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Abstract Background  Most uveal melanomas are currently treated by eye-preserving radiotherapies. However, for melanomas of the largest size or with initial complications, enucleation remains the reference treatment. Enucleation is called primary when it is proposed as the only local treatment option for a melanoma. There is very little literature on the use of primary enucleation after the introduction of conservative treatments. Our main goal was to evaluate the survival of melanoma patients treated by primary enucleation since the introduction of proton-beam therapy in France in 1991. Methods  All melanoma patients undergoing primary enucleation in our department between 1991 and 2002 were included in this retrospective study. The 5-year melanoma-specific survival rate was calculated using the Kaplan–Meier method. The multivariate prognostic analysis was performed using the Cox proportional hazards model. Results  Forty patients, representing 8% of all patients with choroidal uveal melanoma diagnosed and followed up in our department during an 11-year period, were included in the study. No patient was lost to follow-up. The 5-year melanoma-specific survival rate was 31.45% (SE: 7.8) after primary enucleation. Significant prognosis factors in the multivariate analysis were: tumor thickness > 12 mm (p = 0.03), anterior margin of the tumor involving the iris (p = 0.018), and presence of epithelioid cells (p = 0.02). Conclusions  The very low survival rate reported reflects the evolution of primary enucleation, which is currently indicated only for melanomas with the worst prognosis. The knowledge of current post-enucleation survival rates represents an essential achievement for both correct assessment of conservative therapies and patient counseling. [ABSTRACT FROM AUTHOR]

Introduction: Neovascular age-related macular degeneration is a global public-health concern, associated with a considerable burden to individuals, healthcare systems, and society. The objective of this study was to understand different perspectives on the challenges associated with the clinical management of neovascular age-related macular degeneration, which could elucidate measures to comprehensively improve clinical care and outcomes., Methods: A survey was carried out of patients with neovascular age-related macular degeneration, their providers, and clinic staff in 77 clinics across 24 countries on six continents, from a diverse range of healthcare systems, settings, and reimbursement models. Surveys comprised a series of single/multiple-response questions completed anonymously. Data gathered included patient personal characteristics, appointment attendance challenges, treatment experiences, and opportunities to improve support. Provider and clinic staff surveys asked similar questions about their perspectives; clinic characteristics were also captured., Results: There were 6425 responses; 4558 patients with neovascular age-related macular degeneration, 659 providers, and 1208 clinic staff. Challenges identified included concern about patient burden to family/friends, high frequency of treatment, difficulties in traveling to appointments, long waiting times, and insufficient comprehension of neovascular age-related macular degeneration. Participants identified logistical (improved financial assistance with treatment and out-of-pocket costs, and appointment reminders), operational (addressing clinic set up to reduce waiting times and improving the amount of time providers spend with patients), and educational (improving quality and provision of patient information and expectation-setting) opportunities to improve care., Conclusions: The wealth of data generated by this global survey highlights the breadth of challenges associated with clinical management of patients with neovascular age-related macular degeneration. Addressing the opportunities raised could improve patient adherence to treatment and potentially outcomes, reduce appointment burden, and increase clinic capacity., Competing Interests: Declarations. Conflict of Interest: Anat Loewenstein: Consultant: 4DMT, AbbVie, Alkeus, Annexon, Apellis, Astellas, Bayer Health Care, Beyeonics, Eyepoint, Johnson & Johnson, NotalVision, Novartis, Ocular Therapeutics, Oculis, Ocuphire Pharma, Ocuterra, Opthea, Oxurion, Roche, Syneos; Michelle Sylvanowicz: Employee: Bayer; Winfried M. Amoaku: Advisory board membership: AbbVie, Alcon, Alimera, Allergan, Apellis, Bayer, Bausch + Lomb, Bioeq, Novartis, Pfizer; Speaker fees: Alimera, Allergan, Bayer, Novartis, Pfizer; Support for travel: Alimera, Allergan, Bayer, Novartis, Pfizer; Research sponsorship and funding: Allergan, Bayer, Boehringer Ingelheim, CenterVue, Gyroscope, Novartis, Optos; Tariq Aslam: Tariq Aslam is an Editor in Chief of Ophthalmology and Therapy, and was not involved in the selection of peer reviewers for the manuscript nor any subsequent editorial decisions. Consultant: Novartis, Bayer, Laboratoires, Théa Pharmaceuticals, Bausch & Lomb, Oraya; Chui Ming Gemmy Cheung: Financial support (to institution): Allergan, Bayer, Boehringer Ingelheim, Novartis, Roche, Topcon, Zeiss; Stock: Avirmax; Bora Eldem: Consultant: Allergan, Bayer, Novartis, Roche; Robert P. Finger: Research grant: CentreVue, Heidelberg Engineering, Novartis, Zeiss; Consultant: Alimera, Allergan, Bayer, Ellex, Inositec, Novartis, Opthea, Roche/Genentech, Santhera; Support for travel: Novartis; Richard P. Gale: Consultant/advisory boards: Allergan, Alimera, Bayer, Novartis, Santen; Educational travel grants: Allergan, Bayer, Heidelberg, Novartis; Research grants: Allergan, Bayer, Novartis, Roche; Laurent Kodjikian: Consultant: AbbVie, Alcon, Allergan, Bayer, Krystal Biotech, Novartis, Regeneron, Théa; Adrian Koh: Consultant: Allergan, Bayer, Carl Zeiss, Heidelberg, Novartis, Topcon; Jean-François Korobelnik: Consultant: AbbVie, Apellis, Bayer, Eyepoint Pharma, Ocuphire, Roche, Thea, Carl Zeiss Meditec; Member of DSMB for Alexion, Novo Nordisk, Opthea; Xiaofeng Lin: Consultant: Bayer; Paul Mitchell: Consultant: Allergan, Bayer, Novartis; Steering Committee member: Bayer; Moira Murphy: Employee: Exploristics, Ltd.; Mali Okada: Non-financial support and personal fees: Bayer; Ian Pearce: Lecture fees: Allergan, Bayer, Heidelberg, Novartis; Consultant: Allergan, Alimera, Bayer, Novartis; Support for travel: Allergan, Bayer, Novartis; Francisco J. Rodriguez: Consultant: Bayer, Novartis, Roche; Speaker: Bayer, Novartis, Roche; Research funding: Novartis; Jude Stern: Employee: The International Agency for the Prevention of Blindness; S. James Talks: Advisory board member, speaker fees, and research support: Bayer, Novartis; research grants: Boehringer Ingelheim, Roche; Consultant: Bayer; David T. Wong: Grants/research support: Bayer, Novartis, Roche; Consultant: Alcon, Allergan, Bausch Health, Bayer, Novartis, Topcon, Zeiss; Equity: Arctic DX; Tien Yin Wong: Clinical trial grants: Allergan, Bayer, Boehringer Ingelheim, Genentech, Merck, Novartis, Oxurion (formerly ThromboGenics), Roche, Samsung Bioepis, NMRC Singapore, Novartis Singapore; Consulting fees/travel support/review fees: Allergan, Bayer, Boehringer Ingelheim, Genentech, Merck, Novartis, Oxurion (formerly ThromboGenics), Roche, Samsung Bioepis; Stock: EyRIS, Plano; Focke Ziemssen: Travel grants and personal fees: Allergan, Alimera, Bayer Healthcare, Biogen, Boehringer Ingelheim, Clearside, Novartis, Novo Nordisk, MSD Sharp & Dohme, Roche, Optos; Jane Barratt: Consultant: Bayer. Ethical Approval: The survey was designed and developed according to the Declaration of Helsinki and the World Health Organization’s International Ethical Guidelines for Biomedical Research. While the survey is a Primary Market Research Survey (which does not require ethics committee approval), individual institutions and countries assessed local requirements. Furthermore, informed consent was acquired, no personally identifiable information was collected, and treatment decisions were not informed by response to the survey., (© 2024. The Author(s).)

