Remote follow-up after cataract surgery (CORE-RCT): study protocol of a randomized controlled trial.

BACKGROUND: Cataract surgery has become one of the most performed surgical procedures worldwide. Postoperative management consists of routine clinical examinations to assess post-operative visual function and detect possible adverse events. Due to the low incidence of complications, the majority of clinic visits after cataract surgery are uneventful. Nonetheless, valuable time and hospital resources are consumed. We hypothesize that remote post-operative follow-up involving teleconsultations and self-assessments of visual function and health status, could be a valid alternative to face-to-face clinical examinations in selected patient groups. The practice of remote follow-up after cataract surgery has not yet been evaluated. The aim of this study is to investigate the validity, safety and cost-effectiveness of remote cataract surgery follow-up, and to report on the patients' experiences with remotely self-assessing visual function. METHODS: This study is a multicenter, open-label, randomized controlled trial. Patients planned for cataract surgery on both eyes, without ocular comorbidities, are eligible for participation. Participants will be allocated (1:1) into one of the two study groups: 'telemonitoring' or 'usual care'. Participants in the 'telemonitoring' group will perform in-home assessments after cataract surgery (remote web-based eye exams and digital questionnaires on their own devices). Participants in the 'usual care' group will have regular post-operative consultations, according to the study site's regular practice. Outcome measures include accuracy of the web-based eye exam for assessing visual acuity and refraction, patient-reported outcome measures (visual function and quality of life), adverse events, and cost aspects. DISCUSSION: Investigating remote follow-up after cataract surgery fits the current trends of digitization of health care. We believe that remote self-care can be a promising avenue to comply with the increasing demands of cataract care. This randomized controlled trial provides scientific evidence on this unmet need and delivers the desired insights on (cost)effectiveness of remote follow-up after cataract surgery. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04809402. Date of registration: March 22, 2021.

Ocular findings in 22q11.2 deletion syndrome: A systematic literature review and results of a Dutch multicenter study.

The 22q11.2 deletion syndrome (22q11.2DS) is a multisystem disorder with an estimated prevalence of 1:3000 live births. Manifestations show a marked variability in expression and include speech- and language delay, intellectual disability, and neuropsychiatric disorders. We aim to provide an overview of ocular findings in 22q11.2DS in order to optimize recommendations for ophthalmic screening. We combined results from a systematic literature review with results from a multicenter cross-sectional study of patients with 22q11.2DS who were assessed by an ophthalmologist. Our systematic literature search yielded four articles, describing 270 patients. We included 132 patients in our cross-sectional study (median age 8.9 [range 0-56] years). Most reported ocular findings were retinal vascular tortuosity (32%-78%), posterior embryotoxon (22%-50%), eye lid hooding (20%-67%), strabismus (12%-36%), amblyopia (2%-11%), ptosis (4%-6%), and refractive errors, of which hyperopia (6%-48%) and astigmatism (3%-23%) were most common. Visual acuity was (near) normal in most patients (91%-94%). Refractive errors, strabismus, and amblyopia are treatable conditions that are frequently present in patients with 22q11.2DS and should be corrected at an early stage. Therefore, in 22q11.2DS, we recommend ophthalmic and orthoptic screening at the age of 3 years or at diagnosis, and a low-threshold referral in adults.

Long-Term Endothelial Cell Loss in Patients with Artisan Myopia and Artisan Toric Phakic Intraocular Lenses: 5- and 10-Year Results.

