Five-year follow-up of a posterior chamber phakic intraocular lens with a central hole for correction of myopia.

PURPOSE: To evaluate intermediate and long-term visual outcomes and safety of a phakic intraocular posterior chamber lens with a central hole (ICL V4c) for myopic eyes. METHODS: Retrospective, consecutive case study of patients that uneventfully received a ICL V4c for myopia correction, with a 5-year postoperative follow-up. Department of Ophthalmology, Goethe University Frankfurt, Germany. RESULTS: From 241 eyes that underwent ICL implantation, we included 45 eyes with a mean age at surgery of 33 years ± 6 (18-48 years), with a 5 years follow-up. CDVA improved from 0.05logMAR ± 0.15 CDVA preoperatively to - 0.00 ± 0,07 at 5 years and did not change significantly from 3 to 5 years' time (p = 0.266). The mean spherical equivalent (SE) improved from -10.13D ± 3.39 to - 0.45D ± 0.69. The change in endothelial cell count showed a mean decrease of 1.9% per year throughout the follow-up. Safety and efficacy index were 1.16 and 0.78, respectively. Cataract formation was seen in 2 of 241 eyes (0.8%), but in none of the 45 eyes that finished the 5-year follow-up. CONCLUSIONS: Our data show a good intermediate and long-term stability, efficiency, and safety of ICL V4c phakic lenses in myopic eyes comparable to other known literature.

Retinal Toxicity of Medical Devices Used during Vitreoretinal Surgery: A Critical Overview.

Retinal toxicity/biocompatibility of medical devices in direct contact with the retina is an important subject for clinicians and scientists. As these effects are not very frequent, there is also a relative lack of information for many clinicians. The past has taught us multiple times that there is a significant safety problem associated with severe loss of vision in affected patients. In this review, we want to classify medical products that are used in the back of the eye, describe recent examples of toxicity, critically reflect on the regulations that exist and suggest improvements that can be done to ensure patient safety without hindering innovation. METHODS: Critical review of the recent papers and personal experience of the authors in this issue. Medical devices used in the back of the eye and recent examples of toxicity are described, regulations that exist are critically reflected and improvements suggested that can ensure patient safety without hindering innovation. RESULTS: There is clear evidence of toxicity after intraocular surgery in any category. Some cytotoxic indirect methods have failed in detecting this toxicity. Some ISO rules do not seem appropriate. Postmarketing safety is missing. There is little data on this issue. CONCLUSIONS: The absence of a clear regulation of the production, purification and evaluation of the toxic effects of the medical devices supposes the possibility that products are not sufficiently safe to obtain the CE mark.

Funduscopic versus HRT III Confocal Scanner Vertical Cup-Disc Ratio Assessment in Normal Tension and Primary Open Angle Glaucoma (The Leuven Eye Study).

PURPOSE: To compare funduscopic and confocal scanning vertical cup-disc ratio (VCDR) assessments and their respective predictive value for estimating functional glaucomatous damage. METHODS: Data from a single eye of open angle glaucoma patients from the Leuven Eye Study were included: age, gender, intra-ocular pressure, visual acuity, refractive error, visual field mean deviation and pattern standard deviation, funduscopic and HRT III VCDRs as well as mean retinal nerve fibre layer thickness. Non-parametric tests to compare differences within and between diagnostic groups were used, and receiver-operating characteristic curves as well as Bland-Altman plots constructed. RESULTS: Three hundred and one eyes of 301 subjects with primary open angle glaucoma (POAG) and normal tension glaucoma (NTG) were included. The average VCDR assessed with HRT III was significantly smaller than the funduscopic measurement (0.69 ± 0.16 vs. 0.81 ± 0.14, respectively; p < 0.001). The predictive value of both measurement techniques did not differ in NTG patients, but the funduscopic estimate yielded a significantly larger predictive power in patients with severe POAG. CONCLUSION: Funduscopic and confocal scanner estimates of VCDR differ significantly and should not be used interchangeably. In POAG patients with severe glaucoma, a subjective VCDR predicts functional glaucomatous damage significantly better.

More Than Meets the Eye: Klebsiella pneumoniae Invasive Liver Abscess Syndrome Presenting with Endophthalmitis.