Introduction: In contrast with patients receiving therapy for retinal disease during clinical trials, those treated in routine clinical practice experience various challenges (including administrative, clinic, social, and patient-related factors) that can often result in high patient and clinic burden, and contribute to suboptimal visual outcomes. The objective of this study was to understand the challenges associated with clinical management of diabetic macular edema from the perspectives of patients, healthcare providers, and clinic staff, and identify opportunities to improve eye care for people with diabetes., Methods: We conducted a survey of patients with diabetic macular edema, providers, and clinic staff in 78 clinics across 24 countries on six continents, representing a diverse range of individuals, healthcare systems, settings, and reimbursement models. Surveys comprised a series of single- and multiple-response questions completed anonymously. Data gathered included patient personal characteristics, challenges with appointment attendance, treatment experiences, and opportunities to improve support. Provider and clinic staff surveys asked similar questions about their perspectives; and clinic characteristics were also captured., Results: Overall, 5681 surveys were gathered: 3752 from patients with diabetic macular edema, 680 from providers, and 1249 from clinic staff. Too many appointments, too short treatment intervals, difficulties in traveling to the clinic or arranging adequate support to travel, out-of-pocket costs, office/parking fees, and long waiting times were noted by all as contributing to increase the burden on the patient and caregiver. Patients generally desired more in-depth discussions with their provider, which would help with information exchange and better expectation-setting., Conclusions: The wealth of systematic data generated by this global survey highlights the breadth and scale of challenges associated with the clinical management of patients with diabetic macular edema. Addressing the opportunities for improvement raised by patients, providers, and clinic staff could increase patient adherence to treatment, reduce appointment burden, and improve clinic capacity., Competing Interests: Declarations. Conflict of Interest: Focke Ziemssen: Travel grants and personal fees: Allergan/AbbVie, Alimera, Bayer Healthcare, Biogen, Boehringer Ingelheim, Clearside, Janssen, Novartis, Novo Nordisk, Merck, Sharp & Dohme, Regeneron, Roche/Genentech, Sanofi, Sandoz, and Stada. Michelle Sylvanowicz: Employee: Bayer; Winfried M. Amoaku: Advisory board membership: AbbVie, Alcon, Alimera, Allergan, Apellis, Bayer, Bausch + Lomb, Bioeq, Novartis, and Pfizer; Speaker fees: Alimera, Allergan, Bayer, Novartis, and Pfizer; Support for travel: Alimera, Allergan, Bayer, Novartis, and Pfizer; Research sponsorship and funding: Allergan, Bayer, Boehringer Ingelheim, CenterVue, Gyroscope, Novartis, and Optos; Tariq Aslam: Tariq Aslam is an Editor in Chief of Ophthalmology and Therapy, and was not involved in the selection of peer reviewers for the manuscript nor any subsequent editorial decisions. Consultant: Bausch & Lomb, Bayer, Laboratoires Théa Pharmaceuticals, Novartis, Oraya, and Roche; Bora Eldem: Consultant: Allergan, Bayer, Novartis, and Roche; Robert P. Finger: Research grant: CentreVue, Heidelberg Engineering, Novartis, and Zeiss; Consultant: Alimera, Allergan, Bayer, Ellex, Inositec, Novartis, Opthea, Roche/Genentech, and Santhera; Support for travel: Novartis; Richard P. Gale: Consultant/advisory boards: Allergan, Alimera, Bayer, Novartis, and Santen; Educational travel grants: Allergan, Bayer, Heidelberg, and Novartis; Research grants: Allergan, Bayer, Novartis, and Roche; Laurent Kodjikian: Consultant: AbbVie, Alcon, Allergan, Bayer, Krystal Biotech, Novartis, Regeneron, and Théa; Jean-François Korobelnik: Consultant: AbbVie, Apellis, Bayer, Eyepoint Pharma, Ocuphire, Roche, Thea, Carl Zeiss Meditec; Member of DSMB for Alexion, Novo Nordisk, Opthea; Xiaofeng Lin: Consultant: Bayer; Anat Loewenstein: Consultant: 4DMT, AbbVie, Alkeus, Annexon, Apellis, Astellas, Bayer Health Care, Beyeonics, Eyepoint, Johnson & Johnson, NotalVision, Novartis, Ocular Therapeutics, Oculis, Ocuphire Pharma, Ocuterra, Opthea, Oxurion, Roche, Syneos; Paul Mitchell: Consultant: Allergan, Bayer, and Novartis; Steering Committee member: Bayer; Moira Murphy: Employee: Exploristics, Ltd.; David R. Owens: Consultant: Bayer; Nick Parker: Employee: The International Agency for the Prevention of Blindness; Ian Pearce: Lecture fees: Allergan, Bayer, Heidelberg Pharma, and Novartis; Consultant: Allergan, Alimera, Bayer, and Novartis, Support for travel: Allergan, Bayer, and Novartis; Francisco J. Rodríguez: Consultant: Bayer, Novartis, and Roche; Speaker: Bayer, Novartis, and Roche; Research funding: Novartis; Jude Stern: Employee: The International Agency for the Prevention of Blindness; S. James Talks: Advisory board member, speaker fees, and research support: Bayer and Novartis; Research grants: Boehringer Ingelheim and Roche; Consultant: Bayer; David T. Wong: Grants/research support: Bayer, Novartis, and Roche; Consultant: Alcon, Allergan, Apellis, Bausch Health, Bayer, Novartis, Roche, Topcon, and Zeiss; Equity: Arctic DX; Tien Yin Wong: Consulting fees/travel support/review fees: Aldropika Therapeutics, Bayer, Boehringer Ingelheim, Genentech, Iveric Bio, Novartis, Oxurion, Plano, Roche, Sanofi, Shanghai Henlius; Stock: EyRIS; Jane Barratt: Consultant: Bayer. Ethical Approval: The survey was developed according to guidelines from the Declaration of Helsinki and the World Health Organization’s International Ethical Guidelines for Biomedical Research. As a Primary Market Research Survey, ethics committee approvals are not required; however, local requirements were assessed by individual institutions and countries. Informed consent was acquired, no personally identifiable information was collected, and the survey did not inform treatment decisions., (© 2024. The Author(s).)

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.)

