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.

COMPARING THE OUTCOME OF SINGLE VERSUS MULTIPLE SESSION LASER PHOTOABLATION OF FLAT NEOVASCULARIZATION IN ZONE 1 AGGRESSIVE POSTERIOR RETINOPATHY OF PREMATURITY: A Prospective Randomized Study.

PURPOSE: To compare single versus 2-session laser photoablation for flat neovascularization in cases with Zone 1 aggressive posterior retinopathy of prematurity. METHODS: Twenty-nine Asian Indian infants with aggressive posterior retinopathy of prematurity were randomized; each eye received 1 of 2 methods (29 each in Group A or B) proposed by the PHOTO-ROP group. Group A underwent single session laser to the avascular retina underlying the flat neovascularization by direct laser over the fronds. Group B underwent laser in 2 sessions; first, laser was delivered to the avascular periphery up to the flat neovascularization and 7 days later to the avascular bed exposed by the retraction of the fronds. Outcome and complications between the two groups were compared. RESULTS: Mean birthweight and gestational ages were 1,276 g and 30.1 weeks, respectively. All eyes showed favorable outcome at a minimum 12-month follow-up. Hemorrhages after laser (41.4% vs. 17.2%, P < 0.001) were more common in the single laser group. Large hemorrhages (>1 disk diameter) seen in Group A took longer than 8 weeks to resolve and developed focal fibrosis. CONCLUSION: This study demonstrates that the two-staged laser procedure produces fewer and smaller hemorrhages and no fibrosis compared with a single session. Both methods have comparable favorable outcomes in Asian Indian infants.

Web-based telemonitoring of visual function and self-reported postoperative outcomes in cataract care: international multicenter randomized controlled trial.

PURPOSE: To compare 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 patients with cataract were randomized into 2 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- to 6-week postoperative 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 with conventional Early Treatment Diabetic Retinopathy Study 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 in spherical equivalent 0.15 ± 0.67 diopters), resulting in a poorer corrected distance VA compared with subjective refraction (mean 0.1 vs -0.1 logMAR). Rates of adverse events and unscheduled consultations were minimal across both groups. Preoperative and postoperative PROM questionnaires had a 100% response rate. Visual functioning (Catquest-9SF and National Eye Institute Visual Function Questionnaire-25) improved postoperatively (mean improvement -0.80 and 16.70, respectively) and did not significantly differ between the 2 groups. CONCLUSIONS: The patients with cataract in this study effectively provided postoperative outcome data using 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.

The Accuracy of a Web-Based Visual Acuity Self-assessment Tool Performed Independently by Eye Care Patients at Home: Method Comparison Study.

BACKGROUND:  Telehealth solutions can play an important role in increasing access to eye care. Web-based eye tests can enable individuals to self-assess their visual function remotely without the assistance of an eye care professional. A web-based tool for self-assessing visual acuity (VA) has previously been studied in controlled, supervised conditions. The accuracy of this tool when performed independently by patients in their home environment, using their own devices, has not yet been examined. OBJECTIVE:  The objective of this paper was to examine the accuracy of a web-based tool with respect to measuring VA in ophthalmic patients in their home environment, compared with a conventional in-hospital assessment using a Snellen chart (the gold standard). METHODS:  From April through September 2020, consecutive adult patients with uveitis at the University Medical Center Utrecht, the Netherlands, performed the web-based VA test at home (the index test) before their upcoming conventional VA assessment at the hospital (the reference test). The agreement between the 2 tests was assessed by the Bland-Altman analysis. Additional analyses were performed to investigate associations between clinical characteristics and the accuracy of the web-based test. RESULTS:  A total of 98 eyes in 59 patients were included in the study. The difference in VA between the index and reference tests was not significant, with a mean difference of 0.02 (SD 0.12) logMAR (P=.09) and 95% limits of agreement of -0.21 to 0.26 logMAR. The majority of the differences (77%) fell within the predetermined acceptable deviation limit of 0.15 logMAR. In addition, no patient characteristics or clinical parameters were found to significantly affect the accuracy of the web-based test. CONCLUSIONS:  This web-based test for measuring VA is a valid tool for remotely assessing VA, also when performed independently by patients at home. Implementation of validated web-based tools like this in the health care system may represent a valuable step forward in revolutionizing teleconsultations and can provide individual patients with the opportunity to self-monitor changes in VA. This is particularly relevant when the patient's access to ophthalmic care is limited. Future developments should focus on optimizing the testing conditions at home to reduce outliers.

