Corneal Toxicity in Patients Treated by BELANTAMAB MAFODOTIN: How to Improve and Facilitate Patients Follow-Up Using Refractive Shift?

Purpose: Multiple myeloma (MM) is the second most common neoplastic blood disease worldwide. Belantamab mafodotin is a new antibody conjugate anti-B-cell maturation antigen effective against refractory myelomas. It induces intracorneal microcysts leading to refractive fluctuations. The aim of this study is to assess the value of monitoring refractive fluctuations based on the location of microcystic-like epithelial changes (MECs) to facilitate patient follow-up. Methods: This observational and multicentric study was conducted using data collected from several French centers contacted through secure email through a standardized data collection table. Results: The fluctuation of objective refraction in spherical equivalent confirms a significant myopic shift from peripheral to central forms. A decrease in the best-corrected visual acuity (BCVA), an increase in keratometry, and an increase in central epithelial pachymetry have also been observed when MECs migrate toward the center. Conclusion: The myopization found in our study in patients with central and paracentral MECs is consistent with current literature. Fluctuations in BCVA, keratometry, and epithelial pachymetry are also consistent. This study is the first real-world study and highlights heterogeneity in follow-up, emphasizing the need to establish multidisciplinary follow-up strategies. The analysis of refractive fluctuations appears to be a reproducible and noninvasive screening method that could facilitate patient follow-up without the need for consultation focused on corneal diseases.

Two-year outcomes of Xen 45 gel stent implantation in patients with open-angle glaucoma: real-world data from the Fight Glaucoma Blindness registry.

OBJECTIVE: To evaluate efficacy and safety outcomes of the Xen 45 gel stent implant over 24 months of follow-up. METHODS: A retrospective analysis of prospectively collected data from the Fight Glaucoma Blindness observational registry. Complete success (CS) was defined as intraocular pressure (IOP) reduction ≥20% from preoperative and an IOP ≤18 mm Hg and ≥6 mm Hg with no secondary procedure at 2 years and without IOP-lowering medications. Qualified success (QS) was defined similarly, allowing the use of IOP-lowering medications. RESULTS: The Xen 45 gel stent implant was implanted in 646 eyes of 515 patients. Preoperative IOP was 21.4±7.6 (mean±SD) mm Hg on 2.7±1.3 IOP-lowering medication and mean deviation was -10.2±8.4 dB. After 24-month follow-up, IOP was 16.8±7.3 mm Hg (mean reduction of 21.7%) on 1.2±1.4 IOP-lowering medications. CS and QS rates at 24 months were 26% and 48%, respectively. CS and QS were higher in the Xen stand-alone group (33% and 52%, respectively) than in the Xen+cataract group (16% and 42%, respectively). Bleb needling was performed in 28.4% of cases, and 18% underwent a secondary procedure. CONCLUSIONS: The Xen 45 gel stent implant offers acceptable long-term efficacy for the treatment of open-angle glaucoma. However, there is a significant rate of reoperation and needling, and outcomes are less effective if combined with cataract surgery.

Association between obstructive coronary disease and diabetic retinopathy: Cross-sectional study of coronary angiotomography and multimodal retinal imaging.

AIMS: To investigate the association between diabetic retinopathy (DR) and coronary artery disease (CAD) using coronary angiotomography (CCTA) and multimodal retinal imaging (MMRI) with ultra-widefield retinography and optical coherence tomography angiography and structural domain. METHODS: Single-center, cross-sectional, single-blind. Patients with diabetes who had undergone CCTA underwent MMRI. Uni and multivariate analysis were used to assess the association between CAD and DR and to identify variables independently associated with DR. RESULTS: We included 171 patients, 87 CAD and 84 non-CAD. Most CAD patients were males (74 % vs 38 %, P < 0.01), insulin users (52 % vs 38 %, p < 0.01) and revascularized (64 %). They had a higher prevalence of DR (48 % vs 22 %, p = 0.01), microaneurysms (25 % vs 13 %, p = 0.04), intraretinal cysts (22 % vs 8 %, p = 0.01) and areas of reduced capillary density (46 % vs 20 %, p < 0.01). CAD patients also had lower mean vascular density (MVD) (15.7 % vs 16.5,%, p = 0.049) and foveal avascular zone (FAZ) circularity (0.64 ± 0.1 vs 0.69 ± 0.1, p = 0.04). There were significant and negative correlations between Duke coronary score and MVD (r = -0.189; p = 0.03) and FAZ circularity (r = -0,206; p = 0.02). CAD, DM duration and insulin use independently associated with DR. CONCLUSIONS: CAD patients had higher prevalence of DR and lower MVD. CAD, DM duration and insulin use were independently associated with DR.