BACKGROUND: Endophthalmitis is a feared complication of pyogenic liver abscesses caused by hypervirulent Klebsiella pneumoniae strains. First described in East Asia in the 1980s, this invasive syndrome is only recently emerging in Europe and America. CASE REPORT: We describe an 84-year-old man who presented to the emergency department with fever, orbital cellulitis, and bilateral visual loss. Although the patient had no overt abdominal symptoms, computed tomography scan revealed a pyogenic liver abscess. Blood cultures were positive for K. pneumoniae. Initial treatment consisted of intravenous ceftriaxone and intravitreal ceftazidime. A unilateral vitrectomy was performed. The patient survived with severe visual sequelae. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: K. pneumoniae pyogenic liver abscess with metastatic endophthalmitis is a relatively new syndrome that should be considered in patients presenting with acute vision loss who appear septic, with or without abdominal complaints. Early recognition prohibits delays in lifesaving treatment.

Eye lens dosimetry in anesthesiology: a prospective study.

The eye lens is one of the most sensitive organs for radiation injury and exposure might lead to radiation induced cataract. Eye lens dosimetry in anesthesiology has been published in few clinical trials and an active debate about the causality of radiation induced cataract is still ongoing. Recently, the International Commission on Radiological Protection (ICRP) recommended a reduction in the annual dose limit for occupational exposure for the lens of the eye from 150 to 20 mSv, averaged over a period of 5 years, with the dose in a single year not exceeding 50 mSv. This prospective study investigated eye lens dosimetry in anesthesiology practice during a routine year of professional activity. The radiation exposure measured represented the exposure in a normal working schedule of a random anesthesiologist during 1 month and this cumulative eye lens dose was extrapolated to 1 year. Next, eye lens doses were measured in anesthesiology during neuro-embolisation procedures, radiofrequency ablations or vertebroplasty/kyphoplasty procedures. The eye lens doses are measured in terms of the dose equivalent H p(3) with the Eye-D dosimeter (Radcard, Poland) close to the right eye (on the temple). In 16 anesthesiologists, the estimated annual eye lens doses range from a minimum of 0.4 mSv to a maximum of 3.5 mSv with an average dose of 1.33 mSv. Next, eye lens doses were measured for nine neuro-embolisation procedures, ten radiofrequency ablations and six vertebroplasty/kyphoplasty procedures. Average eye lens doses of 77 ± 76 µSv for neuro-embolisations, 38 ± 34 µSv for cardiac ablations and 40 ± 44 µSv for vertebro-/kyphoplasty procedures were recorded. The maximum doses were respectively 264, 97 and 122 µSv. This study demonstrated that the estimated annual eye lens dose is well below the revised ICRP's limit of 20 mSv/year. However, we demonstrated high maximum and average doses during neuro-embolisation, cardiac ablation and vertebro-/kyphoplasty procedures. With radiation induced cataract being explained as a possible stochastic effect, without a threshold dose, anesthesiologists who regularly work in a radiological environment should remain vigilant and maintain radiation safety standards at all times. This includes adequately protective equipment (protection shields, apron, thyroid shield and leaded eye wear), keeping distance, routine monitoring and appropriate education.

Review on Dynamic Contour Tonometry and Ocular Pulse Amplitude.

Intraocular pressure (IOP) measurement is the cornerstone of the management of glaucoma patients. The gold standard for assessing IOP is Goldmann applanation tonometry (GAT). Recently, the dynamic contour tonometer (DCT) has become available. While both devices provide reliable IOP measurements, the results are not interchangeable. DCT has the advantage of measuring an additional parameter: ocular pulse amplitude (OPA). OPA is defined as the difference between systolic and diastolic IOP and represents the pulsatile wave front produced by the varying amount of blood in the eye during the cardiac cycle. It has been shown to vary with ocular structural parameters, such as axial length, corneal thickness, and ocular rigidity, as well as with systemic variables like heart rate, blood pressure, and left ventricular ejection fraction. Although the existence of some of these associations is still controversial, the clinical relevance of OPA has been consistently suggested, especially in glaucoma. Further research on this intriguing parameter could not only provide insight into glaucoma pathophysiology but also help integrate this variable into clinical practice.