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.

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.

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.

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.

Impact of Bevacizumab on Visual Function, Tumor Size, and Toxicity in Pediatric Progressive Optic Pathway Glioma: A Retrospective Nationwide Multicentre Study.

BACKGROUNDS: Bevacizumab (BVZ) is used as a subsequent line of treatment for pediatric optic pathway glioma (OPG) in the case of progression. Data on the treatment effect concerning tumor progression and visual function are scarce and nationwide studies are lacking. METHODS: We performed a retrospective, nationwide, multicentre cohort study including all pediatric patients with OPG treated with BVZ in the Netherlands (2009-2021). Progression-free survival, change in visual acuity and visual field, MRI-based radiologic response, and toxicity were evaluated. RESULTS: In total, 33 pediatric patients with OPG were treated with BVZ (median 12 months). Visual acuity improved in 20.5%, remained stable in 74.4%, and decreased in 5.1% of 39 of all analysed eyes. The monocular visual field improved in 73.1%, remained stable in 15.4%, and decreased in 7.7% of 25 analysed eyes. Radiologic response at the end of therapy showed a partial response in 7 patients (21.9%), minor response in 7 (21.9%), stable disease in 15 (46.9%), and progressive disease in 3 (9.3%). Progression-free survival at 18 and 36 months after the start of BVZ reduced from 70.9% to 38.0%. Toxicity (≥grade 3 CTCAE) during treatment was observed in five patients (15.2%). CONCLUSION: Treatment of BVZ in pediatric patients with OPG revealed stabilisation in the majority of patients, but was followed by progression at a later time point in more than 60% of patients. This profile seems relatively acceptable given the benefits of visual field improvement in more than 70% of analysed eyes and visual acuity improvement in more than 20% of eyes at the cessation of BVZ.

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.

Comparison of the intermediate distance of a trifocal IOL with an extended depth-of-focus IOL: results of a prospective randomized trial.

PURPOSE: To compare visual outcomes, reading ability, and visual quality between the Symfony extended depth-of-focus intraocular lens (IOL) and the trifocal AT LISA tri 839MP IOL. SETTING: University Eye Clinic Maastricht, The Netherlands. DESIGN: Prospective randomized controlled trial. METHODS: Patients were randomly assigned to bilateral Symfony IOL or AT LISA tri 839MP IOL implantation. The primary outcome measure was uncorrected intermediate visual acuity (UIVA measured at 66 cm). Secondary outcomes included uncorrected distance visual acuity (UDVA), uncorrected near visual acuity (UNVA), reading ability, and comparison of defocus curves, contrast sensitivity, optical adverse effects, and quality of vision. RESULTS: The study enrolled 60 eyes of 30 patients. The mean UIVA was -0.02 ± 0.03 (SD) vs 0.01 ± 0.03 logarithm of the minimal angle of resolution (logMAR) in the Symfony and AT LISA tri 839MP groups, respectively (P = .047). The UDVA was 0.01 ± 0.12 and -0.05 ± 0.07 logMAR (P = .11) and the UNVA was 0.09 ± 0.05 and 0.04 ± 0.07 logMAR (P = .052) in the Symfony and AT LISA tri 839MP groups, respectively. Reading ability was similar in both groups at 40 cm and 66 cm (P = .87 and P = .14, respectively). Less than 10% of patients in both groups experienced disabling glare. Patients experienced disabling halos in the AT LISA tri 839 MP group compared to the Symfony group in 39% and 21% of cases, respectively (P = .12). The mean score for visual functioning was 88.0 ± 14.1 n the trifocal group and 88.2 ± 10.9 for the EDOF group (P = .96). CONCLUSIONS: The UIVA was better in the Symfony group than in the AT LISA tri 839MP group. No significant differences were seen in the binocular UNVA and UDVA, contrast sensitivity, reading ability, incidence of photopic phenomena, and patient satisfaction.