PURPOSE: To evaluate the long-term change in endothelial cell density (ECD) after the implantation of 2 types of rigid iris-fixated phakic intraocular lenses (pIOLs) for the treatment of myopia and astigmatism. DESIGN: Prospective, clinical cohort study. PARTICIPANTS: A total of 507 eyes of 289 patients receiving the Artisan Myopia or Artisan Toric (Ophtec B.V., Groningen, The Netherlands) iris-fixated pIOL for the treatment of myopia or astigmatism at the University Eye Clinic Maastricht as of January 1998. METHODS: A total of 381 myopic and 126 toric pIOLs were implanted. Five- and 10-year follow-ups were completed by 193 and 127 eyes implanted with the myopic pIOL and by 40 and 20 eyes implanted with the toric pIOL, respectively. MAIN OUTCOME MEASURES: Chronic endothelial cell (EC) loss, percentage of eyes with a decrease of ≥25% in ECD, and percentage of eyes with an ECD <1500 cells/mm2. RESULTS: Chronic EC loss was calculated from 6 months postoperatively to the end of follow-up and showed an annual ECD decline of 48 cells/mm2 (standard error, 3.14) and 61 cells/mm2 (standard error, 6.30) in the myopic (P < 0.001) and toric (P < 0.001) groups, respectively, resulting in a total EC loss of 16.6% and 21.5% from 6 months to 10 years postoperatively, respectively. Ten years after implantation, ECD had decreased by ≥25% in 7.9% and 6.3%, whereas ECD was <1500 cells/mm2 in 3.9% and 4.0% in the myopic and toric groups, respectively. Explantation of the pIOL occurred in 6.0% in the myopic group and 4.8% in the toric group. Risk factors for increased EC loss were a shallow anterior chamber depth (ACD) (P ≤ 0.005) and a smaller distance between the central and peripheral pIOL edge to the endothelium (P ≤ 0.005). CONCLUSIONS: A significant linear chronic EC loss was reported after implantation with myopic or toric iris-fixated pIOLs. A smaller ACD and smaller distance between pIOL edge and endothelium were risk factors for EC loss. Modification of preoperative age-related ECD thresholds is indicated to maintain an ECD that warrants safe future combined pIOL explantation and cataract surgery.

[Analysis of positive margins risk factors and long term recurrence in the conservative treatment of breast cancer]. / Analyse des facteurs de risque des marges positives et de la récidive à long terme dans le traitement conservateur du cancer du sein.

INTRODUCTION: breast conserving therapy remains the first choice in breast cancer care for the early stages. Adequate surgical margins are essential to reduce the risk of locoregional recurrence. This study aims to identify risk factors of positive margins and locoregional recurrence. MATERIALS AND METHODS: 437 patients who underwent a lumpectomy for invasive breast carcinoma or ductal carcinoma in situ have been included. Age, surgical margins, size, type, grade and number of tumor foci, the presence of ductal carcinoma in situ, lymph node status, expression of hormone receptors and HER-2 gene were assessed as risk factors for positive margins and locoregional recurrence. RESULTS: The disease-free survival is 94 % at 10 years. Patients with positive margins have lower survival (92 %) than those with negative margins (96 %) (p £ 0.05). Lobular and multifocal tumors are at risk of positive margins. Tumors with positive margins, T2, grade III, triple negative and HER-2 positive neoplasms are at risk of locoregional recurrence while the expression of hormone receptors is a protective factor for local recurrence. CONCLUSION: It appears in our study that invasive lobular and multifocal tumors may present positive surgical margins. Studies on pre- operative work-up are needed. Biological factors of the tumor seem to play a fundamental role in the locoregional recurrence or persistence of the tumor.

INTRODUCTION: Le traitement conservateur du sein reste le premier choix dans la prise en charge du cancer du sein pour les stades précoces. Des marges chirurgicales adéquates sont fondamen- tales pour diminuer le risque de récidive locorégionale. Cette étude vise à définir les facteurs de risque des marges positives et de récidive locorégionale. Matériel et méthode : 437 patientes ayant bénéficié d'une tumorectomie pour carcinome mammaire invasif ou carcinome canalaire in situ ont été incluses. L'âge, les marges chirurgicales, la taille, le type, le grade et le nombre de foyers tumoraux, la présence de carcinome canalaire in situ, l'état ganglionnaire, l'expression des récepteurs hormonaux et du gène HER-2 ont été évalués comme facteurs de risque de marges positives et de récidive locorégionale. Résultats : La survie sans récidive est de 94 % à 10 ans. Les patientes ayant des marges positives ont une survie moindre (92 %) que celles ayant des marges négatives (96 %) (p £ 0,05). Les tumeurs lobulaires et multifocales sont à risque de marges positives. Les tumeurs en marges positives, T2, de grade III, triples négatives et HER-2 positives sont à risque de récidive locorégionale tandis que l'expression des récepteurs hormonaux est un facteur protecteur de récidive locorégionale. CONCLUSION: Il apparaît dans notre étude que les tumeurs lobulaires invasives et multifocales risquent de présenter des marges chirurgicales positives. Des études sur la mise au point préopératoire sont nécessaires. Les facteurs biologiques de la tumeur semblent jouer un rôle fondamental dans la récidive locorégionale ou la persistance de la tumeur.

