Study protocol of OmegaROP-2 prospective study: expression of placental fatty acid receptors in preterm newborns with retinopathy of prematurity.

BACKGROUND: Incomplete vascularization of the retina in preterm infants carries a risk of retinopathy of prematurity (ROP). Progress in neonatal resuscitation in developing countries has led to the survival of an increasing number of premature infants, resulting in an increased rate of ROP and consequently in visual disability. Strategies to reduce ROP involve optimizing oxygen saturation, nutrition, and normalizing factors such as insulin-like growth factor 1 and n-3 long-chain polyunsaturated fatty acids (LC-PUFA). Our previous study, OmegaROP, showed that there is an accumulation or retention of docosahexaenoic acid (DHA) in mothers of infants developing ROP, suggesting abnormalities in the LC-PUFA placental transfer via fatty acid transporting proteins. The present study aims to better understand the LC-PUFA transport dysfunction in the fetoplacental unit during pregnancy and to find a novel target for the prevention of ROP development. METHODS: The study protocol is designed to evaluate the correlation between the expression level of placental fatty acid receptors and ROP occurrence. This ongoing study will include 100 mother-infant dyads: mother-infant dyads born before 29 weeks of gestational age (GA) and mother-infant dyads with full-term pregnancies. Recruitment is planned over a period of 46 months. Maternal and cord blood samples as well as placental tissue samples will be taken following delivery. ROP screening will be performed using wide-field camera imaging according to the International Classification of ROP consensus statement. DISCUSSION: The results of this study will have a tangible impact on public health. Indeed, if we show a correlation between the expression level of placental omega-3 receptors and the occurrence of ROP, it would be an essential step in discovering novel pathophysiological mechanisms involved in this retinopathy. TRIAL REGISTRATION: NCT04819893.

Safety and long-term efficacy of repeated dexamethasone intravitreal implants for the treatment of cystoid macular edema secondary to retinal vein occlusion with or without a switch to anti-VEGF agents: a 3-year experience.

PURPOSE: To evaluate the safety and efficacy of repeated dexamethasone intravitreal implants (DEX implants) over 3 years in eyes with macular edema (ME) secondary to branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO). METHODS: We conducted a 3-year, retrospective, multicenter study that included adult patients with ME secondary to BRVO or CRVO treated with first-line DEX implants. Patients were divided into two different subgroups: patients who received DEX implant injections only (group 1) and those who received DEX implants first and then were switched to anti-VEGF agents (group 2). Primary endpoints were changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline to month 6 and month 36. Secondary endpoints included changes in both BCVA and CRT after each DEX implant and adverse events, particularly cataract extraction and elevated intraocular pressure (IOP). RESULTS: Sixty-six patients with a median [IQR (interquartile ratio)] age of 72 [65.0; 81.1] years were included (40.9% BRVO, 59.1% CRVO), who received a median of 5.0 [min, 1.0; max, 10.0] DEX implants over 3 years. Median [IQR] time to retreatment was 4.8 [4.2; 6.0] months. The median [IQR] improvements in BCVA from baseline until months 6 and 36 were respectively + 10.0 [0; + 20.0] letters (P = 0.040) and + 10.0 [- 8.7; + 20.0] letters (P = 0.364) in the whole population. In group 1, the results were similar, whereas in group 2, BCVA significantly increased at M36 compared with baseline (P = 0.003). The median [IQR] CRT reductions from baseline to months 6 and 36 were respectively - 227.5 [- 337.0; - 52.7] µm and - 224.0 [- 405.0; - 83.8] µm (P < 0.001) in the whole population. Results were similar in both groups. The most common adverse events were cataract extraction (70.4%) and elevated IOP (54.5%). No other serious local complications were observed. Treatment was switched to anti-VEGF agents in 16 (24.2%) patients. CONCLUSIONS: DEX implants are an effective treatment for BRVO and CRVO-associated ME over 3 years. It is a valid treatment even though complications remain frequent. However, functional efficacy seems to decrease with time and repeated injections.

Effects of topical docosahexaenoic acid on postoperative fibrosis in an animal model of glaucoma filtration surgery.