Neointimal myofibroblasts contribute to maintaining Th1/Tc1 and Th17/Tc17 inflammation in giant cell arteritis.

Vascular smooth muscle cells (VSMCs) have been shown to play a role in the pathogenesis of giant cell arteritis (GCA) through their capacity to produce chemokines recruiting T cells and monocytes in the arterial wall and their ability to migrate and proliferate in the neointima where they acquire a myofibroblast (MF) phenotype, leading to vascular stenosis. This study aimed to investigate if MFs could also impact T-cell polarization. Confocal microscopy was used to analyze fresh fragments of temporal artery biopsies (TABs). Healthy TAB sections were cultured to obtain MFs, which were then treated or not with interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) and analyzed by immunofluorescence and RT-PCR. After peripheral blood mononuclear cells and MFs were co-cultured for seven days, T-cell polarization was analyzed by flow cytometry. In the neointima of GCA arteries, we observed a phenotypic heterogeneity among VSMCs that was consistent with a MF phenotype (α-SMA+CD90+desmin+MYH11+) with a high level of STAT1 phosphorylation. Co-culture experiments showed that MFs sustain Th1/Tc1 and Th17/Tc17 polarizations. The increased Th1 and Tc1 polarization was further enhanced following the stimulation of MFs with IFN-γ and TNF-α, which induced STAT1 phosphorylation in MFs. These findings correlated with increases in the production of IL-1ß, IL-6, IL-12 and IL-23 by MFs. Our study showed that MFs play an additional role in the pathogenesis of GCA through their ability to maintain Th17/Tc17 and Th1/Tc1 polarizations, the latter being further enhanced in case of stimulation of MF with IFN-γ and TNF-α.

Cystoid Macular Edema after Rhegmatogenous Retinal Detachment Repair with Pars Plana Vitrectomy: Rate, Risk Factors, and Outcomes.

(1) Background: The aim was to describe the rate and outcomes of cystoid macular edema (CME) after pars plana vitrectomy (PPV) for primary rhegmatogenous retinal detachment (RRD) and to identify risk factors and imaging characteristics. (2) Methods: A retrospective consecutive case study was conducted over a 5-year period among adult patients who underwent PPV for primary RRD repair. The main outcome measure was the rate of CME at 12 months following PPV. (3) Results: Overall, 493 eyes were included. The CME rate was 28% (93 patients) at 12 months. In multivariate analysis, eyes with worse presenting visual acuity (VA) (odds ratio [OR], 1.55; 95% CI, 1.07-2.25; p = 0.02) and grade C proliferative vitreoretinopathy (PVR) (OR, 2.88; 95% CI, 1.04-8.16; p = 0.04) were more at risk of developing CME 1 year after PPV. Endolaser retinopexy was associated with a greater risk of CME than cryotherapy retinopexy (OR, 3.06; 95% CI, 1.33-7.84; p = 0.01). Eyes undergoing cataract surgery within 6 months of the initial RRD repair were more likely to develop CME at 12 months (OR, 1.96; 95% CI, 1.06-3.63; p = 0.03). (4) Conclusions: CME is a common complication after PPV for primary RRD repair. Eyes with worse presenting VA, severe PVR at initial presentation, endolaser retinopexy, and cataract surgery within 6 months of initial RRD repair were risk factors for postoperative CME at 12 months.

Incidence, Risk Factors, and Outcomes of Rhegmatogenous Retinal Detachment after Intravitreal Injections of Anti-VEGF for Retinal Diseases: Data from the Fight Retinal Blindness! Registry.