[Post operative complications after neoadjuvant systemic therapy in primary breast cancer treatment - Case-control study]. / Complications post-opératoires après chimiothérapie néo-adjuvante dans le traitement du cancer du sein - étude cas-contrôle.

The use of neoadjuvant systemic therapy (NST) for the primary breast cancer treatment has constantly increased. Initially used to improve breast-conserving surgery (BCS) rate as well as for patients with inflammatory or inoperable locally advanced breast cancer, today, NST is used as a test of chemosensitivity and predictive factor by assessing pathologic complete response. With the increasing use of NST, it is fundamental to establish if NST increases postoperative morbidity.. In our study, the postoperative complications associated with NST were examined. We analyzed the data obtained from patients undergoing treatment for breast cancer in a University Hospital between 2003-2014 in a case-control study. We selected 286 patients attributed to two groups according to the surgery type: Group A, 150 patients undergoing breast conserving surgery with axillary node dissection (75 cases after NST and 75 controls with surgery alone) and group B, 136 patients undergoing mastectomy with axillary node dissection (68 cases after NST and 68 controls). There was no statistically significant difference between both groups in post-operative recovery or the rates of complications: use of antibiotics, re-operation, hematoma, blood transfusion, healing problems, wound infection, lymphocele and lymphoedema. Our study supports the safety of NST and suggests that it is not associated with increased morbidity in the patients undergoing breast surgery as BSC or mastectomy with axillary node dissection.

L'utilisation de la chimiothérapie néo-adjuvante (ChTN) dans le traitement du cancer mammaire est en constante augmentation. Au début, utilisée pour améliorer le taux de chirurgie conservatrice ainsi que dans la prise en charge de la mastite inflammatoire ou d'un cancer localement trop avancé pour une chirurgie en première ligne, à l'heure actuelle la réponse à la ChTN est un facteur prédictif de la chimiosensibilité1. Vu son utilisation plus fréquente, il est fondamental de savoir si la ChTN n'augmente pas la morbidité post-opératoire. Nous avons étudié les complications postopératoires associées à la ChTN et analysé les patients traités pour cancer mammaire à l'Hôpital Erasme entre 2004 et 2013 dans une étude cascontrôle. Nous avons sélectionné 286 patients répartis en un groupe A de 150 patients opérés d'une tumorectomie avec curage axillaire (75 cas post ChTN et 75 contrôles) et un groupe B de 136 patients opérés d'une mastectomie avec curage axillaire (CA), (68 cas opérés post ChTN et 68 contrôles). Nous n'avons pas remarqué de différence significative entre les groupes ni dans l'évolution ni dans la survenue de complications post-opératoires : prise d'antibiotiques, reprise opératoire, présence d'hématome, infection, lymphocèle, nécessité de transfusion, troubles de cicatrisation, apparition de lymphœdème. Notre étude suggère que la ChTN n'est pas associée à un taux plus élevé de complications postopératoires.

[Belgian register and reference centers for gestational trophoblastic diseases]. / REGISTRE BELGE ET CENTRES DE RÉFÉRENCE POUR LES MALADIES TROPHOBLASTIQUES GESTATIONNELLES.

Gestational trophoblastic diseases include placental pathologies comprising fertilization abnormalities (hydatidiform moles) and malignant lesions (choriocarcinoma, placental site trophoblastic tumor and epithelioid trophoblastic tumor). Due to their low incidence and heterogeneity, their diagnosis, management and treatment are not always optimal. Following the example of other European countries, a national registration system with two reference centers has been set up to guide physicians and patients and to propose individualized management. The centers offer their expertise through a systematic centralised pathology review by a panel of experts. HCG values are plotted in regression curves. In case of gestational trophoblastic neoplasia, an imaging work-up is proposed, from which the FIGO score and stage are derived and will guide the choice of treatment. Belgian centers offer a multidisciplinary approach, in partnership with the referent physician. More information for practitioners and patients is available on a web site: www.mole-chorio-bgog.eu, which also harbours a forum of discussion.

[Preventing cervical cancer]. / La prévention du cancer du col utérin.