The Relevance of Arterial Blood Pressure in the Management of Glaucoma Progression: A Systematic Review.

BACKGROUND: Glaucoma is one of the leading causes of global blindness and is expected to co-occur more frequently with vascular morbidities in the upcoming years, as both are aging-related diseases. Yet, the pathogenesis of glaucoma is not entirely elucidated and the interplay between intraocular pressure, arterial blood pressure (BP) and ocular perfusion pressure is poorly understood. OBJECTIVES: This systematic review aims to provide clinicians with the latest literature regarding the management of arterial BP in glaucoma patients. METHODS: A systematic search was performed in Medline, Embase, Web of Science and Cochrane Library. Articles written in English assessing the influence of arterial BP and systemic antihypertensive treatment of glaucoma and its management were eligible for inclusion. Additional studies were identified by revising references included in selected articles. RESULTS: 80 Articles were included in this systemic review. A bimodal relation between BP and glaucoma progression was found. Both high and low BP increase the risk of glaucoma. Glaucoma progression was, possibly via ocular perfusion pressure variation, strongly associated with nocturnal dipping and high variability in the BP over 24 h. CONCLUSIONS: We concluded that systemic BP level associates with glaucomatous damage and provided recommendations for the management and study of arterial BP in glaucoma. Prospective clinical trials are needed to further support these recommendations.

Corrigendum: Progression of functional and structural glaucomatous damage in relation to diurnal and nocturnal dips in mean arterial pressure.

[This corrects the article DOI: 10.3389/fcvm.2022.1024044.].

Postoperative vault prediction for phakic implantable collamer lens surgery: LASSO formulas.

PURPOSE: To develop and evaluate reliable formulas for predicting postoperative vault more accurately after implantable collamer lens (ICL) surgery in a White patient population with varying degrees of ametropia. SETTING: Private clinical practice. DESIGN: Retrospective analysis on dataset split into a separate training and test set. METHODS: 115 eyes of 59 patients were used to train regression models predicting postoperative vault based on anterior segment optical coherence tomography (OCT) parameters (Least Absolute Shrinkage and Selection Operator [LASSO]-OCT formula), ocular biometry data (LASSO-Biometry formula), or data from both devices (LASSO-Full formula). The performance of these models was evaluated against the manufacturer's nomogram (Online Calculation and Ordering System [OCOS]) and Nakamura 1 (NK1) and 2 (NK2) formulas on a matched separate test set of 37 eyes of 19 patients. RESULTS: The mean preoperative spherical equivalent was -5.32 ± 3.37 (range: +3.75 to -17.375 diopters). The mean absolute errors of the estimated vs achieved postoperative vault for the LASSO-Biometry, LASSO-OCT, and LASSO-Full formulas were 144.1 ± 107.9 µm, 145.6 ± 100.6 µm, and 132.0 ± 86.6 µm, respectively. These results were significantly lower compared with the OCOS, NK1, and NK2 formulas ( P < .006). Postoperative vault could be estimated within 500 µm in 97.3% (LASSO-Biometry) to 100% of cases (LASSO-OCT and LASSO-Full). CONCLUSIONS: The LASSO suite provided a set of powerful, reproducible yet convenient ICL sizing formulas with state-of-the-art performance in White patients, including those with low to moderate degrees of myopia. The calculator can be accessed at http://icl.emmetropia.be .

Corneal Lenticule Creation Using a New Solid-State Femtosecond Laser Measured by Spectral Domain OCT in a Porcine Eye Model.

