre-existing diagnosis of type 2 as compared to type 1 diabetes (147% increase; 7-373% increase; p =0.03)., Conclusion: Areas of NP and NV on UWF FA demonstrated associations with PRP and IVIs in DR patients., Competing Interests: Yannis Paulus reports consulting fees from Iridex, Inc., grants from Alcon Research Institute Young Investigator Grant, grants from Research to Prevent Blindness, during the conduct of the study and is a Founder with equity from Photosonox, LLC outside the submitted work. The remaining authors report no conflicts of interests or competing interests., (© 2024 Iyengar et al.)

Aims: To assess the feasibility of a study protocol for a randomised controlled trial of zoledronic acid (ZA) as adjuvant therapy for neovascular age-related macular degeneration (nAMD)., Methods: In this 1-year, randomised, double-blinded, placebo-controlled pilot study, nAMD patients were allocated 1:1 to receive intravenous ZA 5 mg or placebo at baseline and after 6 months in addition to intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy following a treat-and-extend regimen. Bevacizumab was the first-line anti-VEGF drug, but eyes with refractory nAMD were switched to aflibercept. The primary outcome was mean change in best-corrected visual acuity (BCVA)., Results: 40 participants enrolled in the study, with 20 allocated to each treatment group. 38 participants received both study infusions, and all participants completed the final assessment. Mean (SD) change in BCVA was 7.5 (9.5) letters in the ZA group and -0.5 (11.5) letters in the control group; the between-group difference was 8.0 letters (95% CI: 1.5 to 15.0 letters). There were no between-group differences in mean change in central retinal thickness, refractory nAMD proportion or mean number of injections., Conclusion: It is feasible to conduct a randomised controlled trial of ZA as adjuvant therapy for nAMD in terms of recruitment and adherence to the pilot study protocol. We found a possible visual benefit of ZA that is worth further investigation. To clarify the relationship between ZA and the need for intravitreal injections, we recommend amending the protocol by omitting switching of the anti-VEGF drug. Due to the limited sample size of the pilot study, the estimates of treatment effect are not meant to be confirmatory and should be interpreted with caution., Trial Registration Number: 2019-001492-37 (EudraCT), 04304755 (NCT)., Competing Interests: Competing interests: YSH has nothing to disclose. EFE has received lecture fees and been member of Amgen, Ascendis, Gedeon Richter, Pharmamedico, Takeda, and UCB advisory boards. MWF has nothing to disclose. MCM has received lecture fees from Bayer and Roche and has been member of Allergan, Apellis, Bayer, Novartis, Roche, and SJJ Solutions advisory boards, and is co-owner of a patent for a needle for intravitreal injection. ØKJ has received lecture fees from Allergan and Bayer, has been member of Allergan, Bayer, Roche, and SJJ Solutions advisory boards, has received travel support and royalties from SJJ Solutions, and is co-owner of a patent for a needle for intravitreal injection., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Diabetic vitrectomy is a highly intricate surgical procedure performed during the advanced stages of diabetic retinopathy (DR). It is used to treat conditions such as tractional or combined retinal detachment, vitreous hemorrhage, and subhyaloid hemorrhage, which are all severe manifestations of proliferative DR. The results of the surgery are uncertain and variable. Vitreoretinal surgery has made significant progress since the early stages of vitrectomy. In the past ten years, advancements in intravitreal pharmacotherapy have emerged, offering new possibilities to improve the surgical results for our patients. Within the realm of medical terminology, an "adjunct" refers to a pharmaceutical or substance employed to aid or expedite the primary therapeutic intervention for a particular ailment. Their introduction has broadened the range of therapeutic choices that are accessible prior to, during, and following surgical procedures. This review article will specifically analyze the pharmacological adjuncts used in diabetic vitrectomy surgery, with a focus on their role in facilitating or aiding specific steps of the procedure. The implementation of this system of categorization offers benefits to the surgeon by allowing them to foresee potential difficulties that may occur during the surgical procedure and to choose the appropriate pharmacological agent to effectively tackle these challenges, thus enhancing surgical success rates., Competing Interests: Conflict-of-interest statement: None of the authors have anything to declare., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Age-related macular degeneration (AMD) stands as the primary cause of visual impairment and blindness among the elderly population. Patients over 90 years