Incidence of macular displacement after rhegmatogenous retinal detachment surgery using ultra-widefield fundus autofluorescence.

PURPOSE: The incidence of retinal displacement after rhegmatogenous retinal detachment (RRD) surgery is variable and its clinical consequences are unclear. The aim of this study was to assess the incidence and clinical features of retinal displacement after RRD surgery by using ultra-widefield (UWF) imaging. METHODS: Retrospective observational study including all consecutive patients who underwent RRD surgery at the Rothschild Foundation Hospital. Postoperative data included the visual acuity and symptoms of visual impairment. Macular retinal displacement occurrence and its features were assessed and measured by using the autofluorescence images. RESULTS: A total of 123 eyes were included. UWF fundus autofluorescence revealed the presence of macular retinal displacement in 14 (11%) eyes. All displacements were inferior, with a mean angle of 3.8°. Patients with and without macular displacement did not differ in postoperative visual acuity. The retinal detachment extent and preoperative macular involvement were not significantly associated with the occurrence of retinal displacement. CONCLUSION: In this representative cohort of eyes that underwent RRD surgery with systematic screening for postoperative retinal displacement by UWF fundus autofluorescence, 11% of eyes experienced an inferior retinal shift. As in other cohorts, the presence of metamorphopsia was not associated with the occurrence of retinal shift.

Effectiveness and safety of cataract surgery in laminar air flow device versus traditional scrubs: A 1-year non-inferiority pilot study.

Purpose: The study aimed to assess the safety and the non-inferiority of cataract surgery outside an operating room using the Surgicube®, a mobile laminar airflow (LAF) device. Settings: This single-center study was conducted at the Rothschild Foundation, Paris, France. Design: This is a retrospective cross-sectional study. Methods: All patients operated on for cataracts using the Surgicube® between February 2020 and February 2021 were included and controlled by a cohort of patients operated on for cataracts in the traditional theater during the same period. Patients with a postoperative follow-up of less than 1 month were excluded. Data collection was carried out using the patient's medical record. The primary endpoint was the evaluation of the number of endophthalmitis in the two groups. The secondary judgment criteria were the analysis of the various complications and the Logmar visual acuity at 1 month in the two groups. All the patients underwent an OCT retinal examination. Results: A total of 923 randomized patients who underwent cataract surgery between 2020 and 2021 have been included in the study. Among them, 448 patients were operated on using the Surgicube, and 475 patients underwent surgery in the traditional operating room using the same lens phacoemulsification technique. There are no significant differences between the two groups (p > 0.05). Conclusion: Cataract surgery using the Surgicube® outside a conventional operating room seems non-inferior to conventional scrub.

Prospective longitudinal study on prognostic factors of visual recovery and structural change after a first episode of optic neuritis.

BACKGROUND AND PURPOSE: This study was undertaken to determine the role of optical coherence tomography (OCT) in predicting the final visual and structural outcome, and to evaluate the correlation between functional eye outcome and retinal changes, in patients with a first episode of optic neuritis (ON). METHODS: In this prospective study, consecutive adult patients with acute ON underwent ophthalmological evaluation at baseline and at 1 and 12 months, including OCT measurements of peripapillary retinal nerve fiber layer (pRNFL), macular ganglion cell and inner plexiform layer, and inner nuclear layer thicknesses; high- and low-contrast visual acuity; visual field assessment; and baseline brain magnetic resonance imaging. Univariate and multivariate linear regressions were used to assess predictive factors of outcome. Correlations between 12-month visual function and retinal structure were estimated by Spearman coefficients. Two groups of patients were analyzed, with or without multiple sclerosis (MS). RESULTS: Among 116 patients, 79 (68.1%) had MS, and 37 (31.9%) had ON not related to MS (including 19 idiopathic [i.e., isolated] ON, and 13 and five with myelin oligodendrocyte glycoprotein and aquaporin-4 antibodies, respectively). We found no independent predictive factor of visual and retinal outcome. Analysis of the relationship between the visual field test (mean deviation) and pRNFL thickness demonstrated a threshold of 75.4 µm and 66.4 µm, below which the mean deviation was worse, for patients with MS (p = 0.007) and without MS (p < 0.001), respectively. CONCLUSIONS: We found that inner retinal layer measurements during the first month are not predictive of final outcome. The critical threshold of axonal integrity, below which visual function is damaged, is different between patients with and without MS.