PURPOSE: The aim of this study was to evaluate docosahexaenoic acid (DHA) as a potential antifibrotic agent after glaucoma filtration surgery (GFS) in rats. METHODS: A total of 36 10-week-old Brown Norway rats underwent GFS. Animals were equally divided into three groups: a control group, a DHA group and a mitomycin C (MMC) group. Intraocular pressure (IOP) was measured using a dynamic rebound tonometer, and a photograph of the surgical site was taken on days 1, 3, 7, 10, 14 and 17. The incorporation of DHA into fibroblasts was evaluated by gas chromatography. The expression of alfa-smooth muscle actin (α-SMA) and Smad proteins was assessed by Western blotting. RESULTS: IOP decreased after surgery in animals from the three groups on day 1 after surgery. Over time, IOP remained lower in the DHA and MMC groups than in the control group (median [interquartile range] 8.0 [7.0-8.0] and 8.0 [7.3-8.0] mmHg vs. 9.0 [8.0-9.0] mmHg, respectively; p < 0.001). Bleb area in the DHA and MMC groups remained larger than that of the control group from day 7 to day 14 (3.9 [2.9-5.2] and 3.5 [2.3-4.4] mm2 vs. 2.3 [2.0-2.8] mm2 , respectively; p = 0.0021). We did not observe any change in DHA concentrations in the fibroblasts of the DHA group compared with the other groups. CONCLUSION: The impact of DHA on IOP and bleb area was similar to that of MMC. The mechanisms of action of DHA in rat eye fibroblasts deserve further investigation.

Bilateral acute macular neuroretinopathy in a young woman after the first dose of Oxford-AstraZeneca COVID-19 vaccine.

PURPOSE: To report a case of bilateral acute macular neuroretinopathy following the first dose of Oxford-AstraZeneca COVID-19 (coronavirus disease 2019) vaccine in a young, Caucasian, and healthy woman. OBSERVATIONS: A 25-year-old Caucasian female patient presented to the ophthalmology department of Dijon University Hospital with a 3-week history of black spots and paracentral scotoma in both eyes. She had no past medical history and was using the combined estrogen-progestin oral contraceptive (COC). These symptoms occurred 24 h after receiving the first Oxford-AstraZeneca COVID-19 vaccination dose. The ophthalmologic signs were preceded a few hours earlier by fever and flu-like symptoms. Ophthalmologic examination revealed a preserved visual acuity with a quiet anterior segment and normal fundus in both eyes. Findings on multimodal retinal imaging, particularly near-infrared reflectance (NIR) and optical coherence tomography (OCT) imaging, were classical of an acute macular neuroretinopathy in both eyes. CONCLUSIONS AND IMPORTANCE: COVID-19 vaccination is justified as an essential public health measure. Acute macular neuroretinopathy may occur in patient receiving a COVID-19 vaccination dose. Further reports are needed to confirm this association. Physicians should be aware of this complication and request an eye examination with at least OCT or NIR imaging in the case of any visual symptoms after vaccination, notably in young women using COC.

Association between Obstetric Complications and Intravitreal Anti-Vascular Endothelial Growth Factor Agents or Intravitreal Corticosteroids.

This nationwide population-based cohort study aimed to describe the use of intravitreal injections (IVTs) of anti-vascular endothelial growth factor (anti-VEGF) agents and corticosteroids in pregnant women in France and to report on the incidence of obstetric and neonatal complications. All pregnant women in France who received any anti-VEGF or corticosteroid IVT during pregnancy or in the month preceding pregnancy from 1 January 2009 to 31 December 2018 were identified in the national medico-administrative databases. Between 2009 and 2018, there were 5,672,921 IVTs performed in France. Among these IVTs, 228 anti-VEGF or corticosteroid IVTs were administered to 139 women during their pregnancy or in the month preceding their pregnancy. Spontaneous abortion or the medical termination of pregnancy occurred in 10 women (16.1%) who received anti-VEGF agents and in one (3.1%) of the women who received corticosteroids (p = 0.09). This is the first national cohort study of pregnant women treated with anti-VEGF or corticosteroid IVTs. We found a high incidence of obstetric complications in pregnant women treated with anti-VEGF or corticosteroid IVTs but could not demonstrate a statistically significant association between the intravitreal agents and these complications. These agents should continue to be used with great caution in pregnant women.

Mobile Telemedicine Screening for Diabetic Retinopathy Using Nonmydriatic Fundus Photographs in Burgundy: 11 Years of Results.