Purpose: To determine the accuracy and precision of corneal lenticule creation with a new solid-state femtosecond laser in a porcine eye model. Methods: Corneal lenticule creation was performed using a new solid-state femtosecond laser on 60 porcine eyes with 10 subgroups. Optical coherence tomography images were acquired immediately after laser treatment. Cap thickness (CT), cap diameter (CD), and lenticule thickness (LT) were measured manually by three independent readers. Additionally, CT and LT were measured by an automated algorithm (aLT, aCT). Results: Measured LT was significantly greater than the intended LT (average difference 14.3 ± 5.6 µm, P < 0.001). aLT was closer but still significantly different from the intended LT (-2.9 ± 5.8 µm, P < 0.001). Measured CT showed no significant difference from the intended CT (2.6 ± 13.3, P = 0.145). aCT was significantly smaller compared to the intended CT (-9.6 ± 13.6, P < 0.001). Measured CD was significantly smaller compared to the intended CD (-0.21 ± 0.20 mm, P < 0.001). All lenticules were cut as planned with no laser-related complications. Conclusions: This new solid-state femtosecond laser used in our trial provides corneal lenticule creation in a porcine eye model comparable to other established systems. However, measuring those lenticules in the provided setting seems too challenging even when using semiautomated algorithms, which seems to be due to the experimental setting of the trial. Translational Relevance: This trial shows the precision and repeatability of corneal cuts performed by a new femtosecond laser that could translate to refractive corneal lenticule surgery.

Age-related changes in the fractal dimension of the retinal microvasculature, effects of cardiovascular risk factors and smoking behaviour.

PURPOSE: This cross-sectional study investigates the association between retinal vessel complexity and age and studies the effects of cardiovascular health determinants. METHODS: Retinal vessel complexity was assessed by calculating the box-counting fractal dimension (Df ) from digital fundus photographs of 850 subjects (3-97 years). All photographs were labelled as 'non-pathological' by the treating ophthalmologist. RESULTS: Statistical models showed a significantly decreasing relationship between age and Df (linear: R-squared = 0.1897, p < 0.0001; quadratic: R-squared = 0.2343, p < 0.0001; cubic: R-squared = 0.2721, p < 0.0001), with the cubic regression model offering the best compromise between accuracy and model simplicity. Multivariate cubic regression showed that age, spherical equivalent and smoking behaviour have an effect (p < 0.0001) on Df . A significantly increasing effect of the number of pack-years on Df was observed (effect: 0.0004, p = 0.0017), as well as a significantly decreasing effect of years since tobacco abstinence (effect: -0.0149, p < 0.0001). CONCLUSION: We propose using a cubic trend with age, refractive error and smoking behaviour when interpreting retinal vessel complexity.

Ray-tracing Calculation Using Scheimpflug Tomography of Diffractive Extended Depth of Focus IOLs Following Myopic LASIK.

PURPOSE: To evaluate a ray-tracing formula for intraocular lens (IOL) calculation of diffractive extended depth of focus IOLs after myopic laser in situ keratomileusis (LASIK) compared to formulas from an established online calculator. METHODS: This retrospective, consecutive case series included patients after cataract surgery with implantation of an extended depth of focus (EDOF) IOL (AT LARA, Carl Zeiss Meditec; Symfony, Johnson & Johnson) and a history of myopic LASIK. Preoperative assessments included biometry (IOLMaster; Carl Zeiss Meditec) and corneal tomography, including true net power (TNP) (Pentacam; Oculus Optikgeräte GmbH). To evaluate the measurements, the simulated keratometry values (SimK) were compared to the TNP. Regarding IOL calculation, the mean prediction error, mean and median absolute prediction error (MAE and MedAE), and number of eyes within ±0.50, ±1.00, and ±2.00 diopters (D) from the Haigis-L, Shammas, and Barrett True K No History formulas to the Potvin-Hill and Haigis with TNP (Pentacam) formulas were compared. RESULTS: Thirty-six eyes matched the inclusion criteria with a mean spherical equivalent of -6.26 ± 3.25 diopters (D) preoperatively and -0.79 ± 0.75 D postoperatively. The mean difference from SimK and TNP was significantly different from zero (P < .001; -1.24 ± 0.81 D). The best performing formulas by MedAE were the Potvin-Hill and Barrett True K No History (0.39 ± 0.78 and 0.64 ± 1.00 D). The formula with the most eyes within ±0.50 D was the Potvin-Hill (64%), followed by the Barrett True K No History (44%). For MAE and percentage of eyes within ±0.50 D, the Potvin-Hill formula was significantly better than the Haigis-L, Shammas, and Haigis-TNP formulas (P < .05). CONCLUSIONS: Calculation of IOLs in patients who had LASIK remains less predicable than calculations for virgin eyes. Using ray-tracing to calculate diffractive EDOF IOLs after myopic LASIK, the Potvin-Hill formula outperformed established formulas in terms of the percentage within target refraction and the MAE. [J Refract Surg. 2021;37(4):231-239.].