The incidence of cervical cancer has hopefully been dropping down in our industrialized countries since the introduction of both primary and secondary prevention. Nevertheless, it is still lethal in one out of two affected women though the introduction of cytological screening has dramatically reduced the mortality. Progressive diffusion of anti-HPV vaccination, the broadening of the viral types concerned, its association with existing screening measures and finally the introduction of viral detection as a screening tool must optimize the results already obtained.

Gastric endometriosis associated with transverse colon endometriosis: a case report of a very rare event.

Gastric endometriosis is a very rare event. It enters in the differential diagnosis of cyclical or chronic epigastric pain, especially in the context of endometriotic patients. The diagnosis of a gastric submucosal mass requires further investigations to rule out the presence of malignancy or associated adenocarcinoma. Because of it can be associated with transverse colon endometriosis and/or diaphragmatic endometriosis, careful examination of the upper abdomen at laparoscopy should be emphasized. We report here a very rare case of gastric endometriosis associated with transverse colon endometriosis.

Web-based Telemonitoring of Visual Function and Self-reported Postoperative Outcomes in Cataract Care: an International Multicenter RCT.

PURPOSE: Comparing web-based, self-administered follow-up after cataract surgery to conventional face-to-face follow-up. SETTING: Eye clinics in the Netherlands, Austria and Germany. DESIGN: Randomized controlled trial with an embedded method comparison study [ClinicalTrials.gov: NCT04809402]. METHODS: Routine cataract patients were randomized into two groups: the 'telemonitoring' group undertook web-based vision self-assessments and questionnaires from home, while the 'usual care' group received conventional care. All participants had a 4-6 week post-surgery clinic visit for safety and validation purposes. Outcomes included: the web-test's accuracy for assessing postoperative visual acuity (VA) and refractive error; adverse event rates; and patient reported outcome measurements (PROMs). RESULTS: 94 participants (188 eyes) were enrolled. Web-based uncorrected distance VA testing demonstrated a negligible mean difference (-0.03±0.14 logMAR) when compared to conventional ETDRS chart testing, with 95% limits-of-agreement ranging from -0.30 to 0.24 logMAR. The web-based refraction assessment overestimated the postoperative refractive error (mean difference 0.15±0.67 diopters), resulting in a poorer corrected distance VA compared to subjective refraction (mean 0.1 vs. -0.1 logMAR). Rates of adverse events and unscheduled consultations were minimal across both groups. Preoperative and postoperative PROMs questionnaires had a 100% response rate. Visual functioning (Catquest-9SF and NEI-VFQ-25) improved after surgery (mean improvement -0.80 and 16.70 respectively) and did not significantly differ between the two groups. CONCLUSION: The cataract patients in this study effectively provided postoperative outcome data via a web-interface. Both conventional and web-based follow-ups yielded similar PROMs and adverse event rates. Future developments should reduce the variability in the web-based VA test and yield representative refraction outcomes.

Evaluation of a visual acuity eHealth tool in patients with cataract.

PURPOSE: To validate the Easee web-based tool for the assessment of visual acuity in patients who underwent cataract surgery. SETTING: University Eye Clinic Maastricht, Maastricht, the Netherlands. DESIGN: Prospective method comparison study. METHODS: Subjects aged between 18 and 69 years who underwent cataract surgery on 1 or both eyes at the Maastricht University Medical Center+ were eligible to participate in this study. The uncorrected (UDVA) and corrected distance visual acuity (CDVA) assessments were performed using the web-based tool (index test) and conventional ETDRS and Snellen charts (reference tests). The outcomes of the different tests were expressed in logMAR, and a difference of <0.15 logMAR was considered clinically acceptable. RESULTS: 46 subjects with 75 operated eyes were included in this study. The difference of the UDVA between the web-based tool and ETDRS or Snellen was -0.05 ± 0.10 logMAR ( P < .001 [0.15; -0.26]) and -0.04 ± 0.15 logMAR ( P = .018 [0.24; -0.33]), respectively. For the CDVA, these differences were -0.04 ± 0.08 logMAR ( P < .001 [0.13; -0.21]) and -0.07 ± 0.10 logMAR ( P < .001 [0.13; -0.27]), respectively. The Pearson correlation coefficients between the web-based tool and ETDRS were maximally 0.94 and compared with Snellen 0.92. In total, 73% to 88% of the visual acuity measurement differences were within 0.15 logMAR. CONCLUSIONS: The web-based tool was validated for the assessment of visual acuity in patients who underwent cataract surgery and showed clinically acceptable outcomes in up to 88% of patients. Most of the participants had a positive attitude toward the web-based tool, which requires basic digital skills.