Background/objectives: The large number and heterogeneity of causes of uveitis make the etiological diagnosis a complex task. The clinician must consider all the information concerning the ophthalmological and extra-ophthalmological features of the patient. Diagnostic machine learning algorithms have been developed and provide a correct diagnosis in one-half to three-quarters of cases. However, they are not integrated into daily clinical practice. The aim is to determine whether machine learning models can predict the etiological diagnosis of uveitis from clinical information., Methods: This cohort study was performed on uveitis patients with unknown etiology at first consultation. One hundred nine variables, including demographic, ophthalmic, and clinical information, associated with complementary exams were analyzed. Twenty-five causes of uveitis were included. A neural network was developed to predict the etiological diagnosis of uveitis. The performance of the model was evaluated and compared to a gold standard: etiological diagnosis established by a consensus of two uveitis experts., Results: A total of 375 patients were included in this analysis. Findings showed that the neural network type (Multilayer perceptron) (NN-MLP) presented the best prediction of the etiological diagnosis of uveitis. The NN-MLP's most probable diagnosis matched the senior clinician diagnosis in 292 of 375 patients (77.8%, 95% CI: 77.4-78.0). It achieved 93% accuracy (95% CI: 92.8-93.1%) when considering the two most probable diagnoses. The NN-MLP performed well in diagnosing idiopathic uveitis (sensitivity of 81% and specificity of 82%). For more than three-quarters of etiologies, our NN-MLP demonstrated good diagnostic performance (sensitivity > 70% and specificity > 80%)., Conclusion: Study results suggest that developing models for accurately predicting the etiological diagnosis of uveitis with undetermined etiology based on clinical information is feasible. Such NN-MLP could be used for the etiological assessments of uveitis with unknown etiology., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Aims: To compare the safety and efficacy of methotrexate (MTX), mycophenolate mofetil (MMF) and azathioprine (AZA) in non-anterior sarcoidosis-associated uveitis., Methods: Retrospective study including non-anterior sarcoidosis-associated uveitis according to the revised International Workshop on Ocular Sarcoidosis criteria. The primary outcome was defined as the median time to relapse or occurrence of serious adverse events leading to treatment discontinuation., Results: 58 patients with non-anterior sarcoidosis-associated uveitis (MTX (n=33), MMF (n=16) and AZA (n=9)) were included. The time to treatment failure (ie, primary outcome) after adjustment for corticosteroids dose and the presence of vasculitis was significantly higher with MTX (median time of 34.5 months with MTX (IQR: 11.8 -not reached) vs 8.4 months (3.1-22.9) with MMF and 16.8 months (8.0-90.1) with AZA (p=0.020)). The risk of relapse at 12 months was more than twice lower in MTX as compared with MMF (p=0.046). Low visual acuity at the last visit was significantly lower with MTX (4% vs 9% in MMF vs 57% in AZA group (p=0.008)). Regarding all 75 lines of treatment (MTX (n=39), MMF (n=24) and AZA (n=12)), MTX was more effective than MMF and AZA to obtain treatment response at 3 months (OR 10.85; 95% CI 1.13 to 104.6; p=0.039). Significant corticosteroid-sparing effect at 12 months (p=0.035) was only observed under MTX. Serious adverse events were observed in 6/39 (15%), 5/24 (21%) and 2/12 (17%) with MTX, MMF and AZA, respectively., Conclusion: In non-anterior sarcoidosis-associated uveitis, MTX seems to be more efficient compared with AZA and MMF and with an acceptable safety profile., Competing Interests: Competing interests: Bahram Bodaghi: Alimera, Abbvie, Optos, Zeiss, Thea, Horus, Active biotech. Laurent Kodjikian: Alimera, Abbvie, Novartis, Bayer, Roche, Horus, Krys. Sara Touhami: Allergen, Novartis, Horus, Bayer pharma. Pascal Sève: Abbvie, Pfizer, Sanofi, Lilly, GSK, UCB Pharma., (© Author(s) (or their employer(s)) 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Ocular toxoplasmosis is the most common cause of posterior uveitis worldwide, with an estimated incidence of 8.4%. It follows infection by the ubiquitous parasite Toxoplasma gondii. The diagnosis is based on clinical examination looking for uveitis and most often retinochoroiditis. Microbiological confirmation is an element of positive diagnosis. The indications for treatment remain debated, whether for acute forms or recurrences., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Purpose: To assess the efficacy and safety of 0.19-mg fluocinolone acetonide (FAc) intravitreal implant (Iluvien) in treating chronic postoperative cystoid macular edema (PCME) after pars plana vitrectomy., Design: Retrospective multicentric case series in clinical settings., Subjects: Patients with chronic PCME who underwent vitrectomy in tertiary care centers in France., Methods: Review of charts and OCT scans., Main Outcome Measures: The primary end points were the best-corrected visual acuity (BCVA) and central retinal thickness (CRT). Secondary end points were the intraocular pressure (IOP); proportion of patients maintaining a BCVA ≥20/40; need for additional nonstudy treatment; differences between eyes that underwent a single and multiple surgeries; and OCT biomarkers of better BCVA., Results: Forty-nine eyes of 49 patients with a mean follow-up of 24.5 ± 3.87 months were included. The mean BCVA increased from 0.40 ± 0.26 logarithm of the minimum angle of resolution (logMAR) at baseline to 0.32 ± 0.24 logMAR at month 24 (P = 0.0035). The mean CRT decreased from 409 ± 139 μm at baseline to 340 ± 92 μm at month 24 (P = 0.0001). The mean IOP was 14.0 ± 4 mmHg at baseline and remained stable at 14.03 ± 4.1 mmHg at month 24 (P = 0.99). During the follow-up, the IOP exceeded 21 mmHg in 9 eyes, with one eye requiring cyclophotocoagulation. The BCVA was ≥20/40 in 47% of eyes (95% confidence interval [CI], 34%-61%) at baseline and in 58% of eyes at month 24 (95% CI, 41%-73%). At month 18, the likelihood of achieving a BCVA ≥20/40 was higher in eyes with intact external limiting membrane and ellipsoid zone. Additional dexamethasone (DEX) implant was injected in 14 eyes (28.6%). The treatment burden of 2.45 ± 1.35 DEX implant/y was decreased to 0.57 ± 0.60 DEX implant/y after FAc implantation (P = 0.001)., Conclusions: Fluocinolone acetonide implant improved the BCVA, reduced the CRT, and allowed reducing treatment burden in eyes with chronic PCME after vitrectomy. The safety profile was acceptable., 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.)

Despite its indolent evolution, vitreoretinal lymphoma (VRL) has a poor prognosis due to a major risk of relapse in the central nervous system (CNS) and may necessitate aggressive therapy. However, the use of high-dose chemotherapy with autologous stem cell transplantation (HCT-ASCT) is poorly documented. We retrospectively analysed from the French LOC network database the adult immunocompetent patients treated with HCT-ASCT for isolated VRL. Thirty-eight patients underwent consolidation with HCT-ASCT for isolated VRL between 2008 and 2019 after induction chemotherapy. Twenty patients had primary VRL, and 18 had an isolated VRL relapse of a primary CNS lymphoma. Three patients underwent HCT-ASCT in first-line treatment, 24 in second-line treatment, and 11 in subsequent lines. At HCT-ASCT, the median age was 61 years, and the median KPS was 90. Thirty-two patients (84%) received high-dose thiotepa-based HCT. One patient (3%) died from HCT-ASCT toxicity. Nineteen (50%) patients relapsed after HCT-ASCT, including 17 cases occurring in the brain. The median progression-free survival, brain-free survival and overall survival from HCT-ASCT were 96, 113 and 92 months, respectively. HCT-ASCT represents an effective therapeutic strategy for select VRL patients, with a tolerable safety profile. However, the risk of subsequent brain relapse remains significant., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Purpose: To compare refractive outcomes of the foldable intraocular lens sutureless scleral fixated sutureless (Carlevale® FIL-SSF) with the iris-claw lens (Artisan®)., Methods: This retrospective study included consecutive patients who underwent a FIL-SSF implantation or an iris-claw implantation between January 2020 and November 2022 in the ophthalmology departments of Hospices Civils de Lyon (France)., Results: A total of 271 eyes from 265 patients were included: 96 eyes in the FIL-SSF group and 175 eyes in the iris-claw group. At 6 months, the mean (SD) surgically induced astigmatism (SIA) was significantly lower in the FIL-SSF group with 0.3 (1.8) diopters against 0.8 (2.1) diopters in the iris-claw group (p = 0.01). The mean (SD) refractive error was also lower for the FIL-SSF group with 0.1 (1.2) diopters versus 0.5 (1.6) diopters in the iris-claw group (p < 0.001). The mean best corrected visual acuity at 6 months was not significantly different between FIL-SSF and iris-claw lens with 0.47 (0.58) logMAR and 0.39 (0.55) logMAR, respectively (p = 0.12). However, the mean (SD) operative time was longer for FIL-SSF implantation in comparison to iris-claw implantation (59.8 (21.1) minutes versus 41.9 (24.4) minutes, respectively (p < 0.001)). The rate of postoperative complications was similar between the two techniques., Conclusion: This study shows that FIL-SSF achieves better refractive results than iris-claw lens, with a similar rate of postoperative complications. As a relatively new implantation technique, there is a learning curve required to reduce operating time., Key Messages: What is known? Multiple surgical options for correcting aphakia in the absence of capsular support can be used. Currently, foldable intraocular lens sutureless scleral fixated sutureless (FIL-SSF, Carlevale®) and iris-claw (Artisan®) implants are the two preferred options, but there is no consensus on the best technique to adopt. What is new? We showed that FIL-SSF has a significantly lower surgically induced astigmatism compared to the iris-claw implant. Similar rate of postoperative complications was found between these two techniques. Future studies with a longer follow-up period are needed to ascertain its tolerance., Competing Interests: Declarations Ethical approval An international review board approved the study (Ethics Committee of the French Society of Ophthalmology, IRB 00008855 Société Française d’Ophtalmologie IRB#1). Informed consent Informed consent was obtained from all individual participants included in the study. Disclosure of potential conflicts of interest No Conflicts of Interest.All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript. Research involving human participants All procedures performed in studies involving human participants were in accordance with the ethical standards of the French Society of Ophthalmology, and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Competing interests The authors declared no potential conflicts of interest., (© 2024. The Author(s).)