Activity of Systemic Treatments After Cabozantinib Failure in Advanced Metastatic Renal Cell Carcinoma.

BACKGROUND: Cabozantinib, a potent multityrosine kinases inhibitor (TKI), has demonstrated overall survival (OS) benefit over everolimus in patients previously treated with VEGFR TKI for metastatic Renal Cell Carcinoma (mRCC). The efficacy of systemic treatments after cabozantinib failure has not been investigated. MATERIALS AND METHODS: We conducted a retrospective study on patients receiving systemic treatment after cabozantinib failure in heavily pretreated patient with mRCC. We assessed Time to Treatment Failure (TTF), OS and objective response rate (ORR). RESULTS: Among 150 patients treated with cabozantinib in our institution, 56 (37.3%) received subsequent systemic therapy and were eligible for the analysis. IMDC prognostic group was good, intermediate and poor in 11 (19.6%), 24 (42.9%) and 11 (19.6%) patients, respectively. Cabozantinib was administered mainly as a second (41.1%), or third (33.9%) line treatment. axitinib or immune-checkpoint inhibitors were the subsequent treatment in 18 (34.8%) patients for each everolimus (n:16, 28.6%), other angiogenesis inhibitors (n:4, 7.1%) TTF and OS from subsequent systemic therapy after cabozantinib failure were 2.8 months (95%CI 1.9-3.7) and 7.7 months (95%CI 4.4-10.8), respectively. ORR was 8.7% and 2 patients with axitinib and 2 patients treated with Immune checkpoint inhibitors achieved a partial response. CONCLUSION: Overall, activity of systemic therapies after cabozantinib was limited.

Evaluation of a uniplanar pupil expansion ring in small-pupil cataract surgery: a feasibility study.

PURPOSE: The aim of this study was to evaluate the effectiveness of a disposable uniplanar pupil expansion device in small-pupil cataract surgery. METHODS: This is a feasibility study carried out at the Rothschild Foundation, Paris, France. Patients undergoing routine cataract surgery with a dilated pupil size < 6 mm, and who agreed to participate in the study were included. The trial enrolled 25 patients, of whom 21 proceeded to cataract surgery using the pupil expansion device to be evaluated. The pupil diameter was measured at defined stages during the cataract surgery, which was performed by a single surgeon, in a single center setting. The 1st generation Bhattacharjee pupil expansion ring was used if the preoperative pupil size was < 6 mm. Intraoperative and postoperative adverse events were recorded. RESULTS: Pupil size immediately after the Bhattacharjee ring implantation was ≥ 6 mm for 15 eyes (71.4%). The mean dilated pupil size before ring insertion was 4.5 ± 0.8 mm (range 2.5-5.8 mm), and the mean pupil size after ring insertion was 6.1 ± 0.3 mm (range 5.9-6.8 mm). Mean pupil size following removal of the ring was 4.2 ± 0.8 mm (range 2.5-5.4 mm). Two adverse events occurred during the surgeries: 1 Bhattacharjee ring broke prior to implantation, and 1 implanted Bhattacharjee ring was unstable and removed before the end of the surgery. No postoperative adverse event was recorded. CONCLUSIONS: The Bhattacharjee ring is an effective pupil expansion device, which facilitates stable pupil expansion during cataract surgery. This study was registered as a clinical trial at clinicaltrials.gov under the number NCT02434588.

Did the COVID-19 Pandemic Increase the Incidence of Acute Macular Neuroretinopathy?