Residual astigmatism following toric intraocular lens implantation related to pupil size.

PURPOSE: To present two patients with residual astigmatism following toric intraocular lens (IOL) implantation. METHODS: Case reports. RESULTS: A 58-year-old woman underwent toric IOL implantation (spherical power 29.50 diopters [D], cylinder power 3.00 D; SN60T5, Alcon Laboratories Inc) to correct 2.33 D @ 80° of corneal astigmatism. Postoperatively, uncorrected distance visual acuity (UDVA) was 20/30 and corrected distance visual acuity (CDVA) was 20/22 (0 -1.75 × 95), indicating an overcorrection of astigmatism. Slit-lamp examination demonstrated no IOL misalignment. Wavefront aberrometry showed a large pupil diameter (>6 mm) and a lower corneal astigmatism in a 6-mm zone (-1.40 D @ 174°) compared to a 4-mm zone (-2.21 D @ 171°). The second patient, a 60-year-old man, underwent multifocal toric IOL implantation (spherical power 22.50 D, cylinder power 2.25 D; SND1T4, Alcon Laboratories Inc) to correct 1.51 D @ 173° of corneal astigmatism. Postoperatively, UDVA was 20/50 and CDVA was 20/20 (+0.25 -1.00 × 102), indicating an undercorrection of astigmatism. Slit-lamp examination showed no misalignment. CONCLUSIONS: Both cases indicate that unexplained residual astigmatism following toric IOL implantation may be the result of multiple factors: the effect of the spherical power and anterior chamber depth on toric IOL calculations, the effect of posterior corneal astigmatism, and the effect of a large pupil size. The first two issues may be compensated for by improving toric IOL calculations. The latter indicates that pupillometry is indicated in relatively young patients who undergo toric IOL implantation.

Clinical outcomes of treatment with idebenone in Leber's hereditary optic neuropathy in the Netherlands: A national cohort study.

PURPOSE: The purpose of the study was to present results from a national Dutch cohort of patients with Leber's Hereditary Optic Neuropathy (LHON) treated with idebenone. METHODS: The multicentre, open-label, retrospective evaluation of the long-term outcome of idebenone treatment of Dutch LHON patients on visual function and on thickness of the retinal ganglion cell layer. Patients included in the analysis had a confirmed mutation in their mitochondrial DNA encoding either of the seven subunits of complex I, had a reported loss of vision in at least one eye and had a follow-up of more than 6 months after their treatment was started. Control visits involved routine clinical examinations of visual function and retinal structure at (1) the start of treatment, (2) nadir (time of lowest visual acuity), (3) the time of recovery (if any), (4) the time of termination of treatment and (5) more than 6 months after termination of the treatment. RESULTS: Data from 72 patients were analysed. Treatment duration was 23.8 ± 14.4 (mean ± SD) months. A positive response, that is either a clinically relevant recovery (CRR) or a clinically relevant stabilization (CRS), occurred in 53% and 11% of the patients, respectively. The magnitude of CRR was 0.41 ± 1.54 logMAR. CRR of visual acuity is associated with recovery of colour discrimination. The thickness of both the ganglion cell complex (GCC) and the retinal nerve fibre layer (RNFL) is irreversibly reduced. CONCLUSION: Our results confirm that idebenone may help to restore or maintain visual function. Whether this effect will persist is still unknown. Thinning of retinal neural tissue appears to be permanent.

Changes in visual outcomes and ocular morphometrics after foldable myopic and toric intraocular lens implantation: 5-year results.