comprise a unique demographic that may necessitate particular attention. The aim of this study was to examine the clinical characteristics and treatment outcomes in patients aged 90 years or older diagnosed with neovascular age-related macular degeneration (nAMD)., Methods: The medical records of treatment-naive patients aged ≥ 90 years diagnosed with nAMD have been retrospectively reviewed in our clinic. The complete ophthalmic examination findings of the patients, along with optical coherence tomography and fundus fluorescein angiography records, as well as their adherence to treatment, and reasons for treatment discontinuation were noted. Clinical data following intravitreal injection loading dose and during the 1st and 2nd years of treatment were evaluated., Results: The average age of the 45 participants (25 females, 20 males) included in the study was 93.55 ± 5.2 years (range; 90-101). The mean best-corrected visual acuity at diagnosis, at the 4th month of treatment, and during the 1st and 2nd years were LogMAR 0.8, 0.5, 0.7 and 1.0, respectively. The most common reasons for missing appointments and completely discontinuing treatment were death and inability to attend appointments due to additional comorbidities., Conclusion: In the very elderly patient group, nAMD can lead to severe damage in the macula, and a decrease in visual acuity despite treatment is not uncommon. Close monitoring and support for treatment adherence are necessary for this group of patients., Competing Interests: Declarations. Ethics approval and consent to participate: All subjects were informed about the disease and treatment protocols, and informed consent for intravitreal injections was obtained. This study followed the tenets of the Declaration of Helsinki and the protocol was approved by the Recep Tayyip Erdogan University Ethics Committee. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Introduction: Intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents are a primary management option for retinal diseases. Acute elevation of intraocular pressure (IOP) is a complication associated with these injections that should be considered. This study investigated and compared the prophylactic effects of fixed combination anti-glaucoma medication on IOP spikes following intravitreal anti-VEGF injections., Methods: This randomized double-blind clinical trial included one eye of each participant indicated for treatment with intravitreal injection of anti-VEGF agents (bevacizumab, aflibercept, and ranibizumab) and randomly allocated to one of the three prophylactic anti-glaucoma medications, with each drug further divided into one- and two-drop regimens before intravitreal injection. Participants with allergies or contraindications to medications were excluded from the pretreatment groups and were invited to participate in the control group., Results: The study involved 308 participants: 89 in the dorzolamide/timolol group, 86 in the brimonidine/timolol group, 101 in the brinzolamide/brimonidine group, and 32 in the control group. Baseline characteristics and IOP were comparable across all groups. In the prophylactic premedication groups, mean IOP at 30 min were within 21 mmHg and returned to their baseline at 1 h. Mean IOP measurements between baseline and 30 min in the brimonidine/timolol two-drop regimen were not significantly different: 13.72 ± 4.63 vs 15.11 ± 4.39 mmHg, p = 0.096. In the control group, IOP significantly increased from baseline at 30 min and 1 h post-injection: 14.31 ± 4.10, 22.15 ± 8.64, and 18.36 ± 7.52 mmHg, respectively, p < 0.001., Conclusion: Topical fixed combination anti-glaucoma medication used as a prophylactic treatment before intravitreal anti-VEGF injections significantly prevented IOP spikes post-injection, with a comparable effect among three medications. Prophylactic treatment of IOP spikes should be considered as standard care to prevent further damage in patients with compromised retinal vascular and optic nerve perfusion., Trial Registration: TCTR20241005001, retrospectively registered., Competing Interests: Declarations. Conflict of Interest: Piriya Soomsawasdi, Kulawan Rojananuangnit, Eakkachai Arayangkoon, Ratchada Chantiwas, Sureeporn Pengrungreungwong, Nontakorn Preawsampran, Natnaree Tinpowong, Rujira Samakhararaksakul, Kanokwan Katkingkaew, Natthapuch Seekhum, and Wanwisa Sathim declare that they have no competing interests. Ethical Approval: This randomized double-blind clinical trial was approved by the Mettapracharak (Wat Rai Khing) Research Ethics Committee in accordance with the International Conference on Harmonization Good Clinical Practice (ICH-GCP) COA No 015/2563. The study was performed in accordance with the Helsinki Declaration of 1964. All participants provided informed consent to participate in the study. All privacy data including hospital number, name, and date of birth were masked and kept confidential., (© 2024. The Author(s).)