PURPOSE: To report the estimated incidence, probability, risk factors, and 1-year outcomes of rhegmatogenous retinal detachment (RRD) in eyes receiving intravitreal injections (IVTs) of VEGF inhibitors for various retinal conditions in routine clinical practice. DESIGN: Retrospective analysis of data from a prospectively designed observational outcomes registry: the Fight Retinal Blindness! PARTICIPANTS: Eyes of patients starting IVTs of VEGF inhibitors (ranibizumab, aflibercept, or bevacizumab) for neovascular age-related macular degeneration, diabetic macular edema, or retinal vein occlusion from January 1, 2006, to December 31, 2020. All eyes that developed RRD within 90 days of IVTs were defined as cases with RRD and were matched with control eyes. METHODS: Estimated incidence, probability, and hazard ratios (HRs) of RRD were measured using Poisson regression, Kaplan-Meier survival curve, and Cox proportional hazards models. Locally weighted scatterplot smoothing curves were used to compare visual acuity (VA) between cases and matched controls. MAIN OUTCOME MEASURES: Estimated incidence of RRD. RESULTS: We identified 16 915 eyes of 13 792 patients who collectively received 265 781 IVTs over 14 years. Thirty-six eyes were reported to develop RRD over the study period. The estimated incidence (95% confidence interval [CI]) per year per 1000 patients and per 10 000 injections was 0.77 (0.54-1.07) and 1.36 (0.95-1.89), respectively. The probability of RRD did not significantly increase at each successive injection (P = 0.95) with the time of follow-up. Older patients (HR [95% CI] = 1.81 [1.21-3.62] for every decade increase in age, P < 0.01) were at a higher risk of RRD, whereas patients with good presenting VA (HR [95% CI] = 0.85 [0.70-0.98] for every 10-letter increase in VA, P = 0.02) were at a lower risk. Neither the type of retinal disease (P = 0.52) nor the VEGF inhibitor (P = 0.09) was significantly associated with RRD risk. Cases with RRD lost 3 lines of vision on average compared with the prior RRD VA and had significantly fewer injections than matched controls over the year after the RRD. CONCLUSIONS: Rhegmatogenous retinal detachment is a rare complication of VEGF inhibitor IVT in routine clinical practice with poor visual outcomes at 1 year.

Macular Pigment and Open-Angle Glaucoma in the Elderly: The Montrachet Population-Based Study.

(1) Background: To compare macular pigment optical density (MPOD) and its spatial distribution between eyes with primary open-angle glaucoma (POAG) and control eyes in an elderly population. (2) Methods: The Montrachet study (Maculopathy Optic Nerve and nutrition neurovAsCular and HEarT) is a population-based study including participants aged 75 years and over. All participants had a slit lamp examination, fundus photographs, and a questionnaire about their medical past history and smoking status. Optic disc spectral domain optical coherence tomography was also performed. All glaucoma-suspected patients were convocated to have a new full examination. We only retained one eye with POAG for analysis in the glaucoma group and one eye without optic neuropathy in the control participants group. MPOD measurements were performed with the two-wavelength autofluorescence method (488 and 514 nm). (3) Results: Overall, 601 eyes had MPOD measurements among 1153 participants. Among the 601 eyes, 48 had POAG. The mean age for the glaucoma and control participants was 84.01 ± 4.22 years and 81.94 ± 3.61 years, respectively (p < 0.001). In the multivariable analysis, we could not find any association between POAG and MPOD at 0.5° (p = 0.336). We found no significant difference regarding MP spatial distribution between the two groups (p = 0.408). (4) Conclusion: In this elderly population-based study, eyes with POAG and control eyes without optic neuropathy did not differ in terms of MPOD and MP spatial distribution.

Intraocular Pressure Changes After Intravitreal Fluocinolone Acetonide Implant: Results from Four European Countries.