Intravitreal anti-vascular endothelial growth factor (VEGF) therapy is the standard of care for diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD); however, vision gains and anatomical improvements are not sustained over longer periods of treatment, suggesting other relevant targets may be needed to optimize treatments. Additionally, frequent intravitreal injections can prove a burden for patients and caregivers. Angiopoietin-2 (Ang-2) has been explored as an additional therapeutic target, due to the involvement of Ang-2 in DME and nAMD pathogenesis. Recent evidence supports the hypothesis that targeting both VEGF and Ang-2 may improve clinical outcomes in DME and nAMD compared with targeting VEGF alone by enhancing vascular stability, resulting in reduced macular leakage, prevention of neovascularization, and diminished inflammation. Faricimab, a novel bispecific antibody that targets VEGF-A and Ang-2, has been evaluated in clinical trials for DME (YOSEMITE/RHINE) and nAMD (TENAYA/LUCERNE). These trials evaluated faricimab against the anti-VEGFA/B and anti-placental growth factor fusion protein aflibercept, both administered by intravitreal injection. In addition to faricimab efficacy, safety, and pharmacokinetics, durability was evaluated during the trials using a treat-and-extend regimen. At 1 year, faricimab demonstrated non-inferior vision gains versus aflibercept across YOSEMITE/RHINE and TENAYA/LUCERNE. In YOSEMITE/RHINE, faricimab improved anatomic parameters versus aflibercept. Reduction of central subfield thickness (CST), and absence of both DME and intraretinal fluid were greater in faricimab- versus aflibercept-treated eyes. In TENAYA/LUCERNE, CST reductions were greater for faricimab than aflibercept at the end of the head-to-head phase (0-12 weeks), and were comparable with aflibercept at year 1, but with less frequent dosing. CST and vision gains were maintained during year 2 of both YOSEMITE/RHINE and TENAYA/LUCERNE. These findings suggest that dual Ang-2/VEGF-A pathway inhibition may result in greater disease control versus anti-VEGF alone, potentially addressing the unmet needs and reducing treatment burden, and improving real-world outcomes and compliance in retinal vascular diseases. Long-term extension studies (RHONE-X, AVONELLE-X) are ongoing. Current evidence suggests that dual inhibition with faricimab heralds the beginning of multitargeted treatment strategies inhibiting multiple, independent components of retinal pathology, with faricimab providing opportunities to reduce treatment burden and improve outcomes compared with anti-VEGF monotherapy., Competing Interests: Declarations. Ethics approval: This review article does not contain any studies with human participants or animals performed by any of the authors. Conflict of interest: Hansjürgen Agostini is a consultant (institutional) for Apellis, Bayer, Novartis, Roche, and Zeiss. Francis Abreu is an employee of Genentech, Inc. Caroline R. Baumal is a consultant for Alcon and employee of Apellis. Dolly S. Chang is an employee of Genentech, Inc. Karl G. Csaky is a consultant for AbbVie, Adverum, Annexon, Cognition Therapeutics, Endogena, EyeBio, Genentech, Inc., Gyroscope, Heidelberg Engineering, Johnson & Johnson, Merck, NGM Bio, Novartis Pharma AG, Ocular Therapeutix, ReNeuron, Retrotope, and Ribomic; provides contracted research for Alexion, Annexon, Boehringer Ingelheim, Genentech, Inc., Gyroscope, Iveric Bio, and NGM Bio; and is a speaker for Genentech, Inc. Anna M. Demetriades was an employee of Genentech, Inc. during development of this manuscript. Laurent Kodjikian is a consultant for AbbVie, Alimera, Bayer, Horus, Novartis, Roche, and Thea. Jennifer I. Lim is a consultant for Aura, Cognition, Eyenuk, Luxa, Opthea, Quark, Roche/Genentech, Inc., Santen, Unity, and Viridian; has received financial support from Aldeyra, Chengdu, Janssen, NGM Bio, Regeneron, Roche/Genentech, Inc., and Stealth; and is a grant recipient from Iveric Bio and Novartis. Philippe Margaron is an employee of F. Hoffmann La Roche Ltd. Jordi M. Monés has received research funds from Apellis, Ionis Pharmaceuticals, Iveric Bio, Janssen, Kodiak Sciences, Novartis, Reneuron, and Roche; is a consultant for Annexon, Apellis, Cellcure, Iveric Bio, Lineage Cell Therapeutics, Maculogix, Novartis, PerceiveBio, Reneuron, and Roche; and has equity in EyeBio, Iveric Bio, Notal Vision, and Perceive. Tunde Peto is an advisor for Alimera, Astellas, Bayer, Heidelberg, Novartis, Optomed, OPTOS, Oxurion, and Roche. Federico Ricci is an advisor for AbbVie, Allergan, Apellis, Astellas, Bayer, Biogen, MSD, Novartis, Regeneron, and Roche. Matthias Rüth is an employee of F. Hoffmann La Roche Ltd. Rishi P. Singh is a consultant for Alcon, AsclepiX, Bausch and Lomb, Genentech, Inc., Gyroscope, Novartis, and Regeneron, and has received research sponsorship from NGM Bio. Ivaylo Stoilov is an employee of Genentech, Inc. Balakumar Swaminathan was an employee of Genentech Inc. during development of this manuscript. Jeffrey R. Willis is an employee of Genentech, Inc. Peter D. Westenskow is an employee of F. Hoffmann-La Roche Ltd., (© 2024. The Author(s).)

Purpose: To assess the prognostic value of subretinal (SRF) and intraretinal fluid (IRF) localizations in type 1 macular neovascularization (MNV) due to age-related macular degeneration (AMD)., Subjects: Eyes were prospectively treated with anti-vascular epithelial growth factor (anti-VEGF) intravitreal injections (IVT) according to a Pro-Re-Nata (PRN) or Treat and Extend (TAE) regimen during 24 months. A total of 211 eyes with treatment-naïve type 1 MNV secondary to AMD were consecutively included. Eyes were divided between 2 groups according to the fluid localization: presence of SRF alone (SRF group), or presence of IRF associated or not with SRF (IRF ± SRF group)., Results: At baseline the mean BCVA was 66.2 letters. SRF was present in 94.8% of eyes, IRF in 30.8%, and both in 25.6%. Data were available for 201 eyes at 12 months, and 157 eyes at 24 months. The presence of IRF at baseline was associated with lower baseline BCVA and significantly lower BCVA at 12 months (p < 0.001) and 24 months (p < 0.001). Eyes with SRF alone displayed better visual outcomes (BCVA at month 12, SRF = 74.3 letters, IRF ± SRF = 56.9 letters). In the presence of baseline IRF, fibrosis (p = 0.03) and atrophy (p < 0.001) were more frequently found at 24 months. In a multivariate model, the presence of baseline IRF was significantly associated with lower BCVA at month 12 but not at month 24., Conclusion: In type 1 MNV, the presence of baseline IRF was associated with worse visual outcomes compared to SRF alone, and more frequent atrophy and fibrosis., (© 2024. The Author(s).)

Purpose: To investigate the variation of interleukin-10 (IL-10) levels in the aqueous humor (AH) of patients with vitreoretinal lymphoma (VRL) throughout therapy and follow-up and analyze the relation of these variations with VRL clinical course and relapse., Methods: This study retrospectively included consecutive patients diagnosed with VRL in a single center. AH IL-10 samples and patient clinical course were evaluated. The response to treatment was evaluated according to the criteria set by the International Primary Central Nervous System Lymphoma Collaborative Group., Results: A total of 59 eyes of 34 patients were included. Interleukin-10 levels decreased significantly at first AH sample after therapy induction (median [IQR] 3.0 [2.8-3.6] months) among patients in complete clinical remission (P < 0.001). Among patients in complete clinical remission with residual detectable IL-10 in AH after therapy induction (85.3% systemic chemotherapy, 11.8% intravitreal methotrexate, 2.9% palliative care), 87.5% experienced ocular relapse within 5 years. The detection of IL-10 in AH at the first visit after induction for complete clinical remission obtained a sensitivity of 77.8% (95% CI 0.45-0.96) and a specificity of 96.4% (95% CI 0.82-0.99) to predict ocular relapse. For relapsing eyes (N = 26), IL-10 significantly increased between the last IL-10 measurement and the time of the first ocular relapse (P < 0.001). In 76.0% of cases, an increase in IL-10 was detected earlier than clinical relapse with a mean (SD) of 4.0 (2.4) months., Conclusion: The present study suggested the usefulness of IL-10 in the prognosis of VRL. This study showed a relation between IL-10 in AH and tumoral activity, and for the first time with disease relapse.

Purpose: To describe the demographic and clinical characteristics of uveitis in patients with giant cell arteritis (GCA), their treatments, and evolution., Methods: A national retrospective cohort study was performed. The inclusion criteria were as follows: patients with GCA fulfilling the 2022 ACR/EULAR criteria and a diagnostic of uveitis attested by an ophthalmologist., Results: Seven women were included. The median age at diagnosis of uveitis was 71 years (64-84). All uveitis were diagnosed during active GCA (five at initial diagnosis, two at relapse). All uveitis were acute (100%), mostly anterior (86%) and bilateral (71%). Granulomatous features were less common (29%). All uveitis were treated with local and systemic corticosteroids. After a median follow-up of 30 (21-55) months, all patients achieved complete ophthalmic remission, with only one relapse at 2 years. GCA was also in complete remission., Conclusions: Uveitis could reveal GCA, and its presence correlated with disease activity of GCA. The most frequent clinical presentation of uveitis was acute and anterior; using local and systemic corticosteroids, the prognosis was favorable.