Background/aims: This study aimed to investigate the clinical characteristics and treatment outcomes of patients with active central serous chorioretinopathy (CSC) and foveal atrophy., Methods: Patients diagnosed with active idiopathic CSC using multimodal imaging and followed up for at least 6 months were included. They were divided into two groups (foveal atrophy group vs foveal non-atrophy group) according to a cut-off central foveal thickness of 120 µm on baseline optical coherence tomography (OCT). Baseline characteristics, angiographic and tomographic features and treatment outcomes were compared between the two groups., Results: Of the 463 patients, 92 eyes of 92 patients (19.9%) were in the foveal atrophy group and 371 eyes of 371 patients (80.1%) were in the foveal non-atrophy group. The baseline subretinal fluid (SRF) height was 111.3±76.8 µm in the foveal atrophy group and 205.0±104.4 µm in the foveal non-atrophy group on OCT images (p<0.001). Complete resolution of SRF after treatment was noted in 60.4% and 93.5% of patients in the foveal atrophy and foveal non-atrophy groups at the final visit, respectively (p<0.001). The foveal atrophy group showed worse visual acuity at baseline (logarithm of the minimum angle of resolution, 0.43±0.33 vs 0.13±0.18, p<0.001) and final visit (0.41±0.32 vs 0.05±0.15, p=0.035)., Conclusions: CSC with foveal atrophy was associated with a shallow SRF height, low treatment efficacy and poor vision before and after treatment. We suggest that early active treatment should be considered for eyes with CSC accompanied by a persistent shallow SRF and foveal atrophy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Background/aims: To determine the suitability of functional MRI (fMRI) as an objective measure of macular function following therapeutic intervention; conventional psychophysical measures rely heavily on patient compliance., Methods: Twenty patients with neovascular age-related macular degeneration (nAMD) were studied with high-resolution fMRI, visual acuity, reading accuracy and speed, contrast sensitivity (CS) and microperimetry (MP) before and after 3 monthly intravitreal injections of ranibizumab. Population-receptive field retinotopic maps calculated from fMRI data were compared with psychophysical measures and optical coherence tomography., Results: Best-corrected visual acuity (BCVA) responders (≥5 letters) showed an increase of 29.5% in activated brain area, while non-responders showed a decrease of 0.8%. Radial histograms over eccentricity allowed quantification of the absolute number of significant voxels and thus differences before and after treatment. Responders showed increases in foveal (α<0.5°) activation, while non-responders did not. Absence of intraretinal fluid and preservation of outer retinal layers was associated with higher numbers of active V1 voxels and better BCVA. Higher voxel numbers were associated with improved reading performance and, less marked, with BCVA, CS and MP., Conclusion: The data show that retinotopic mapping using fMRI can successfully be applied objectively to evaluate the therapeutic response in nAMD patients treated with anti-vascular endothelial growth factor therapy. This demonstrates the ability of retinotopic mapping to provide an objective assessment of functional recovery at a cortical level; the technique can therefore be applied, in other degenerative macular diseases, to the assessment of potential therapeutic interventions such as gene therapy or cell replacement therapy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)