INTRODUCTION: The 0.19 mg fluocinolone acetonide (FAc) intravitreal implant delivers a continuous intravitreal corticosteroid dose for the treatment of refractory diabetic macular oedema (DMO). The aim of this study was to assess the impact of an FAc intravitreal implant on intraocular pressure (IOP). METHODS: We retrospectively collected anonymised data on the patients' characteristics, DMO treatment, and IOP and IOP-lowering treatments before and after the FAc intravitreal implant between September 2013 and March 2020 in several European centres. RESULTS: A total of 221 eyes from 179 patients were included. The mean follow-up duration was 13.4 (± 12.5, range 2.4-33.5) months. Overall, 194 eyes (88.2%) had received an intravitreal dexamethasone injection before the FAc intravitreal implant. For 25 eyes (11.3%) there was a history of glaucoma, and 52 eyes (23.5%) had previous IOP-lowering treatment. Mean IOP before injection was 14.7 (3.4) mmHg and increased to 16.9 (3.7) mmHg 12 months after injection (P < 0.0001). During follow-up, 55 eyes (24.9%) required the addition or initiation of topical IOP-lowering medication, only one patient (0.5%) had laser trabeculoplasty and one patient (0.5%) a minimally invasive glaucoma surgery, and no patient required incisional IOP-lowering surgery. CONCLUSION: The FAc intravitreal implant led to substantial IOP elevation. This elevation was monitored most of the time with addition or initiation of topical IOP-lowering medication.

Incidence, risk factors and outcomes of submacular haemorrhage with loss of vision in neovascular age-related macular degeneration in daily clinical practice: data from the FRB! registry.

PURPOSE: The main purpose of the study was to report the estimated incidence, cumulative rate, risk factors and outcomes of submacular haemorrhage (SMH) with loss of vision in neovascular age-related macular degeneration (nAMD) receiving intravitreal injections (IVT) of vascular endothelial growth factor (VEGF) inhibitor in routine clinical practice. METHODS: Retrospective analysis of treatment-naïve eyes receiving IVTs of VEGF inhibitors (ranibizumab, aflibercept or bevacizumab) for nAMD from 1 January 2010 to 31 December 2020 that were tracked the Fight Retinal Blindness! registry. Estimated incidence, cumulative rate and hazard ratios (HR) of SMH with loss of vision during treatment were measured using the Poisson regression, Kaplan-Meier survival curves and Cox proportional hazard models. RESULTS: We identified 7642 eyes (6425 patients) with a total of 135 095 IVT over a 10-year period. One hundred five eyes developed SMH with loss of vision with a rate of 1 per 1283 injections (0.08% 95% confidence interval [95% CI] [0.06; 0.09]). The estimated incidence [95% CI] was 4.6 [3.8; 5.7] SMH with loss of vision per year per 1000 treated patients during the study. The cumulative [95% CI] rate of SMH per patient did not increase significantly with each successive injection (p = 0.947). SMH cases had a mean VA drop of around 6 lines at diagnosis, which then improved moderately to a 4-line loss at 1 year. CONCLUSIONS: Submacular haemorrhage (SMH) with loss of vision is an uncommon complication that can occur at any time in eyes treated for nAMD in routine clinical practice, with only limited recovery of vision 1 year later.

Analysis of international publication trends in artificial intelligence in ophthalmology.

PURPOSE: Artificial intelligence (AI) has entered the field of medicine, and ophthalmology is no exception. The objective of this study was to report on scientific production and publication trends, to identify journals, countries, international collaborations, and major MeSH terms involved in AI in ophthalmology research. METHODS: Scientometric methods were used to evaluate global scientific production and development trends in AI in ophthalmology using PubMed and the Web of Science Core Collection. RESULTS: A total of 1356 articles were retrieved over the period 1966-2019. The yearly growth of AI in ophthalmology publications has been 18.89% over the last ten years, indicating that AI in ophthalmology is a very attractive topic in science. Analysis of the most productive journals showed that most were specialized in computer and medical systems. No journal was found to specialize in AI in ophthalmology. The USA, China, and the UK were the three most productive countries. The study of international collaboration showed that, besides the USA, researchers tended to collaborate with peers from neighboring countries. Among the twenty most frequent MeSH terms retrieved, there were only four related to clinical topics, revealing the retina and glaucoma as the most frequently encountered subjects of interest in AI in ophthalmology. Analysis of the top ten Journal Citation Reports categories of journals and MeSH terms for articles confirmed that AI in ophthalmology research is mainly focused on engineering and computing and is mainly technical research related to computer methods. CONCLUSIONS: This study provides a broad view of the current status and trends in AI in ophthalmology research and shows that AI in ophthalmology research is an attractive topic focusing on retinal diseases and glaucoma. This study may be useful for researchers in AI in ophthalmology such as clinicians, but also for scientists to better understand this research topic, know the main actors in this field (including journals and countries), and have a general overview of this research theme.

Heamatological malignancies in giant cell arteritis: a French population-based study.