BACKGROUND: Acute macular neuroretinopathy (AMN) is an increasingly diagnosed disorder associated with several diseases. The aim of this study was to report the incidence of AMN cases diagnosed during the 2020 coronavirus disease 2019 (COVID-19) pandemic year in a French hospital, and to describe their different forms. METHODS: All patients diagnosed between 2019 and 2020, in Paris Rothschild Foundation Hospital, with AMN, paracentral acute middle maculopathy (PAMM) and multiple evanescent white dot syndrome (MEWDS) were retrospectively collected using the software Ophtalmoquery® (Corilus, V1.86.0018, 9050 Gand, Belgium). Systemic and ophthalmological data from AMN patients were analyzed. RESULTS: Eleven patients were diagnosed with AMN in 2020 vs. only one patient reported in 2019. The incidence of AMN significantly increased from 0.66/100,000 visits in 2019 to 8.97/100,000 visits in 2020 (p = 0.001), whereas the incidence of PAMM and MEWDS remained unchanged. Four (36%) of these AMN patients were tested for COVID-19 and received positive polymerase chain reaction (PCR) tests. CONCLUSIONS: The incidence of AMN cases increased significantly in our institution in 2020, which was the year of the COVID-19 pandemic. All AMN-tested patients received a positive COVID PCR test, suggesting a possible causative link. According to the different clinical presentations, AMN may reflect different severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pathogenic mechanisms.

Molecular Landscape of Therapy-related Myeloid Neoplasms in Patients Previously Treated for Gynecologic and Breast Cancers.

Definition of therapy-related myeloid neoplasms (TRMN) is only based on clinical history of exposure to leukemogenic therapy. No specific molecular classification combining therapy-related acute myeloid leukemia and therapy-related myelodysplastic syndromes has been proposed. We aimed to describe the molecular landscape of TRMN at diagnosis, among 77 patients with previous gynecologic and breast cancer with a dedicated next-generation sequencing panel covering 74 genes. We investigated the impact of clonal hematopoiesis of indeterminate potential-associated mutations (CHIP-AMs defined as presence at TRMN stage of mutations described in CHIP with a frequency >1%) on overall survival (OS) and the clinical relevance of a modified genetic ontogeny-based classifier that categorized patients in 3 subgroups. The most frequently mutated genes were TP53 (31%), DNMT3A (19%), IDH1/2 (13%), NRAS (13%), TET2 (12%), NPM1 (10%), PPM1D (9%), and PTPN11 (9%). CHIP-AMs were detected in 66% of TRMN patients, with no impact on OS. Yet, patients with CHIP-AM were older and had a longer time interval between solid tumor diagnosis and TRMN. According to our modified ontogeny-based classifier, we observed that the patients with TP53 or PPM1D mutations had more treatment lines and complex karyotypes, the "MDS-like" patients were older with more gene mutations, while patients with "De novo/pan-AML" mutations were younger with more balanced chromosomal translocations. Median OS within each subgroup was 7.5, 14.5, and 25.2 months, respectively, with statistically significant difference in multivariate analysis. These results support the integration of cytogenetic and molecular markers into the future TRMN classification to reflect the biological diversity of TRMN and its impact on outcomes.

Study of choroidal thickness variations after ingestion of a taurine and caffeine-containing energy drink.

BACKGROUND & AIMS: Choroidal thickness can undergo considerable variations in response to different substances. The aim of this study was to assess the change in choroidal thickness after the ingestion of taurine and caffeine contained in the Red Bull energy drink. METHODS: Enhanced Depth Imaging - Spectral Domain Optical Coherence Tomography was used to measure subfoveal choroidal thickness (SFCT) variations in healthy volunteers at several time points after drinking a Red Bull can (25 cl). RESULTS: Forty eyes of 20 volunteers were enrolled. A significant reduction in SFCT (-14 µm, p < 0.0001) occurred at 1 h after the Red Bull intake, and was even more important (-20.14 µm, p < 0.0001) in eyes with particularly thick choroids (≥ 395 µm). SFCT measurements at 4 h were comparable to baseline. CONCLUSIONS: A concomitant ingestion of caffeine and taurine can induce a transient choroidal thinning that is more marked in eyes with thick choroids. REGISTRATION NUMBER OF CLINICAL TRIAL: NCT02856256.