PURPOSE: To evaluate the refractive, visual, and morphometric changes after implantation with a foldable iris-fixated phakic intraocular lens (pIOL) to correct myopia or astigmatism. SETTING: University Eye Clinic Maastricht, the Netherlands. DESIGN: Prospective case series. METHODS: We evaluated patients implanted with the Artiflex Myopia Toric (Ophtec B.V.) iris-fixated pIOL as of January 2004. Measurements were performed annually and reported after 1 and 5 years. RESULTS: The study included 481 eyes (277 patients; age 39.8 ± 10.9 years [SD]). 5 years postoperatively, 91% of eyes were within ±1.0 diopter (D) of target, and the mean myopization over a 5-year period was 0.22 D (P < .001). The logMAR corrected distance visual acuity (CDVA) increased by a mean 0.015 (P = .015) over 5 years; 88% of eyes had a CDVA of 20/20 or better, and 5.5% lost 2 or more lines of CDVA. Mean uncorrected distance visual acuity (UDVA) increased by 0.045 logMAR over 5 years (P < .001); 96% reached an UDVA of 20/40 or more. Anterior chamber depth (ACD) decreased by 0.04 mm (P < .001), and axial length (AL) increased by 0.23 mm (P < .001) over 5 years. Chronic endothelial cell loss showed a 5-year decline of 320 cells/mm2 in the myopic and 310 cells/mm2 in the toric subgroups (P < .001). Cataract resulted in pIOL explantation in 4.0% of eyes (mean survival 59.0 ± 40.0 months); higher preoperative age (hazard ratio [HR], 1.13; P < .001) and smaller ACD (HR, 6.80; P = .035) were risk factors for shorter survival due to cataract formation. CONCLUSIONS: Over 5 years, logMAR CDVA and UDVA decreased significantly due to myopization caused by lenticular changes and AL elongation.

Visual outcomes of a new nondiffractive extended depth-of-focus intraocular lens targeted for minimonovision: 3-month results of a prospective cohort study.

PURPOSE: To evaluate visual outcomes, spectacle independence, and optical phenomena after bilateral implantation of a nondiffractive extended depth-of-focus (EDoF) intraocular lens (IOL) targeted for minimonovision. SETTING: University Eye Clinic Maastricht, the Netherlands. DESIGN: Prospective case series. METHODS: Patients with age-related cataract were bilaterally implanted with a nondiffractive EDoF IOL (Alcon AcrySof IQ Vivity), targeted for minimonovision. Outcome measures were the uncorrected distance visual acuity (UDVA), corrected distance visual acuity, uncorrected intermediate visual acuity (UIVA), uncorrected near visual acuity (UNVA), distance corrected intermediate visual acuity, distance corrected near visual acuity, refractive outcomes, defocus curves, spectacle independence, photic phenomena, and Catquest-9SF questionnaire. RESULTS: 44 eyes of 22 patients were included. The mean binocular UDVA, UIVA, and UNVA were -0.07 (±0.10), 0.04 (±0.09), and 0.23 (±0.12) logMAR, respectively. The percentage of eyes within ±1.0 diopters (D) and ±0.5 D of target was 100% and 95% for the dominant eye and 100% and 86% for the nondominant eye, respectively. The binocular defocus curve was better than 0.10 logMAR over a range from -2.0 D to +0.5 D. The percentage of patients who reported not or rarely using spectacles for distance, intermediate, and near viewing distance was 96%, 68%, and 38%, respectively. The percentage of patients who experienced no halos, glare, or starbursts were 91%, 91%, and 100%, respectively. The Catquest-9SF showed a high patient satisfaction for daily life activities. CONCLUSIONS: Bilateral AcrySof IQ Vivity IOL implantation targeted for minimonovision provided good visual acuity results for far and intermediate with functional near vision, high level of patient satisfaction and spectacle independence, and a monofocal disturbance profile.

Predictive accuracy of an intraoperative aberrometry device for a new monofocal intraocular lens.