OBJECTIVES: An increased risk of haematological malignancies (HM) has been reported in GCA patients. Our study aimed to investigate the incidence and the type of HM occurring in GCA. METHODS: All patients with GCA and HM living in Côte d'Or (France) were identified by crossing data from the RHEMCO (Registre des Hémopathies Malignes de Côte d'Or) and those having a positive temporal artery biopsy between 1 January 2001 and 31 December 2018. RESULTS: Among 276 biopsy-proven GCA patients, 14 HM were identified in 12 patients (4.3%). In comparison with the general population aged >50 y, the incidence of myeloid HM and myeloproliferative syndromes were increased in GCA patients [standardized incidence ratios (SIR) = 2.71 and 5.16, respectively], with a specific increase in men with GCA (SIR = 4.82 and 9.04, respectively) but not in women. In addition, the study of SIR depending on the chronology between GCA and HM diagnoses suggests that there was an increased risk of developing GCA in men but not in women, after a diagnosis of myeloid HM (SIR = 9.56), especially if it was a MPS (SIR = 17.56). CONCLUSIONS: Our study shows a particular epidemiology of HM in GCA patients, which is characterized by an increased incidence of myeloid HM, especially MPS, in male GCA patients. The chronology of the diagnoses of GCA and HM raises the hypothesis that clonal hematopoiesis may be implicated in some cases of GCA.

Myocardial infarction during giant cell arteritis: A cohort study.

BACKGROUND: Cardiovascular risk is increased in giant cell arteritis (GCA). We aimed to characterize myocardial infarction (MI) in a GCA cohort, and to compare the GCA and non-GCA population affected by MI. METHODS: In patients with a biopsy-proven diagnosis of GCA between 1 January 2001 and 31 December 2016 in Côte D'Or (France), we identified patients with MI by crossing data from the territorial myocardial infarction registry (Observatoire des Infarctus de Côte d'Or) database. Five controls (non-GCA + MI) were paired with one case (GCA + MI) after matching for age, sex, cardiovascular risk factors and prior cardiovascular disease. MI were characterized as type 1 MI (T1MI), resulting from thrombus formation due to atherothrombotic disease, or type 2 MI (T2MI), due to a myocardial supply/demand mismatch. GCA-related MI was defined as MI occurring within 3 months of a GCA flare (before or after). RESULTS: Among 251 biopsy-proven GCA patients, 13 MI cases were identified and paired with 65 controls. MI was GCA-related in 6/13 cases, accounting for 2.4% (6/251) of our cohort. T2MI was more frequently GCA-related than GCA-unrelated (80% vs. 16.7%, p = 0.080), and GCA diagnosis was the only identified triggering factor in 75% of GCA-related T2MI. GCA-unrelated MI were more frequently T1MI and occurred in patients who had received a higher cumulative dose of prednisone (p = 0.032). GCA was not associated with poorer one-year survival. CONCLUSIONS: GCA-related MI are mainly T2MI probably caused by systemic inflammation rather than coronaritis. GCA-unrelated MI are predominantly T1MI associated with atherothrombotic coronary artery disease.

Vascular density with optical coherence tomography angiography and systemic biomarkers in low and high cardiovascular risk patients.

We aimed to compare retinal vascular density in Optical Coherence Tomography Angiography (OCT-A) between patients hospitalized for acute coronary syndrome (ACS) and control patients and to investigate correlation with angiogenesis biomarkers. Patients hospitalized for an acute coronary syndrome (ACS) in the Intensive Care Unit were included in the "high cardiovascular risk" group while patients without cardiovascular risk presenting in the Ophthalmology department were included as "control". Both groups had blood sampling and OCT-A imaging. Retina microvascularization density in the superficial capillary plexus was measured on 3 × 3 mm angiograms centered on the macula. Angiopoietin-2, TGF-ß1, osteoprotegerin, GDF-15 and ST-2 were explored with ELISA or multiplex method. Overall, 62 eyes of ACS patients and 42 eyes of controls were included. ACS patients had significantly lower inner vessel length density than control patients (p = 0.004). A ROC curve found that an inner vessel length density threshold below 20.05 mm-1 was moderately associated with ACS. Significant correlation was found between serum levels of angiopoietin-2 and osteoprotegerin, and retinal microvascularization in OCT-A (R = - 0.293, p = 0.003; R = - 0.310, p = 0.001). Lower inner vessel length density measured with OCT-A was associated with ACS event and was also correlated with higher concentrations of angiopoietin-2 and osteoprotegerin.