Purpose: Determining uveitis etiology is a challenge. It is based primarily on demographic data and the characteristics of eye examination. It is not clear to what extent extraocular physical signs contribute to elucidating the etiology. This study aimed to establish the contribution of the clinical extra-ophthalmological features for the assessment of the underlying etiology of uveitis., Methods: We retrospectively reviewed 1307 patients with uveitis referred to our tertiary center between 2003 and 2021. Uveitis was classified according to the Standardization of Uveitis Nomenclature. Clinical features were collected at diagnosis by internists before the etiological diagnosis was made. The main outcome description was the contribution of clinical features., Results: Clinical extra-ophthalmological features contributed to the assessment of the underlying etiology of uveitis in 363 (27.8%) patients. The joint and the skin examinations were the most useful for etiological investigations, respectively in 12.3% and 11.8% of patients. Five etiologies of uveitis accounted for 80% of the cases: sarcoidosis, HLA-B27-related uveitis, Behçet's disease, multiple sclerosis, and Vogt-Koyanagi-Harada disease. Clinical extra-ophthalmological features were particularly important in the etiological diagnosis of acute bilateral anterior uveitis and panuveitis., Conclusion: This study suggests that clinical extra-ophthalmological features are essential for the etiological diagnosis of uveitis in more than a quarter of patients. It demonstrates once again the value of collaboration between ophthalmologists and other specialists experienced in performing extra-ophthalmological clinical examinations, particularly in patients with acute bilateral anterior uveitis and panuveitis.

Purpose: To assess subretinal fibrosis (SF) occurrence in neovascular age-related macular degeneration (nAMD), according to macular neovascularisation (MNV) subtypes., Methods: A Retrospective national multi centre cohort study included eyes with naive nAMD. Main outcome measures were, according to MNV subtypes, cumulative incidence for SF, risk factors, and best corrected visual acuity (BCVA) for 36 months., Results: Four hundred and twenty eyes were included. Cumulative incidence of SF was 34.3% at 1 year, 39.0% at 2 years and 50.6% at 3 years. In multivariable analysis, Type 2 and mixed type 1 and 2 MNV were associated (p < 0.001) with a more frequent and rapid development of SF (respectively 85.5% and 81.0% at 1 year, then 95.8% and 93.1% at 3 years) than Types 1 and 3 (respectively 11.3% and 3.6% at 1 year, then 22.9% and 12.7% at 3 years). In Type 2 and mixed type 1 and 2 MNV combined, at baseline a worse BCVA (p = 0.02) and a higher maximal subretinal hyperreflective material (SHRM) thickness (p = 0.005) were associated with SF development at 3 years. In Type 1 MNV, the presence at baseline of intraretinal fluid (IRF) (p = 0.007) or SHRM (p < 0.001) and a higher percentage of visits with IRF (p < 0.001) or with SHRM (p < 0.001) were associated with SF occurrence. For Type 3 MNV, only a higher percentage of visits with SHRM (p = 0.001) was associated with SF. Including all MNV subtypes, eyes with a worse BCVA at baseline were associated with SF development (p < 0.001). Conversely, presence of SF at 3 years was associated with a worse baseline BCVA (p < 0.001)., Conclusion: Occurrence of SF differs when considering apart MNV subtypes., (© 2024 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Diabetic macular edema (DME) is a common complication of diabetic retinopathy. Treatment with intravitreal injections is effective in most cases but is associated with a high therapeutic burden for patients. This implies the need for long-term treatments, such as the fluocinolone acetonide (FAc) implant. A review of basic science, pharmacology, and clinical data was conducted to provide a state-of-the-art view of the FAc implant in 2024. Although generally well tolerated, the FAc implant has been associated with ocular hypertension and cataract, and caution should be advised to the patients in this regard. By synthesizing information across these domains, a comprehensive evaluation can be attained, facilitating informed decision-making regarding the use of the FAc implant in the management of DME. The main objective of this review is to provide clinicians with guidelines on how to introduce and use the FAc implant in a patient with DME.

Purpose: To assess the effectiveness of switching intravitreal dexamethasone implants (DEX-implant) from pro re nata (PRN) treatment regimen to a proactive regimen in patients with macular edema of diverse etiologies., Design: An observational, retrospective, uncontrolled, multicenter, national case series., Participants: Eighty-one eyes from 68 patients treated between October 2015 and June 2023 were included., Methods: This study included consecutive eyes treated with DEX-implant who were switched from a PRN regimen to a proactive regimen for diabetic macular edema (DME), retinal vein occlusion (RVO), noninfectious uveitis macular edema (UME; including postsurgical macular edema), and radiation maculopathy (RM)., Main Outcome Measures: The main outcome measures were change in the best-corrected visual acuity (BCVA), central macular thickness (CMT), and intraocular pressure (IOP) at each visit., Results: According to the etiology, DME represented 49.4% of eyes, UME 24.3%, RVO 21.0%, and RM 6.2%. The mean (standard deviation [SD]) duration of follow-up under the PRN and proactive regimens was 20.6 (13.3) and 14.2 (10.3) months, respectively. Switching from a PRN to a proactive regimen significantly improved mean (SD) BCVA by 3.7 (12.9) ETDRS letters (P = 0.01) with a mean (SD) decrease in CMT of 108.0 (151.4) μm (P < 0.001). The proportion of visits with significant anatomic recurrence (> 50 μm) also decreased from 40.1% to 6.0% after switching to a proactive regimen (P < 0.001). The number of DEX-implant injections significantly increased during the proactive treatment period (P < 0.001), but the change in the number of visits was not significantly different (P = 0.2). The proactive treatment period was not associated with a significant increase in IOP (P = 0.6)., Conclusions: Switching to a proactive regimen in patients already treated with DEX-implant seems to significantly improve BCVA and CMT while maintaining stable IOP., Financial Disclosures: 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.)