Phakic intraocular lenses: An overview.

Phakic intraocular lenses (pIOLs) are a common solution for the surgical correction of high myopia and myopia in thin corneas. Global trends result in increasing rates of patients with high myopia which will result in increased rates of pIOL implantation. Three types of lenses can be distinguished: anterior chamber angle-supported, anterior chamber iris-fixated, and posterior chamber phakic IOLs. The efficacy of phakic intraocular lenses is generally very good, but pIOLs have undergone many changes over the years to improve the safety profile and decrease pIOL-related complications such as endothelial cell loss, corneal decompensation and cataract formation. This article describes the efficacy and safety profiles of the most recent pIOLs, as well as suggests gaps of knowledge that are deserve additional research to optimize the results of pIOLs.

Spectral Domain Optical Coherence Tomography in Detecting Sub-Clinical Retinal Findings in Asian Indian Children with Down Syndrome.

Purpose: Trisomy 21, also known as Down syndrome (DS), is the most common trisomy worldwide. Although ocular associations have been reported, retinal anatomy and pathology remain uninvestigated. We evaluate the role of spectral domain optical coherence tomography (SD-OCT) in analyzing foveal morphology of children with DS. Methods: Nineteen consecutive DS children and eight controls were enrolled under a cross-sectional study in an institutional practice. All subjects underwent SD-OCT imaging on a hand-held device. The morphology and thickness of central fovea, inner retinal layers, outer retina, and photoreceptor layers were measured and compared with age-group sub-analysis. Results: Mean age of the cases was 24 months (3-78 months). All cases and controls had a normal fundus on ophthalmoscopy and foveal thickness was comparable (p = 0.718). Inner retinal fusion was complete in the foveal center in only three eyes (15.8%) of cases compared to all eyes (100%) of controls (p < 0.001). The outer plexiform layer was normal in 10 eyes of cases (52.6%) compared to all eyes (100%) of the controls. Only 10 eyes of DS (52.6%) had a normal external limiting membrane, compared to all eyes of controls (100%, p = 0.01). The interdigitation zone (outer segment) was normal in one (5.3%) case compared to eight (67%) controls (p = 0.001). On subgroup analysis, in older cohorts, cases had a greater proportion of abnormal layers compared to controls. Visual acuity was found to be lower in cases when compared to controls, although not significant (p = 0.19). Conclusion: DS babies have abnormal foveal morphology and persistence of inner retinal layers. This may assist our understanding of their visual development.

Retinal immaturity at first screening and retinopathy of prematurity: Image-based validation of 1202 eyes of premature infants to predict disease progression.

Purpose: To use the extent of retinal immaturity at the first visit to predict progression to any stage and treatment-requiring retinopathy of prematurity (ROP). Methods: Retrospective, multicenter, nonrandomized, observational, clinical, validation study. In all, 601 Asian Indian preterm infants born < 2000 g and/or < 34 weeks of gestation completing ROP screening with RetCam images taken during each visit were included. A total of 1202 eyes of these infants were classified into three groups based on the retinal immaturity at the first screening visit into "mild" (Group 1), vessels reaching the posterior boundary of zone 3; "moderate" (Group 2), vessels entering zone 2 anterior; and "severe" (Group 3), vessels in zone 1 or zone 2 posterior. RetCam images at each subsequent visit were evaluated and the proportion of eyes that progressed to Type 1 or Type 2 ROP was correlated with the degree of retinal immaturity. Results: Of the 958 eyes in Group 1, 200 eyes in Group 2, and 44 eyes in Group 3, any stage ROP developed in 15% of eyes in Group 1, 46.5% of eyes in Group 2, and 100% of eyes in Group 3 (P < 0.001). Sixteen of 128 eyes (12.5%), 12 of 72 (16.6%), and 28 of 44 of eyes (63.6%) in Groups 1, 2, and 3, respectively, required treatment (P < 0.001). Conclusion: Retinal immaturity at first screening visit predicts Type 1 and Type 2 ROP. "Severe" immaturity is more likely to progress to "treatment-requiring" disease. This could be a useful tool for prognostication, counseling, and scheduling follow-up.