Retinal and choroidal blood flow variations after an endurance exercise: A real-life pilot study at the Paris Marathon.

OBJECTIVES: To collect information about the retinal blood flow variations and other choroidal and retinal parameters during a prolonged effort such as marathon running. DESIGN: Non-randomized prospective cohort study. METHODS: Patients were recruited through an information campaign at the Rothschild Foundation Hospital (Paris, France). A first visit (V1) was planned in the month before the marathon. All participants underwent blood pressure measurement, fundus photography, spectral domain-optical coherence tomography (SD-OCT) and OCT-angiography (OCT-A). A second visit (V2) was scheduled within one hour of crossing the finish line. The same tests were repeated, using the same equipment. RESULTS: Of the 31 runners who were included, 29 finished the marathon and attended V2. At baseline, various ophthalmological abnormalities were found in 45.2% of the 58 eyes, among which almost a third concerned the optic nerve and a quarter the pachychoroid spectrum. A significant decrease in retinal vascular plexus density was found between V1 and V2 (p<0.01). While median macular and retinal nerve fiber layer (RNFL) thicknesses significantly increased after the marathon (p<0.01), median choroidal thickness significantly decreased (p<0.01). Both systolic and diastolic blood pressures significantly decreased (p<0.01 and p=0.021 respectively). CONCLUSIONS: Prolonged physical effort impacts the structure and vascularization of the retina and the choroid. Hypoxia and dehydration due to such an effort may induce a low ocular blood flow rate resulting in a choroidal thinning, contrasting with a transient subclinical ischemic edema of the inner retina and optic nerve head. CLINICAL TRIAL REGISTRATION NUMBER: NCT03864380.

Systematic Screening of COVID-19 Disease Based on Chest CT and RT-PCR for Cancer Patients Undergoing Radiation Therapy in a Coronavirus French Hotspot.

PURPOSE: Patients with cancer are presumed to be more vulnerable to COVID-19. We evaluated a screening strategy combining chest computed tomography (CT) and reverse-transcription polymerase chain reaction (RT-PCR) for patients treated with radiation therapy at our cancer center located in a COVID-19 French hotspot during the first wave of the pandemic. METHODS AND MATERIALS: Chest CT images were proposed during radiation therapy CT simulation. Images were reviewed by an expert radiologist according to the COVID-19 Reporting and Data System classification. Nasal swabs with RT-PCR assay were initially proposed in cases of suspicious imaging or clinical context and were eventually integrated into the systematic screening. A dedicated radiation therapy workflow was proposed for COVID-19 patients to limit the risk of contamination. RESULTS: From March 18, 2020 to May 1, 2020, 480 patients were screened by chest CT, and 313 patients had both chest CT and RT-PCR (65%). The cumulative incidence of COVID-19 was 5.4% (95% confidence interval [CI], 3.6-7.8; 26 of 480 patients). Diagnosis of COVID-19 was made before radiation therapy for 22 patients (84.6%) and during RT for 4 patients (15.3%). Chest CT directly aided the diagnosis of 7 cases in which the initial RT-PCR was negative or not feasible, out of a total of 480 patients (1.5%) and 517 chest CT acquisitions. Four patients with COVID-19 at the time of the chest CT screening had a false negative CT. Sensitivity and specificity of chest CT screening in patients with both RT-PCR and chest CT testing were estimated at 0.82 (95% CI, 0.60-0.95) and 0.98 (95% CI, 0.96-0.99), respectively. Adaptation of the radiation therapy treatment was made for all patients, with 7 postponed treatments (median: 5 days; interquartile range, 1.5-14.8). CONCLUSIONS: The benefit of systematic use of chest CT screening during CT simulation for patients undergoing radiation therapy during the COVID-19 pandemic seemed limited.