Spondyloarthritis (SpA) encompasses a group of chronic inflammatory disorders of the joints frequently associated with uveitis in almost a quarter of cases. SpA-related uveitis typically affects the eye anterior chamber with sudden onset, causing pain, redness, photophobia, and blurred vision. Ophthalmologists will describe an acute anterior unilateral uveitis. Most patients present with episodic acute anterior non-granulomatous uveitis and retain excellent visual acuity. However, systemic treatments are recommended in the event of frequent relapses (2-3/year) or in rare cases of sight-threatening with ocular complications. The improved understanding of the pathogenesis of SpA has led to the management of this disease by biologics. Here, we review the main data regarding the opportunity to target specific components in inflammatory pathways for the treatment of SpA-related uveitis. These therapies are recommended for long-term control when uveitis relapses occur too frequently despite conventional systemic treatments. Significant benefits have been obtained with the tumor necrosis factor-α inhibitors (TNFis), particularly infliximab and adalimumab. Paradoxically, a high number of uveitis occurrences have been shown on etanercept. Mixed results have been demonstrated with interleukin-17 antagonists (secukinumab) and interleukin-12/interleukin-23 antagonists (ustekinumab) in cases of failure of TNFis. JAK inhibitors seem to be a valuable class of medications for these patients in the future. Although SpA-related uveitis is typically managed with conventional local and/or systemic treatments, these biological/targeted therapies may provide avenues to control both the underlying SpA and uveitis manifestations. Thus, a close collaboration between patients, rheumatologists, internists, and ophthalmologists is needed to optimally manage ocular inflammation in SpA., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Aims: To compare effectiveness of subconjunctival triamcinolone acetonide injections and intravitreal injections of dexamethasone 700 µg implants in reducing central macular thickness (CMT) in uveitic and postoperative macular oedema (ME)., Methods: We conducted an open-label, French multicentre randomised comparative trial with a logarithmic CMT non-inferiority margin set at 0.06. Patients were adults with non-infectious inflammatory ME, without any contraindication to the treatments. They were randomised 1:1 to receive either triamcinolone or dexamethasone. The primary endpoint was the difference in CMT among treated eyes between baseline and 2 months, measured with spectral-domain optical coherence tomography. Secondary outcomes included visual acuity, laser flare, vitreous haze, duration of action, tolerance to injections and adverse events., Results: Between January 2016 and January 2020, 106 patients were enrolled (54 in the triamcinolone group and 52 in the dexamethasone group). Subconjunctival triamcinolone injections seemed to be non-inferior to intravitreal dexamethasone injections, especially at month 3 (and nearly at month 1). Nevertheless, we could not demonstrate it, with a treatment effect at month 2 of 0.05 (0.01 ; 0.09) (p value=0.001). This was corroborated by post hoc analyses in the postoperative subgroup, for whom the non-inferiority was nearly demonstrated at month 2 with a treatment effect of 0.02 (-0.03 ; 0.08) (p=0.37). There was no significant difference in the occurrence of adverse effects., Conclusion: We could not demonstrate the non-inferiority of triamcinolone injections at month 2. Nevertheless, they showed some efficacity, particularly in treating postoperative ME, being as safe as dexamethasone injections, without any loss of chance if a therapeutic switch is necessary., Competing Interests: Competing interests: M-AV: data safety monitoring board member in Comité de Protection des Personnes—Ouest IV since september 2022. Payment for expert testimony by Institut National du Cancer in 2023. BB: grants/contracts with Horus Pharma, AbbVie/Allergan. Consulting fees by Horus Pharma, AbbVie/Allergan, Novartis, Active Biotech, Acelyrin, Roche. Advisory board for Genesight. ML: consulting fees/honoraria/payments for expert testimony by Alcon, Allergan, Bausch & Lomb, DMG, Dompe, Horus Pharma, MSD, Novartis, Quantel, Santen, Shire, Topivert, Théa. Support for attending meetings and/or travel by Bausch & Lomb, Novartis, Théa. M-BR: consulting fees/honoraria/support fort attending meetings by Allergan, Horus Pharma. KA: advisory board in uveitis for Horus Pharma. CChiquet : consulting fees for AbbVie, Amo, Horus Pharma, Théa. Advisory board for Horus Pharma. LK: consulting fees/honoraria by AbbVie, Alimera, Bayer, Novartis, Roche, Théa. Support for attending meetings and/or travel by AbbVie, Bayer, Novartis. Advisory board for Alimera, Bayer, Horus Pharma, Novartis. SB: honoraria by Abbvie, Horus Pharma, Novartis, Roche. Supporting for attending meetings and/or travel by Abbvie, Bayer, Roche. Advisory board for AbbVie, Bayer, Horus Pharma. CPC-G: grants/contracts for the institution with Bayer, Novartis. Consulting fees by AbbVie/Allergan, Alcon, Apellis Pharmaceuticals, Bayer, Horus Pharma, Novartis, Roche, Théa. Honoraria and support for attending meetings and/or travel by Allergan, Bayer, Novartis, Roche. MW: consulting fees/honoraria by AbbVie., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To determine the efficacy and safety of brolucizumab therapy administered on a pro re nata (PRN) basis without loading dose in treatment naïve patients with diabetic macular edema (DME) for 1 year follow-up., Methods: Patients with recent DME (<6 months) received a mandatory brolucizumab injection at inclusion and other injections could be given on a PRN basis with an 8-week interval (between injections) at minimum. Rescue therapy with other anti-VEGF was possible in case of incomplete DME resolution after the second brolucizumab with a minimum of 1-month treatment free interval between 2 injections. The primary outcome measure was the change in (BCVA) at 12 months. Secondary outcome measures included the change in central subfield thickness (CST), the change in hard exudate surface area and microaneurysms at 1 year., Results: A total of 53 patients were included. At 12 months, the mean (SD) number of injections was 2.6 (0.8) in addition to the first mandatory injection. The mean (SD) interval between 2 consecutive injections was 3.2 (1.4) months. The mean (SD) BCVA improved from 0.62 (0.1) logMAR to 0.40 (0.16) logMAR (p = 0.012). The mean CST reduced from 397.0 (47.2) µm to 224.5 (28.1) µm (p = 0.013). The hard exudate surface area decreased significantly (p = 0.012) as did microaneurysms (p = 0.02). Seven patients required at least 1 rescue therapy. No patients experienced intra-ocular inflammatory adverse events., Conclusion: Brolucizumab therapy for DME is a safe and effective modality for the treatment of recent DME and has the potential to reduce the number of injections.

Purpose: This clinical investigation compared the performance and safety of Eyestil Plus® (SIFI) and Vismed Multi® (TRB Chemedica) for reducing keratitis lesions in moderate-to-severe dry eye disease (DED) patients., Materials and Methods: This was a randomised, double-blind, multicentre investigation. 96 adults (>18 years of age) with moderate-to-severe DED received Eyestil Plus® ( N  = 48) or Vismed Multi® ( n  = 48) 6 times daily for 3 months. The primary objective clinical performance after 1 month as global corneal and conjunctival staining scores. The secondary objectives were clinical performance after 3 months, tear film stability (tear break up time (TBUT), tear production (Schirmer test), patient-reported outcomes (PROs), investigator satisfaction, and safety., Results: 96 participants were randomised to receive the clinical investigations' treatments, 82.3% of them were female and their mean age was 65.8 years. The non-inferiority of Eyestil Plus® for moderate-to-severe DED was demonstrated at 1 month. No statistical difference was found for any of the study's objectives: change at 1 and 3 months of the global corneal and conjunctival staining score ( p -value = 0.506 and 0.661, respectively), change at 1 and 3 months ( p -value = 0.538 and 0.302) for TBUT test; change at 3 months for Schirmer test ( p -value = 0.540). There were no changes for PROs either. Investigator satisfaction was high for both products. 16.6% of the participants experienced adverse events., Conclusion: This clinical investigation showed the non-inferiority of Eyestil Plus® compared to Vismed Multi® regarding performance and safety in a moderate-to-severe DED population., 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.

Neovascular age-related macular degeneration (nAMD) remains a major cause of visual impairment and puts considerable burden on patients and health care systems. l-DOPA-treated Parkinson's disease (PD) patients have been shown to be partially protected from nAMD, but the mechanism remains unknown. Using murine models that combine 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced (MPTP-induced) PD and laser-induced nAMD with standard PD treatment of l-DOPA/DOPA-decarboxylase inhibitor or specific dopamine receptor inhibitors, we here demonstrate that l-DOPA treatment-induced increase of dopamine-mediated dopamine receptor D2 (DRD2) signaling inhibits choroidal neovascularization independently of MPTP-associated nigrostriatal pathway lesion. Analyzing a retrospective cohort of more than 200,000 patients with nAMD receiving anti-VEGF treatment from the French nationwide insurance database, we show that DRD2 agonist-treated PD patients have a significantly delayed age of onset of nAMD and reduced need for anti-VEGF therapies, similar to the effects of the l-DOPA treatment. While providing a mechanistic explanation for an intriguing epidemiological observation, our findings suggest that systemic DRD2 agonists might constitute an adjuvant therapy to delay and reduce the need for anti-VEGF therapy in patients with nAMD.

Background: Non-infectious uveitis affecting the posterior segment of the eye (NIU-PS) is an inflammatory disease, which can significantly impair visual acuity if not adequately treated. Fluocinolone-acetonide sustained-release-0.2 µg/day intravitreal (FAc) implants are indicated for prevention of relapse in recurrent NIU-PS. The aim here was to provide treating clinicians with some consensus-based-recommendations for the clinical management of patients with NIU-PS with 0.2 µg/day FAc implants., Methods: A European-clinical-expert-group agreed to develop a consensus report on different issues related to the use of FAc implants in patients with NIU-PS., Results: The Clinical-expert-panel provided specific recommendations focusing on clinical presentation (unilateral/bilateral) of the NIU-PS; systemic involvement of NIU-PS and the lens status. Treatment algorithms were developed; one that refers to the management of patients with NIU-PS in clinical practice and another that establishes the best clinical scenarios for the use of FAc implants, both as monotherapy and as adjuvant therapy. Additionally, the Clinical-expert-panel has provided recommendations about the use of the FAc implants in a clinical-setting. The Clinical-expert-panel also considered the safety profile of FAc implants and their possible implications in the daily practice., Conclusions: As more clinical experience has been gained using FAc implants, it was necessary to update the clinical recommendations that guide patient management in the clinic. The current consensus document addresses relevant issues related to the use of FAc implants on different types of patients with various etiologies of NIU-PS, and was conducted to standardize approaches to help specialists obtain better clinical outcomes., (© 2024. The Author(s).)