Systematic Review on Fractal Dimension of the Retinal Vasculature in Neurodegeneration and Stroke: Assessment of a Potential Biomarker.

Introduction: Ocular manifestations in several neurological pathologies accentuate the strong relationship between the eye and the brain. Retinal alterations in particular can serve as surrogates for cerebral changes. Offering a "window to the brain," the transparent eye enables non-invasive imaging of these changes in retinal structure and vasculature. Fractal dimension (FD) reflects the overall complexity of the retinal vasculature. Changes in FD could reflect subtle changes in the cerebral vasculature that correspond to preclinical stages of neurodegenerative diseases. In this review, the potential of this retinal vessel metric to serve as a biomarker in neurodegeneration and stroke will be explored. Methods: A literature search was conducted, following the PRISMA Statement 2009 criteria, in four large bibliographic databases (Pubmed, Embase, Web Of Science and Cochrane Library) up to 12 October 2019. Articles have been included based upon their relevance. Wherever possible, level of evidence (LOE) has been assessed by means of the Oxford Centre for Evidence-based Medicine Level of Evidence classification. Results: Twenty-one studies were included for qualitative synthesis. We performed a narrative synthesis and produced summary tables of findings of included papers because methodological heterogeneity precluded a meta-analysis. A significant association was found between decreased FD and neurodegenerative disease, mainly addressing cognitive impairment (CI) and dementia. In acute, subacute as well as chronic settings, decreased FD seems to be associated with stroke. Differences in FD between subtypes of ischemic stroke remain unclear. Conclusions: This review provides a summary of the scientific literature regarding the association between retinal FD and neurodegenerative disease and stroke. Central pathology is associated with a decreased FD, as a measure of microvascular network complexity. As retinal FD reflects the global integrity of the cerebral microvasculature, it is an attractive parameter to explore. Despite obvious concerns, mainly due to a lack of methodological standardization, retinal FD remains a promising non-invasive and low-cost diagnostic biomarker for neurodegenerative and cerebrovascular disease. Before FD can be implemented in clinic as a diagnostic biomarker, the research community should strive for uniformization and standardization.

The Prevalence of Undiagnosed Age-Related Sight-Threatening Diseases in Self-Proclaimed Healthy Individuals.

BACKGROUND: Age-related conditions such as glaucoma, age-related macular degeneration, diabetic retinopathy, and cataract have become the major cause of visual impairment and blindness in high-income countries. The aim of the current study is to investigate the prevalence of these eye diseases in a cohort of self-proclaimed healthy elderly and thus get a rough estimation of the prevalence of undiagnosed age-related eye conditions in the Belgian population. METHODS: Individuals aged 55 and older without ophthalmological complaints were asked to fill in a general medical questionnaire and underwent an ophthalmological examination, which included a biomicroscopic examination, intraocular pressure measurement, axial length measurement, and acquisition of fundus pictures and optical coherence tomography scans. Information regarding follow-up was collected in those who received the advice of referral to an ophthalmologist or the advice to have more frequent follow-up visits, based on their study evaluation. RESULTS: The cohort included 102 people and comprised 46% men (median age 70 years, range 57-85 years). Referral for additional examinations was made in 26 participants (25%). The advice to have more regular follow-up ophthalmologist visits was given to nine additional participants (9%). No significant correlations between baseline characteristics and the need for referral could be identified. Follow-up information was available for 25 out of 26 referred volunteers. Out of these, four underwent a therapeutic intervention based on study referral, up until 18 months after study participation. All four interventions took place in the age group 65-74 years. CONCLUSIONS: This study shows that, even in an elderly population with self-proclaimed healthy eyes and good general health, a significant proportion of subjects showed ocular findings that need regular follow-up and/or intervention. The frequency of prior ophthalmological examinations does not seem to be relevant to this proportion, meaning that everyone above 55 years old needs a routine ophthalmological evaluation.