We analyzed the results of mobile screening for diabetic retinopathy (DR) using retinal photographs, comparing these results between rural and periurban areas, and before and after the first national COVID-19 pandemic lockdown. The Burgundy Union Régionale des Professionnels de Santé (URPS) has organized an annual DR screening since 2004. The examination, performed by an orthoptist, consisted of taking the patient's history, intraocular pressure measurement, and taking retinal photographs. After remote transmission, the examinations were interpreted by participating ophthalmologists at the Dijon University Hospital. In September 2016, the screening was open to periurban townships. In 11 years, 10,220 patients were screened: 1420 patients (13.9%) had DR of any type, with an average age of 68.5 (±11.3) years, and 59.2% were men. These patients had a statistically significantly higher glycated hemoglobin level (7.4% vs. 7.0%) and a longer duration of diabetes (13.8 vs. 9.3 years) than patients without DR. When comparing rural and periurban areas and periods before and after the beginning of the COVID-19 pandemic, we did not find any significant difference in the screening results. The results of this study are in line with the average findings of similar studies comparing screening strategies for DR. The early detection of DR can benefit from mobile telemedicine screening, identifying a considerable number of patients at an elevated risk, especially in rural areas where access to ophthalmological care is limited.

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.

Subretinal Drusenoid Deposits in the Elderly in a Population-Based Study (the Montrachet Study).

Purpose: The aim of this study was to investigate the prevalence of subretinal drusenoid deposits (SDD) and to identify associated factors in an elderly population. Methods: The participants of the population-based Montrachet study underwent an exhaustive ophthalmologic examination, including color fundus photography and macular spectral domain-optical coherence tomography (SD-OCT), coupled with infrared reflectance imaging. The presence of SDD and other age-related macular degeneration lesions, according to the European Eye Epidemiology SD-OCT classification of macular diseases, and subfoveal choroidal thickness were recorded. Moreover, the association of SDD and both clinical and demographic factors as well as plasma levels of vitamin E and lutein/zeaxanthin (L/Z) were analyzed. Results: The mean age of patients was 82.3 ± 3.8 years and 62.7% were female. The prevalence of SDD was 18.1% (n = 205) in the subjects with at least one eye interpretable (n = 1135). In multivariate analysis, SDD was positively associated with increasing age (OR, 4.6; 95% CI, 2.8-7.7; P < 0.001 for subjects aged >85 years), female sex (OR, 1.7; 95% CI, 1.2-2.4; P = 0.005), and plasma L/Z level (OR, 1.2; 95% CI, 1.0-1.5; P = 0.039), and negatively associated with lipid-lowering drugs use (OR, 0.5; 95% CI, 0.3-0.9; P = 0.014 for statin medications) and subfoveal choroidal thickness (OR, 0.8; 95% CI, 0.7-0.9; P = 0.002). Conclusions: The prevalence of SDD was high in subjects older than 75 years, more frequent in women, and was associated with a thinner choroid. The association with lipid-lowering drugs deserves further investigation.

Retinal Vascular Density as A Novel Biomarker of Acute Renal Injury after Acute Coronary Syndrome.

Iodinated contrast agent (ICA)-induced acute kidney injury (AKI) following acute coronary syndrome (ACS) is a frequent complication, which may lead to chronic kidney disease and increased mortality. Optical coherence tomography angiography (OCT-A) of the retina is new tool delivering a rapid and noninvasive assessment of systemic microvascularization, which is potentially involved in the occurrence of ICA-induced AKI. Between October 2016 and March 2017, 452 ACS patients were admitted to our cardiac intensive care unit. OCT-A was performed within 48 h after the ICA injection. Patients with a history of retinal disease were excluded. The patients included were divided into two groups depending on whether or not AKI occurred after injection of ICA, according to KDIGO criteria. Of the 216 patients included, 21 (10%) presented AKI. AKI was significantly associated with age, Mehran score, GRACE score, and NT-proBNP. AKI patients had significantly lower retinal vascular density (RVD)) and had more frequent low RVD (81% vs 45%, P = 0.002). Adding low RVD to the Mehran score and the NT-proBNP, or to the GRACE score and the NT-proBNP, significantly improved their predictive values, suggesting that systemic microvascular involvement remains incompletely addressed by either standard risk scores or factors known to be associated with ICA-induced AKI.

Subfoveal Choroidal Thickness, Cardiovascular History, and Risk Factors in the Elderly: The Montrachet Study.