Purpose: To report three cases of postoperative opacification of sutureless scleral-fixed hydrophilic intraocular lens (FIL SSF IOL, Soleko, Italy) after gas tamponade. Two cases occurred after pars plana vitrectomy and one case after Descemet membrane endothelial keratoplasty., Case Report: Two diabetic patients underwent a FIL SSF IOL implantation after posterior capsular rupture during cataract surgery. Rhegmatogenous retinal detachment (RRD) was observed in one patient during the initial surgery. A second patient developed a RRD five months after surgery. Both RRDs were treated with pars plana vitrectomy and perfluoroethane (C2F6) gas tamponade. A few days after the surgery, C2F6 was observed in the anterior chamber of both patients. Two months after gas tamponade, opacification of the anterior surface of the IOL was observed. The third patient was a 74-year-old woman, who underwent a combined Descemet membrane endothelial keratoplasty (DMEK) and FIL SSF IOL implantation. Two rebubblings with sulfur hexafluoride (SF6) retreatments were required due to corneal graft detachment. One month later, an opacification of the anterior surface of the IOL was observed. Explantation with implantation of iris-claw IOL was decided, which resulted in an improvement of BVCA. Analysis of the IOL showed a positive Von Kossa staining, indicating calcification of the IOL. We performed a review of all the cases of FIL SSF IOL implantation in our centers. The overall rate of FIL SSF IOL opacification was 2.1% (3/140). Amongst patients treated with gas tamponade, the rate of opacification was 27.3% (3/11). Although FIL SSF IOL implantation appears to be an effective option for the treatment of aphakia, caution should be exercised regarding the risk of opacification following gas tamponade, especially since these patients are at risk of retinal detachment., 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.

Background: To determine long-term efficacy and safety of intravitreal brolucizumab therapy for neovascular age-related macular degeneration (nAMD) in the real-world setting., Methods: Retrospective, observational, multicentric study and an extension of the REBA study (Real-world Experience with Brolucizumab in nAMD) to 24 months. The study entailed follow-up of 91 consecutive eyes (67 patients) with nAMD who received brolucizumab therapy and completed 24 months of follow-up. Both treatment-naïve and switch therapy patients were included. All relevant data were collected. The primary outcome measure was changed in best-corrected visual acuity (BCVA) over time. Secondary outcome measures included change in central subfield thickness (CST) and complications., Results: The mean (SD) baseline BCVA was 48.4 (3.5) letters and 36.2 (7.1) letters in treatment-naïve group and switch therapy group, respectively. BCVA gain was + 9.2 (3.7) letters (p = 0.01) and + 7.7 (3.4) letters (p = 0.011), respectively. The change in mean (SD) CST has shown a significant decrease in retinal thickness in treatment-naïve group (from 432.5 (68.4) to 283.0 (51.3) µm; p = 0.018) and in switch therapy group (from 452.5 (40.5) to 271.0 (43.4) µm; p = 0.011) group. One switch patient developed vascular occlusion and another a macular hole after the fifth brolucizumab injection as reported in the primary study. Both patients recovered uneventfully. Three patients demonstrated reversible intraocular inflammation between months 10 and 24., Conclusion: Patients showed a significant anatomical and functional response to brolucizumab therapy in the real world, regardless of prior treatment status, until the end of the follow-up period. Overall, 5 significant untoward events were noted., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: AZURE was a 76-week, randomized, open-label, parallel-group, phase IIIb noninferiority study comparing the efficacy and safety of intravitreal aflibercept (IVT-AFL) in a treat-and-extend (T&E) regimen with fixed dosing in patients with neovascular age-related macular degeneration (nAMD) previously receiving IVT-AFL for ≥ 1 year., Methods: Patients were aged ≥ 51 years and had completed ≥ 1 year of IVT-AFL treatment prior to enrollment (IVT-AFL once per month [- 1 or + 2 weeks] for 3 months followed by IVT-AFL every 2 months [6-12 weeks]). Patients were randomly assigned (1:1) to receive IVT-AFL 2 mg in either a T&E (minimum treatment interval of 8 weeks with no upper limit, adjusted according to functional and anatomic outcomes, as assessed by the investigator; n = 168), or a fixed dosing regimen (treatment every 8 weeks [± 3 days]; n = 168). The primary endpoint was best-corrected visual acuity (BCVA) change from baseline to week (W) 52. The key secondary endpoint was the proportion of patients maintaining vision (< 15-letter loss) at W52., Results: The full analysis set comprised 332 patients (T&E: n = 165; fixed dosing: n = 167). Mean BCVA change (baseline to W52) was - 0.3 ± 7.5 vs. - 0.5 ± 8.4 letters (T&E vs. fixed dosing; least-squares mean difference [95% CI]: 0.22 [- 1.51 to 1.96] letters; P < 0.0001 for noninferiority test [5-letter margin]). From baseline to W52, 95.2% (T&E) and 94.0% (fixed dosing) of patients maintained vision. Mean central subfield thickness change from baseline to W52 was - 24 ± 55 (T&E) and - 33 ± 47 (fixed dosing) µm. Last treatment interval to W76 was ≥ 12 weeks for 37.0% of T&E patients. No new safety signals were identified., Conclusion: IVT-AFL T&E can achieve similar functional and anatomic outcomes to fixed dosing every 8 weeks over 52 weeks in patients with nAMD who have completed ≥ 1 year of treatment, while reducing treatment burden., Trial Registration: ClinicalTrials.gov Identifier: NCT02540954., (© 2024. The Author(s).)

Purpose: To evaluate the safety and efficacy of the fluocinolone acetonide implant (FAi, Iluvien ® Horus pharma, Nice, France) in non-infectious uveitic macular edema (UME) and to approach the predictive factors of treatment response., Methods: This retrospective, multicenter real-life study included patients with chronic non-infectious UME who received intravitreal FAi after at least two dexamethasone implants (DEXi)., Results: Twenty-six eyes from 22 patients (73.1% of females) were included. The mean age was 60.4 ± 16 years. The mean follow-up was 11.4 ± 2 months. The mean baseline best-corrected visual acuity (BCVA) was 0.43 ± 0.36 LogMAR, improving significantly after 1, 3, 6 and 12 months (all p < 0.05 vs. baseline). The mean baseline central macular thickness (CMT) was 429 ± 110 μm, improving significantly after 1, 3, 6 and 12 months (all p < 0.05 vs. baseline). Five eyes (19.2%) developed ocular hypertension during the follow-up, requiring initiation or strengthening of intraocular pressure lowering medication. The majority of eyes (77%) did not require any rescue DEXi during the available 12-month follow-up. The resolution of UME after DEXi seemed to predict the anatomical response after FAi. The baseline presence of a disorganization of the inner retinal layers (DRIL) and hyperreflective foci (HRF) were both associated with a higher likelihood of requiring rescue DEXi injections., Conclusion: FAi implantation led to a significant BCVA and CMT improvement with a good safety profile over the 12-month follow-up. Predictive factors of treatment outcomes seem to include the anatomical response to DEXi and the presence of DRIL and HRF at baseline.

Background/purpose: To assess the efficacy and tolerance of hydroxychloroquine in sarcoidosis-associated uveitis., Methods: Retrospective study on all patients with sarcoidosis-associated uveitis who were treated with hydroxychloroquine between 2003 and 2019 in a French university hospital., Results: Twenty-seven patients with sarcoidosis-associated uveitis received hydroxychloroquine. The mean duration of treatment was 20.0 ± 10.9 months. At the end of the follow-up, hydroxychloroquine success was achieved in 15 (55.6%) patients. Four of them were also on oral corticosteroids, with a prednisone dose ≤5 mg/day. Under treatment, the median prednisone dose decreased from 20.0 (interquartile range (IQR), 7-25) to 5.0 (IQR, 3-6.5) mg/day ( p  = .02). The incidence rate of flare decreased from 204.6 to 63.8 per 100 person-years ( p  = .02). Hydroxychloroquine was discontinued in 12 (44.4%) patients during follow-up, including 8 (29.6%) for ineffectiveness, and three who experienced side effects., Conclusion: Hydroxychloroquine appears as an interesting option in sarcoidosis-associated uveitis. Abbreviations: AZA: Azathioprine; BAL: Bronchoalveolar Lavage; BCVA: Best-Corrected Visual Acuity; ENT: Ears, Nose and Throat; HCQ: Hydroxychloroquine; IOP: Intra-Ocular Pressure; IQR: interquartile range; MHC: Major Histocompatibility Complex; MMF: Mycophenolate Mofetil; MTX: Methotrexate; PMSI: Programme de Médicalisation du Système d'Information; SAU: Sarcoidosis-Associated Uveitis; SD: Standard Deviation; SUN: Standard Uveitis Nomenclature.

Background: To evaluate the contribution of chest X-ray and chest CT for the diagnosis of sarcoid uveitis., Methods: Retrospective study on consecutive patients with uveitis of unknown etiology, who underwent both chest X-ray and CT during uveitis diagnosis workup in a tertiary French university hospital., Results: A total of 914 patients were included. Systemic sarcoidosis was identified in 23.1%. The probability of discordance between chest X-ray and CT increased with age at diagnosis ( p  < 0.001). In patients 30 years of age and younger, the probability of discordance was 5% or less, and 0.8% if the ACE level was normal. After 78.3 years of age, the probability of discordance was 20% or more., Conclusion: We recommend not to perform CT in patients under 30 years of age with a normal chest X ray and ACE level, and suggest performing chest CT first in the elderly.