Prospective Multicenter Study Validate a Prediction Model for Surgery Uptake Among Women with Atypical Breast Lesions.

BACKGROUND: Diagnosis of atypical breast lesions (ABLs) leads to unnecessary surgery in 75-90% of women. We have previously developed a model including age, complete radiological target excision after biopsy, and focus size that predicts the probability of cancer at surgery. The present study aimed to validate this model in a prospective multicenter setting. - METHODS: Women with a recently diagnosed ABL on image-guided biopsy were recruited in 18 centers, before wire-guided localized excisional lumpectomy. Primary outcome was the negative predictive value (NPV) of the model. RESULTS: The NOMAT model could be used in 287 of the 300 patients included (195 with ADH). At surgery, 12 invasive (all grade 1), and 43 in situ carcinomas were identified (all ABL: 55/287, 19%; ADH only: 49/195, 25%). The area under the receiving operating characteristics curve of the model was 0.64 (95% CI 0.58-0.69) for all ABL, and 0.63 for ADH only (95% CI 0.56-0.70). For the pre-specified threshold of 20% predicted probability of cancer, NPV was 82% (77-87%) for all ABL, and 77% (95% CI 71-83%) for patients with ADH. At a 10% threshold, NPV was 89% (84-94%) for all ABL, and 85% (95% CI 78--92%) for the ADH. At this threshold, 58% of the whole ABL population (and 54% of ADH patients) could have avoided surgery with only 2 missed invasive cancers. CONCLUSION: The NOMAT model could be useful to avoid unnecessary surgery among women with ABL, including for patients with ADH. CLINICAL TRIAL REGISTRATION: NCT02523612.

Association Between Genotype and Phenotype in Consecutive Unrelated Individuals With Retinoblastoma.

Importance: Retinoblastoma (RB) is the most common pediatric intraocular neoplasm. RB is a complex model in which atypical pathogenic variants, modifier genes, imprinting, and mosaicism are known to be associated with the phenotype. In-depth understanding of RB therefore requires large genotype-phenotype studies. Objective: To assess the association between genotype and phenotype in patients with RB. Design, Setting, and Participants: This single-center, retrospective cohort study, conducted from January 1, 2000, to September 30, 2017, enrolled 1404 consecutive ascertained patients with RB who consulted an oncogeneticist. All patients had their genotype and phenotype recorded. Statistical analysis was performed from July 1, 2018, to December 31, 2018. Main Outcomes and Measures: RB1 germline and somatic pathogenic variant types, family history, and disease presentation characteristics (ie, age at diagnosis, sex, laterality, and International Intraocular Retinoblastoma Classification group). Results: Among 1404 patients with RB (734 [52.3%] female; mean [SD] age, 20.2 [21.2] months), 866 cases (61.7%) were unilateral and 538 cases (38.3%) were bilateral. Loss of function variants were found throughout the coding sequence, with 259 of 272 (95.2%) somatic pathogenic variants and 537 of 606 (88.6%) germline pathogenic variants (difference, 6.6%; 95% CI, 4.0%-9.2%; P < .001) after excluding tumor-specific pathogenic variants (ie, promoter methylation and loss of heterozygosity); a novel low-penetrance region was identified in exon 24. Compared with germline pathogenic variants estimated to retain RB protein expression, germline pathogenic variants estimated to abrogate RB protein expression were associated with an earlier mean (SD) age at diagnosis (12.3 [11.3] months among 457 patients vs 16.3 [13.2] months among 55 patients; difference, 4 months; 95% CI, 1.9-6.1 months; P = .01), more frequent bilateral involvement (84.2% among 452 patients vs 65.2% among 45 patients; difference, 18.9%; 95% CI, 14.5%-23.3%; P < .001), and more advanced International Intraocular Retinoblastoma Classification group (85.3% among 339 patients vs 73.9% among 34 patients; difference: 11.4%; 95% CI, 6.5%-16.3%; P = .047). Among the 765 nongermline carriers of an RB1 pathogenic variant, most were female (419 females [54.8%] vs 346 males [45.2%]; P = .008), and males were more likely to have bilateral RB (23 males [71.4%] vs 12 females [34.3%]; P = .01). Conclusions and Relevance: These results suggest that RB risk is associated with the germline pathogenic variant and with maintenance of RB protein and that there is a sex-linked mechanism for nongermline carriers.