Purpose: To measure subfoveal choroidal thickness (SFCT) in the elderly and to determine the associations among SFCT, cardiovascular history, and the 10-year risk of fatal cardiovascular disease (CVD). Methods: We conducted a population-based study, the Montrachet (Maculopathy Optic Nerve, nuTRition neurovAsCular, and HEarT disease) study, in subjects older than 75 years. SFCT was measured with spectral-domain optical coherence tomography (SD-OCT) with enhanced-depth mode imaging. Participants underwent a comprehensive eye examination. The history of CVD, CVD risk factors, and a score-based estimation of their 10-year risk of cardiovascular mortality (Heart Score) were collected. Results: Overall, 764 participants were retained for analysis. The mean SFCT was 206.4 ± 83.0 µm. The mean age was 81.9 ± 3.6 years. After a multivariable analysis, older age (ß = -32.56 µm, P < 0.001) and longer axial length (ß = -20.71 µm, P < 0.001) were independently associated with thinner SFCT. SFCT was not significantly associated with sex, cardiovascular history, classical CVD risk factors, or prognostic risk score. Conclusions: This study confirms that longer axial length and older age are associated with thinner SFCT. However, SFCT does not appear to be a biomarker for cardiovascular history in this study.

Preoperative Prognostic Factors and Predictive Score in Patients Operated On for Combined Cataract and Idiopathic Epiretinal Membrane.

PURPOSE: To report preoperative prognostic factors associated with visual acuity recovery 1 year after combined cataract and idiopathic epiretinal membrane (ERM) surgery and to introduce a predictive score. DESIGN: Interventional case series and estimation of a predictive score. METHODS: One hundred forty-two patients (1 eye per patient) operated on for combined cataract and idiopathic ERM in the University Hospital of Dijon were followed for 12 months. Preoperative clinical features and spectral-domain optical coherence tomography (OCT) parameters were compared between eyes that recovered ≥20/20 final best-corrected visual acuity (BCVA) and those with <20/20 final BCVA. Multivariate analysis and predictive score were provided. RESULTS: At 12 months, 60 eyes (42%) recovered ≥20/20 BCVA and 82 (58%) had lower visual results. Logistic regression analysis showed that final BCVA was associated with age (P = .040), duration of symptoms (P = .025), initial BCVA (P = .002), and inner and outer segment (IS/OS) junction disruption on spectral-domain OCT (P = .010). The preoperative 10-point predictive score including these parameters reached 82% sensitivity and 66% specificity. With a score >5, patients had a ≥56% chance of recovering 20/20 final BCVA instead of ≤27% when the score was ≤5. CONCLUSIONS: Age, duration of symptoms, and initial BCVA appear to be reliable prognostic factors in patients undergoing combined cataract and idiopathic ERM surgery. Combining these factors with analysis of the IS/OS junction provides a predictive score to estimate individual chances of good visual outcome.

Measurement of adherence to brimonidine therapy for glaucoma using electronic monitoring.

PURPOSE: To assess the patient adherence and behavior with brimonidine twice daily (bid) or 3 times daily (tid) in patients used to topical glaucoma medication. PATIENTS AND METHODS: Seventy-five patients with glaucoma or ocular hypertension were enrolled in a prospective, observational cohort study. Consenting patients were randomly assigned to brimonidine bid or tid and received conventional brimonidine eye drops with attached electronic monitoring devices for 4 weeks. Patients were not explicitly informed on the compliance monitoring. RESULTS: The study was completed by 67 patients (89%). In 65 patients (97%), at least 1 dosing interval exceeded 24 hours. The mean adherence rates were better in the brimonidine bid group (72 ± 19% vs. 62 ± 16%, P=0.04), although dosing frequency was higher in the tid group (1.9 ± 0.5 vs. 1.4 ± 0.4 per day; P<0.001). On average medication coverage was 70% for the bid group and 67% for the tid group; 19 patients (28%) had a coverage rate above 75%, 42 patients (63%) 50% to 75%, and 6 (9%) below 50%. Patients with normal-tension glaucoma had lower coverage rates than patients with primary open-angle glaucoma and ocular hypertension (P<0.05). Data also showed that on average 20% of the glaucoma medication was wasted owing to inefficient drug delivery by using more than 1 drop per dosing. CONCLUSIONS: Individual adherence with brimonidine was highly variable and pharmacologically insufficient for more than two-third of the patients. Special attention should be paid to compliance of patients with normal-tension glaucoma. Our findings underline the need to improve individual adherence and drug delivery in topical glaucoma therapy.