Introduction: Retinal cavernous hemangioma (RCH) is a rare retinal vascular disease characterized by grape-like clusters of saccular aneurysms, usually unilateral, asymptomatic and non-progressive. The diagnosis is made by multimodal imaging including conventional fluorescein angiography (FA). The recent introduction of swept source optical coherence tomography angiography (SS-OCTA) has allowed new insight into vascular diseases, allowing non-invasive, more precise visualization of retinal and choroidal blood flow, and represents a possible alternative to FA., Methods: We herein describe two cases of RCH with multimodal imaging, including SS-OCTA, and compare our findings with those previously described., Results: On OCTA, the presence of a draining vessel, a reduction in flow signal in the SCP and DCP, and a fluid level can be observed., Conclusion: These OCTA signs are in accordance with those described on conventional fluorescein angiography, allowing this invasive exam to be avoided in typical cases., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Purpose: To present interim descriptive insights from the OCTOPUS and SWIFT studies on incidence, clinical features, management, and outcomes of intraocular inflammation (IOI), vasculitis, and occlusive vasculitis with brolucizumab treatment (Beovu, Novartis) in patients with neovascular age-related macular degeneration (nAMD) who were anti-VEGF naive or pretreated with anti-VEGFs (ranibizumab or aflibercept)., Design: OCTOPUS (NCT04239027) and SWIFT (NCT04264819) studies are prospective phase IIIb single-arm, open-label, multicenter studies assessing brolucizumab., Subjects: Anti-VEGF naive (OCTOPUS) and pretreated (SWIFT) patients with nAMD., Methods: Interim prespecified analysis on the efficacy end point provided an opportunity to analyze IOI-related safety. Reports of IOI-related adverse events (AEs) were reviewed, and AE images and clinical features and outcomes of each case were analyzed by a review committee., Results: Of 505 brolucizumab-treated eyes/patients with median brolucizumab treatment of 8.8 months, 53 eyes demonstrated at least 1 IOI-related AE. The incidence of overall IOI-related AEs was 10.5%; among these events, the incidence was 7.1% for IOI only without retinal involvement and 3.4% for IOI with retinal involvement (2.0% with vasculitis, 1.4% with vascular occlusion with or without vasculitis). Incidence was similar in naive and pretreated patients. Before the onset of the first IOI-related AE, eyes received a median of 2 brolucizumab injections; 81.1% of IOI-related AEs occurred during the loading phase (median, 25.0 days from the last brolucizumab injection). At AE onset, most frequently reported symptoms were floaters (52.8%) and blurred or decreased vision (37.8%). Of the 86.8% of AEs that were treated, most were treated with topical corticosteroids (75.5%), 28.3% by systemic corticosteroids, and 26.8% by intraocular corticosteroids. No severe vision loss was reported for the 7 nontreated AEs. Overall, the median best-corrected visual acuity (BCVA) change at IOI-related AEs resolution from baseline was 1 letter (range, -74 to +32 letters), and 2 patients with occlusive vasculitis had BCVA loss ≥ 15 letters due to IOI-related AEs. All eyes permanently discontinued brolucizumab after the first IOI-related AE., Conclusions: This analysis highlights the need for monitoring and education of patients to report any signs of IOI-related events immediately when being treated with brolucizumab. IOI should be treated promptly and intensely with corticosteroids., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

These guidelines are a consensus of French glaucoma and retina experts on the management of ocular hypertension (OHT) observed in a third of the cases after corticosteroid implant intravitreal injections. They update the first guidelines published in 2017. Two implants are marketed in France: the dexamethasone implant (DEXi) and the fluocinolone acetonide implant (FAci). It is essential to assess the pressure status before injecting a patient with a corticosteroid implant. A molecule-specific monitoring of the intraocular pressure is needed throughout the follow-up and at the time of reinjections. Real-life studies have allowed optimizing the management algorithm by significantly increasing the safety of these implants. Corticosteroid testing with DEXi should be performed before switching to FAci to optimize pressure tolerance of FAci. Beyond topical hypotensive treatments, selective laser trabeculoplasty may be considered in the therapeutic arsenal for the management of steroid-induced OHT and subsequent injections., (Copyright © 2023. Published by Elsevier Masson SAS.)

Geographic atrophy (GA) is a progressive and irreversible retinal disease with no comprehensive recommendations for diagnosis or monitoring. We used a Delphi approach to determine consensus in key areas around diagnosis and management of GA. A steering committee of eight retina specialists developed two sequential online surveys administered to eye care professionals (ECPs). Consensus was defined as agreement by ≥ 75% of respondents. Up to 177 ECPs from eight countries completed one or both surveys. Consensus was achieved in several topics related to diagnostic imaging, including the use of optical coherence tomography, and the urgent need for treatments and beneficial interventions to reduce the associated burden. Currently, low-vision aids and smoking cessation are considered the most beneficial interventions. We demonstrate consensus for diagnosis and management of patients with GA including best practices in patient identification and monitoring, and unmet needs. [ Ophthalmic Surg Lasers Imaging Retina 2023;54:589-598.] .

These are the recommendations of French glaucoma and retina experts on the management of ocular hypertension (OHT) observed in 1/3 of cases after intravitreal steroid implant injections. They are an update to the recommendations first published in 2017. There are two implants on the French market: the dexamethasone (DEXi) and fluocinolone acetonide (FAci) implants. It is important to know the pressure status before injecting a patient with a steroid implant. Monitoring of the IOP adapted to the specific drug is necessary throughout follow-up and reinjections. Real-life studies have made it possible to optimize the management algorithm by significantly increasing the safety of use of these implants. A corticosteroid test with DEXi is necessary before switching to FAci to optimize the pressure tolerance of the latter. In addition to topical glaucoma medications, SLT laser can be considered in the therapeutic arsenal for the management of steroid-induced OHT and future injections., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Purpose: To compare the efficacy and the safety of submacular hemorrhage (SMH) management using either surgical pars plana vitrectomy (PPV) or pneumatic displacement (PD) with tissue plasminogen activator (tPA) and vascular endothelial growth factor (VEGF) inhibitor added to each arm., Design: Randomized, open-label, multicenter superiority study., Participants: Ninety patients with neovascular age-related macular degeneration (nAMD) 50 years of age or older with recent SMH (≤ 14 days) of more than 2 optic disc areas and predominantly overlying the retinal pigment epithelium., Methods: Patients were assigned randomly to surgery (PPV, subretinal tPA [maximum, 0.5 ml/50 μg], and 20% sulfur hexafluoride [SF 6 ] tamponade) or PD (0.05 ml intravitreal tPA [50 μg] and 0.3 ml intravitreal pure SF 6 ). Both groups were asked to maintain a head upright position with the face forward at 45° for 3 days after intervention and received 0.5 mg intravitreal ranibizumab at the end of the intervention, at months 1 and 2, as the loading phase, and then on a pro re nata regimen during a 6-month follow-up., Main Outcome Measures: The primary efficacy endpoint was mean best-corrected visual acuity (VA) change at month 3. The secondary endpoints were mean VA change at month 6, 25-item National Eye Institute Visual Function Questionnaire composite score value at months 3 and 6, number of anti-VEGF injections, and complications during the 6-month follow-up., Results: Of the 90 patients randomized, 78 patients (86.7%) completed the 3-month efficacy endpoint visit. The mean VA change from baseline to month 3 in the surgery group (+16.8 letters [95% confidence interval (CI), 8.7-24.9 letters]) was not significantly superior to that in the PD group (+16.4 letters [95% CI, 7.1-25.7 letters]; adjusted difference β, 1.9 [-11.0; 14.9]; P = 0.767). Both groups achieved similar secondary outcomes at month 6. No unexpected ocular safety concerns were observed in either group., Conclusions: Surgery did not yield superior visual gain nor additional benefit for SMH secondary to nAMD compared with PD at 3 months, with intravitreal anti-VEGF added to each arm. Both treatment strategies lead to a clinical improvement of VA without safety concerns for SMH over 6 months. Both design and results of the trial cannot be used to establish equivalence between treatments., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of interests PS declares competing interests with Abbvie and Chugai. LK declares competing interest with Abbvie, Novartis, Bayer, Roche, Alimera, Horus, and Thea. All other authors declare no competing interests.