Structural analysis of retinal blood vessels in patients with COPD during a pulmonary rehabilitation program.

Cardiovascular diseases are frequently present in chronic obstructive pulmonary disease (COPD). Population-based studies found associations between retinal vessel diameters and cardiovascular health, but it is unknown whether this also applies to COPD patients. Therefore, we measured retinal vessel diameters in COPD patients and aimed to determine the association with cardiovascular risk factors, lung function, and functional outcomes. In addition, we investigated whether an exercise-based pulmonary rehabilitation (PR) program would change retinal vessel diameters, as a proxy for improved microvascular health. Demographics and clinical characteristics, including pulmonary function, exercise capacity, blood pressure, blood measurements and level of systemic inflammation were obtained from 246 patients during routine assessment before and after PR. Retinal vessel diameters were measured from digital retinal images. Older age and higher systolic blood pressure were associated with narrower retinal arterioles (ß: -0.224; p = 0.042 and ß: -0.136; p < 0.001, respectively). Older age, higher systolic blood pressure and lower level of systemic inflammation were associated with narrower retinal venules (ß: -0.654; -0.229; and -13.767, respectively; p < 0.05). No associations were found between retinal vessel diameters and lung function parameters or functional outcomes. After PR, no significant changes in retinal venular or arteriolar diameter were found. To conclude, retinal vessel diameters of COPD patients were significantly associated with systolic blood pressure and systemic inflammation, whilst there was no evidence for an association with lung function parameters, functional outcomes or other cardiovascular risk factors. Furthermore, an exercise-based PR program did not affect retinal vessel diameter.

Hyperspectral Imaging and the Retina: Worth the Wave?

Purpose: Hyperspectral imaging is gaining attention in the biomedical field because it generates additional spectral information to study physiological and clinical processes. Several technologies have been described; however an independent, systematic literature overview is lacking, especially in the field of ophthalmology. This investigation is the first to systematically overview scientific literature specifically regarding retinal hyperspectral imaging. Methods: A systematic literature review was conducted, in accordance with PRISMA Statement 2009 criteria, in four bibliographic databases: Medline, Embase, Cochrane Database of Systematic Reviews, and Web of Science. Results: Fifty-six articles were found that meet the review criteria. A range of techniques was reported: Fourier analysis, liquid crystal tunable filters, tunable laser sources, dual-slit monochromators, dispersive prisms and gratings, computed tomography, fiber optics, and Fabry-Perrot cavity filter covered complementary metal oxide semiconductor. We present a narrative synthesis and summary tables of findings of the included articles, because methodologic heterogeneity and diverse research topics prevented a meta-analysis being conducted. Conclusions: Application in ophthalmology is still in its infancy. Most previous experiments have been performed in the field of retinal oximetry, providing valuable information in the diagnosis and monitoring of various ocular diseases. To date, none of these applications have graduated to clinical practice owing to the lack of sufficiently large validation studies. Translational Relevance: Given the promising results that smaller studies show for hyperspectral imaging (e.g., in Alzheimer's disease), advanced research in larger validation studies is warranted to determine its true clinical potential.

Combination of snapshot hyperspectral retinal imaging and optical coherence tomography to identify Alzheimer's disease patients.

INTRODUCTION: The eye offers potential for the diagnosis of Alzheimer's disease (AD) with retinal imaging techniques being explored to quantify amyloid accumulation and aspects of neurodegeneration. To assess these changes, this proof-of-concept study combined hyperspectral imaging and optical coherence tomography to build a classification model to differentiate between AD patients and controls. METHODS: In a memory clinic setting, patients with a diagnosis of clinically probable AD (n = 10) or biomarker-proven AD (n = 7) and controls (n = 22) underwent non-invasive retinal imaging with an easy-to-use hyperspectral snapshot camera that collects information from 16 spectral bands (460-620 nm, 10-nm bandwidth) in one capture. The individuals were also imaged using optical coherence tomography for assessing retinal nerve fiber layer thickness (RNFL). Dedicated image preprocessing analysis was followed by machine learning to discriminate between both groups. RESULTS: Hyperspectral data and retinal nerve fiber layer thickness data were used in a linear discriminant classification model to discriminate between AD patients and controls. Nested leave-one-out cross-validation resulted in a fair accuracy, providing an area under the receiver operating characteristic curve of 0.74 (95% confidence interval [0.60-0.89]). Inner loop results showed that the inclusion of the RNFL features resulted in an improvement of the area under the receiver operating characteristic curve: for the most informative region assessed, the average area under the receiver operating characteristic curve was 0.70 (95% confidence interval [0.55, 0.86]) and 0.79 (95% confidence interval [0.65, 0.93]), respectively. The robust statistics used in this study reduces the risk of overfitting and partly compensates for the limited sample size. CONCLUSIONS: This study in a memory-clinic-based cohort supports the potential of hyperspectral imaging and suggests an added value of combining retinal imaging modalities. Standardization and longitudinal data on fully amyloid-phenotyped cohorts are required to elucidate the relationship between retinal structure and cognitive function and to evaluate the robustness of the classification model.