Development of a 1-year risk-prediction nomogram for good functional response with anti-VEGF agents in naive diabetic macular oedema.

PURPOSE: To develop a risk-prediction nomogram based on baseline variables for good functional response during the 1st year of treatment with anti-VEGF agents in naive diabetic macular oedema (DME). METHODS: This retrospective study included patients presenting naive-DME treated with anti-VEGF therapy at Dijon University Hospital (France) between 1 February 2012 and 31 March 2015 (derivation cohort). We studied baseline variables that had significant associations with a good functional response to anti-VEGF agents during the 1st year of treatment. We used a program to generate a nomogram based on a binary logistic regression predictive model. Then, this nomogram was tested on data from a separate cohort of naive-DME patients from a multicenter study involving 20 French ophthalmologic centres between January 2014 and June 2015 (validation cohort). RESULTS: Age, baseline BCVA and ellipsoid zone integrity on spectral-domain optical coherence tomography (SD-OCT) are functional prognostic factors and were used to build a nomogram. The nomogram showed excellent discrimination for good functional responders (area under the curve (AUC) = 0.906, 95% confidence interval (95% CI) = [0.849-0.964], p = 0.004). The discriminative power of this nomogram was tested on the validation cohort data, demonstrating good discrimination of good functional responders (AUC = 0.942, 95% CI = [0.898-0.986], p < 0.001). CONCLUSION: This nomogram provides a useful estimation of a good functional response in naive-DME patients treated with anti-VEGF agents.

Recurrent Exposure of XEN Gel Stent Implant and Conjunctival Erosion.

PURPOSE: The purpose of this study was to report a case of recurrent conjunctival erosion and XEN Gel Stent exposure after implantation in a primary open-angle glaucoma patient. Minimally invasive glaucoma surgery (MIGS) is a new approach in glaucoma surgery, and there is a lack of published data with regard to the management of postoperative ocular surface complications. METHODS: This is a case report of a patient with a persistent corneal erosion after XEN Gel Stent implantation. A standalone MIGS surgery was planned for both eyes in this case of refractory glaucoma. Despite a first surgical revision, the patient was suffering from a chronic leaking bleb, an exposed XEN Gel Stent, and severe hypotonia in the left eye. RESULTS: A free conjunctival autografting technique covered with a complementary amniotic membrane graft was performed under local anesthesia. One month following bleb revision, the intraocular pressure was 13 mm Hg on medical treatment, and slit-lamp examination showed a well-formed moderate bleb with no leakage. CONCLUSIONS: This is the first described case of the use of a free conjunctival autograft to treat a persistently leaking bleb after XEN Gel Stent implantation. This case highlights the potential complication of conjunctival erosion due to XEN Gel Stent implantation. It emphasizes the management of complicated filtration blebs after MIGS surgery.

Trends in operating room-based glaucoma procedures in France from 2005 to 2014: a nationwide study.

PURPOSE: To report the trends in operating room-based glaucoma procedures from 2005 to 2014 in France. METHODS: We identified operating room-based glaucoma procedures (trabeculectomies, deep sclerectomies, aqueous shunts and ciliary body destructions) performed in France from 2005 to 2014 by means of billing codes from a national database. The annual rates and incidence of these procedures per 100 000 inhabitants were analysed globally and in three age groups: 0-14 years, 15-59 years and over 60 years. RESULTS: The annual rate of trabeculectomies decreased slightly during the study period, while the rate for other surgical techniques (deep sclerectomies, aqueous drainage procedures and ciliary body destructions) increased. The overall rate of glaucoma surgeries was higher in areas with populations of African descent than in areas predominantly composed of Caucasian populations: 1.60 (95% CI 1.51 to 1.70, p<0.0001). CONCLUSIONS: Trabeculectomy was the most commonly performed operating room-based glaucoma procedure in France from 2005 to 2014. Other modalities such as deep sclerectomies, aqueous drainage procedures and ciliary body destruction gained greater acceptance among French ophthalmologists during this 10-year period.