PURPOSE: To evaluate refractive outcomes for the Clareon monofocal intraocular lens (IOL) in terms of achieved target refraction for the ORA (ALCON) intraoperative wavefront aberrometry device and preoperative noncontact biometry. SETTING: University Eye Clinic Maastricht, Maastricht University Medical Center+, the Netherlands. DESIGN: Prospective observational clinical trial. METHODS: Patients with bilateral age-related cataracts undergoing phacoemulsification, either by delayed sequential surgery or on the same day, were included in the study. Exclusion criteria were an increased risk for refractive surprise or complicated surgery. Implanted IOL power was based on noncontact optical biometry data using the Barrett Universal II (BU-II) formula, optimized for the Clareon IOL. Postoperative subjective refraction was measured 4 to 6 weeks after surgery. Catquest-9SF questionnaires were completed preoperatively and 3 months after surgery. RESULTS: 100 eyes (51 patients) were included. The percentages of eyes within 1.0 diopters (D), 0.75 D, 0.50 D, and 0.25 D of target for ORA vs BU-II were 84% (84 eyes), 72% (72 eyes), 57% (57 eyes), and 21% (21 eyes) vs 97% (97 eyes), 88% (88 eyes), 77% (77 eyes), and 53% (53 eyes), respectively. Mean absolute prediction error was significantly higher for ORA vs preoperative biometry (P < .001). After global optimization, the prediction accuracy of ORA improved significantly (P < .001). Catquest-9SF questionnaires showed improved levels of ability at 3 months after surgery (P < .001). CONCLUSIONS: This study showed lower percentages of eyes within target refraction for ORA (prior to lens constant optimization) compared with the BU-II formula when implanting the Clareon IOL. However, prediction accuracy of ORA improved significantly after global optimization. Therefore, further intraoperative measurements, postoperative measurements, and optimization are needed to improve the ORA prediction for this IOL.

Increased nerve density in deep infiltrating endometriotic nodules.

BACKGROUND/AIMS: Deep infiltrating endometriosis is a very painful condition and the mechanism of pain is still poorly understood. Pain and hyperalgesia can partly be explained by an increased number of nerve structures in the painful lesion. In order to clarify this issue, we assessed the nerve density in deep infiltrating endometriotic nodules of the posterior vagina and in the adjacent healthy vaginal tissue of the same patient. METHODS: A prospective clinical and pathological study of 31 cases of deep infiltrating vaginal endometriotic nodules was conducted. Fifteen patients were in the proliferative phase and 16 in the secretory phase. The nerve density was studied by immunohistochemistry with the monoclonal antibody NF against neurofilaments in deep infiltrating endometriosis and in the adjacent unaffected vaginal tissue in the proliferative and in the secretory phases. Neurofilaments constitute the main structural elements of neuronal axons and dendrites. RESULTS: The nerve density was significantly different in the endometriotic nodule than in the adjacent unaffected vaginal tissue (p = 0.0013). The same significant difference was found between endometriotic nodules and the unaffected vagina in the proliferative phase (p = 0.009) and in the secretory phase (p = 0.04). This difference was not significant between the proliferative and the secretory phases in the endometriotic lesions and in the controls. CONCLUSIONS: We hypothesize that the significantly increased number of nerve structures in the endometriotic nodules may contribute to the occurrence of severe and neuropathic pain that characterizes these lesions.

Biallelic Variants in the COLGALT1 Gene Causes Severe Congenital Porencephaly: A Case Report.

OBJECTIVE: We describe a third patient with brain small vessel disease 3 (BSVD3), being the first with a homozygous essential splice site variant in the COLGALT1 gene, with a more severe phenotype than the 2 children reported earlier. METHODS: Analysis of whole exome sequencing (WES) data of the child and parents was performed. We validated the missplicing of the homozygous variant using reverse transcription PCR and Sanger sequencing of the mRNA in a lymphocyte culture. RESULTS: The patient presented antenatally with porencephaly on ultrasound and MRI. Postnatally, he showed a severe developmental delay, refractory epilepsy, spastic quadriplegia, and a progressive hydrocephalus. WES revealed a homozygous canonical splice site variant NM_024656.3:c.625-2A>C. PCR and Sanger sequencing of the mRNA demonstrated that 2 cryptic splice sites are activated, causing a frameshift in the major transcript and in-frame deletion in a minor transcript. CONCLUSIONS: We report a third patient with biallelic pathogenic variants in COLGALT1, confirming the role of this gene in autosomal recessive BSVD3.

Chloroquine combined with concurrent radiotherapy and temozolomide for newly diagnosed glioblastoma: a phase IB trial.