REFUGE Challenge: A unified framework for evaluating automated methods for glaucoma assessment from fundus photographs.

Glaucoma is one of the leading causes of irreversible but preventable blindness in working age populations. Color fundus photography (CFP) is the most cost-effective imaging modality to screen for retinal disorders. However, its application to glaucoma has been limited to the computation of a few related biomarkers such as the vertical cup-to-disc ratio. Deep learning approaches, although widely applied for medical image analysis, have not been extensively used for glaucoma assessment due to the limited size of the available data sets. Furthermore, the lack of a standardize benchmark strategy makes difficult to compare existing methods in a uniform way. In order to overcome these issues we set up the Retinal Fundus Glaucoma Challenge, REFUGE (https://refuge.grand-challenge.org), held in conjunction with MICCAI 2018. The challenge consisted of two primary tasks, namely optic disc/cup segmentation and glaucoma classification. As part of REFUGE, we have publicly released a data set of 1200 fundus images with ground truth segmentations and clinical glaucoma labels, currently the largest existing one. We have also built an evaluation framework to ease and ensure fairness in the comparison of different models, encouraging the development of novel techniques in the field. 12 teams qualified and participated in the online challenge. This paper summarizes their methods and analyzes their corresponding results. In particular, we observed that two of the top-ranked teams outperformed two human experts in the glaucoma classification task. Furthermore, the segmentation results were in general consistent with the ground truth annotations, with complementary outcomes that can be further exploited by ensembling the results.

Ophthalmic Outcome in a Belgian Cohort of Cystinosis Patients Treated with a Compounded Preparation of Cysteamine Eye Drops: Retrospective Analysis.

INTRODUCTION: Treatment of the anterior segment problems in cystinosis is challenging as oral cysteamine is ineffective in the treatment of corneal problems because of its avascular structure. Although cysteamine eye drops have been formulated to counter this issue, the stability of cysteamine in these off-licensed formulations and treatment compliance are major problems. The aim of this retrospective study was to determine the efficacy of a compounded preparation of aqueous 0.5% cysteamine eye drops in the management of corneal complications of cystinosis. METHODS: Data of patients attending the multidisciplinary cystinosis clinic at the University Hospitals Leuven, Belgium between January 2015 and December 2018 were analyzed. All cystinosis patients were treated with the compounded preparation of aqueous 0.5% cysteamine eye drops and oral cysteamine. RESULTS: A total of 12 patients were treated with the compounded preparation of aqueous 0.5% cysteamine eye drops, of whom 75% were aged > 18 years (n = 9). The mean instillation frequency of the cysteamine eye drops was 3.3 drops/eye per day, and the mean number of hospital visits was two per year. All patients showed photophobia, > 30% corneal infiltration, blepharospasm, eye pain and conjunctival hyperemia during the study period. None of these symptoms improved with treatment with aqueous compounded 0.5% cysteamine eye drops. The corneal cystine crystal score was ≥ 2 in all patients at the last  visit. CONCLUSION: Treatment with the compounded preparation of aqueous 0.5% cysteamine eye drops, combined with oral cysteamine, was not effective in reducing corneal cystine crystal deposition and other ocular symptoms in these patients with cystinosis. FUNDING: Recordati Rare Diseases.