Origin of transparency in scattering biomimetic collagen materials.

Living tissues, heterogeneous at the microscale, usually scatter light. Strong scattering is responsible for the whiteness of bones, teeth, and brain and is known to limit severely the performances of biomedical optical imaging. Transparency is also found within collagen-based extracellular tissues such as decalcified ivory, fish scales, or cornea. However, its physical origin is still poorly understood. Here, we unveil the presence of a gap of transparency in scattering fibrillar collagen matrices within a narrow range of concentration in the phase diagram. This precholesteric phase presents a three-dimensional (3D) orientational order biomimetic of that in natural tissues. By quantitatively studying the relation between the 3D fibrillar network and the optical and mechanical properties of the macroscopic matrices, we show that transparency results from structural partial order inhibiting light scattering, while preserving mechanical stability, stiffness, and nonlinearity. The striking similarities between synthetic and natural materials provide insights for better understanding the occurring transparency.

Association of Partial Chromosome 3 Deletion in Uveal Melanomas With Metastasis-Free Survival.

Importance: Studies on uveal melanomas (UMs) have demonstrated the prognostic value of 8q gain and monosomy 3, but the prognosis of UMs with partial deletion of chromosome 3 remains to be defined. Objective: To examine the association of partial chromosome 3 deletion in UMs with metastasis-free survival. Design, Setting, and Participants: This retrospective cohort study of 1088 consecutive comparative genomic hybridization arrays performed from May 1, 2006, to July 31, 2015, assessed patients presenting with UMs with and without partial loss of chromosome 3 at a referral center. Data analysis was performed from September 1, 2017, to November 30, 2017. Exposure: Uveal melanoma with or without partial loss of chromosome 3. Main Outcomes and Measures: Metastasis-free survival and overall survival at 60 months. Results: Of the 1088 consecutive comparative genomic hybridization arrays that were performed, 43 UMs (4.0%) in 43 patients (median age, 58 years [range, 12-79 years]; 22 [51%] female) carried partial deletions of chromosome 3. Median follow-up was 66 months (range, 1.2-126.2 months). Metastasis-free survival at 60 months was 33.6% (95% CI, 15.8%-71.4%) for UMs that carried a deletion of the BAP1 (BRCA1 associated protein 1) locus (BAP1del; 24 tumors) and 80.5% (95% CI, 64.8%-100%) for UMs without the loss of the BAP1 locus (BAP1 normal [BAP1nl]; 19 tumors) (log-rank P = .001). Overall survival at 60 months was 64.5% (95% CI, 43.5%-95.8%) in the BAP1del group vs 84.1% (95% CI, 69.0%-100%) in the BAP1nl group (log-rank P < .001). In these 43 cases, metastasis-free survival at 60 months was 100% for UMs without loss of the BAP1 locus or 8q gain, 70.0% (95% CI, 50.5%-96.9%) for UMs that carried 1 of these alterations, and 12.5% (95% CI, 2.1%-73.7%) for those that carried both (log-rank P < .001). Similarly, overall survival at 60 months was 100% for UMs without loss of the BAP1 locus or 8q gain, 80.8% (95% CI, 63.3%-100%) for UMs that carried 1 of these alterations, and 46.7% (95% CI, 23.3%-93.6%) for those that carried both (log-rank P < .001). Conclusions and Relevance: These findings suggest that partial deletion of chromosome 3 encompassing the BAP1 locus is associated with poor prognosis. A cytogenetic classification of UMs could be proposed based on the status of the BAP1 locus instead of the chromosome 3 locus, while also taking chromosome 8q into account.