Treatment of glioblastoma xenografts with chloroquine results in macroautophagy/autophagy inhibition, resulting in a reduction of tumor hypoxia and sensitization to radiation. Preclinical data show that EGFRvIII-expressing glioblastoma may benefit most from chloroquine because of autophagy dependency. This study is the first to explore the safety, pharmacokinetics and maximum tolerated dose of chloroquine in combination with radiotherapy and concurrent daily temozolomide in patients with a newly diagnosed glioblastoma. This study is a single-center, open-label, dose-finding phase I trial. Patients received oral chloroquine daily starting one week before the course of chemoradiation (temozolomide 75 mg/m2/d) until the end of radiotherapy (59.4 Gy/33 fractions). Thirteen patients were included in the study (n = 6: 200 mg, n = 3: 300 mg, n = 4: 400 mg chloroquine). A total of 44 adverse events, possibly related to chloroquine, were registered including electrocardiogram QTc prolongation, irreversible blurred vision and nausea/vomiting resulting in cessation of temozolomide or delay of adjuvant cycles. The maximum tolerated dose was 200 mg chloroquine. Median overall survival was 16 months (range 2-32). Median survival was 11.5 months for EGFRvIII- patients and 20 months for EGFRvIII+ patients. A daily dose of 200 mg chloroquine was determined to be the maximum tolerated dose when combined with radiotherapy and concurrent temozolomide for newly diagnosed glioblastoma. Favorable toxicity and promising overall survival support further clinical studies.Abbreviations: AE: adverse events; CQ: chloroquine; DLT: dose-limiting toxicities; EGFR: epidermal growth factor receptor; GBM: glioblastoma; HCQ: hydroxychloroquine; IDH1/2: isocitrate dehydrogenase (NADP(+)) 1/2; MTD: maximum tolerated dose; CTC: National Cancer Institute Common Toxicity Criteria; MGMT: O-6-methylguanine-DNA methyltransferase; OS: overall survival; po qd: per os quaque die; SAE: serious adverse events; TMZ: temozolomide; WHO: World Health Organization.

Increase in treatment of retinopathy of prematurity in the Netherlands from 2010 to 2017.

PURPOSE: Compare patients treated for Retinopathy of Prematurity (ROP) in two consecutive periods. METHODS: Retrospective inventory of anonymized neonatal and ophthalmological data of all patients treated for ROP from 2010 to 2017 in the Netherlands, subdivided in period (P)1: 1-1-2010 to 31-3-2013 and P2: 1-4-2013 to 31-12-2016. Treatment characteristics, adherence to early treatment for ROP (ETROP) criteria, outcome of treatment and changes in neonatal parameters and policy of care were compared. RESULTS: Overall 196 infants were included, 57 infants (113 eyes) in P1 and 139 (275 eyes) in P2, indicating a 2.1-fold increase in ROP treatment. No differences were found in mean gestational age (GA) (25.9 ± 1.7 versus 26.0 ± 1.7 weeks, p = 0.711), mean birth weight (791 ± 311 versus 764 ± 204 grams, p = 0.967) and other neonatal risk factors for ROP. In P2, the number of premature infants born <25 weeks increased by factor 1.23 and higher oxygen saturation levels were aimed at in most centres. At treatment decision, 59.6% (P1) versus 83.5% (P2) (p = 0.263) infants were classified as Type 1 ROP (ETROP classification). Infants were treated with laser photocoagulation (98 versus 96%) and intravitreal bevacizumab (2 versus 4%). Retreatment was necessary in 10 versus 21 (p = 0.160). Retinal detachment developed in 6 versus 13 infants (p = 0.791) of which 2 versus 6 bilateral (p = 0.599). CONCLUSION: In period 2, the number of infants treated according to the ETROP criteria (Type 1) increased, the number of ROP treatments, retinal detachments and retreatments doubled and the absolute number of retinal detachments increased. Neonatal data did not provide a decisive explanation, although changes in neonatal policy were reported.

Evaluation of accuracy of fine needle aspiration cytology in BI-RADS3 category breast lesions: cytohistological correlation in 337 cases.

OBJECTIVE: To evaluate the accuracy of fine needle aspiration cytology (FNAC) in BI-RADS3 breast lesions. METHODS: Between January 2004 and December 2007, 337 cases from BI-RADS3 lesions underwent FNAC. Three to six needle passes were made on each patient. In 67 cases (20%) a histological biopsy was performed. Cytological and histological interpretations were performed by the same pathologist. RESULTS: The histological diagnosis showed that 88% (59/67) of BI-RADS3 breast lesions were benign. Only 6% (4/67) were malignant, consisting of ductal carcinoma in situ and infiltrating ductal carcinoma. CONCLUSION: BI-RADS3 lesions remain disruptive in their management. However, the correlation between cytology and histology showed that most of these lesions were benign and that finally FNAC remains a useful and accurate test in the management of these lesions.