Deep Learning Application to Detect Glaucoma with a Mixed Training Approach: Public Database and Expert-Labeled Glaucoma Population.

INTRODUCTION: Artificial intelligence has real potential for early identification of ocular diseases such as glaucoma. An important challenge is the requirement for large databases properly selected, which are not easily obtained. We used a relatively original strategy: a glaucoma recognition algorithm trained with fundus images from public databases and then tested and retrained with a carefully selected patient database. METHODS: The study's supervised deep learning method was an adapted version of the ResNet-50 architecture previously trained from 10,658 optic head images (glaucomatous or non-glaucomatous) from seven public databases. A total of 1,158 new images labeled by experts from 616 patients were added. The images were categorized after clinical examination including visual fields in 304 (26%) control images or those with ocular hypertension and 347 (30%) images with early, 290 (25%) with moderate, and 217 (19%) with advanced glaucoma. The initial algorithm was tested using 30% of the selected glaucoma database and then re-trained with 70% of this database and tested again. RESULTS: The results in the initial sample showed an area under the curve (AUC) of 76% for all images, and 66% for early, 82% for moderate, and 84% for advanced glaucoma. After retraining the algorithm, the respective AUC results were 82%, 72%, 89%, and 91%. CONCLUSION: Using combined data from public databases and data selected and labeled by experts facilitated improvement of the system's precision and identified interesting possibilities for obtaining tools for automatic screening of glaucomatous eyes more affordably.

Polymorphisms in CYP1B1 gene and the risk of suffering Primary Open-Angle Glaucoma: Systematic review and meta-analysis.

PURPOSE: It had been reported that mutations in CYP1B1 gene probably play an important role in the pathogenesis of primary open angle glaucoma (POAG) but the existing genetic association studies show contradictory results. Thus, the objective of our study was to perform a systematic review and meta-analysis to characterize more precisely the potential association between given polymorphisms in CYP1B1 gene and the risk of suffering POAG. METHODS: A systematic review of studies that related the risk of carrying CYP1B1 gene polymorphisms with POAG development was conducted. We selected 19 case-control studies including 3855 POAG patients and 4125 control subjects in our meta-analyses. A random effects model was used. Sensitivity analysis and assessment of bias were also included. RESULTS: The prevalence of CYP1B1 gene polymorphisms were significantly more frequent among POAG patients compared to all controls (OR = 2.91, 95% CI = 1.37 - 6.21; P = 0.006). Moreover, their prevalence was significantly higher in juvenile-onset patients than in adult-onset ones (OR = 2.27, 95% CI = 1.20-4.28; P = 0.001). CONCLUSION: The results of this meta-analysis uphold that being a carrier of polymorphic genetic variants in CYP1B1 gene would increase the risk of POAG, especially the juvenile onset.

Management and Systemic Implications of Diabetic Neovascular Glaucoma.

OBJECTIVES: To study the efficacy and safety of different treatments for diabetic neovascular glaucoma (NVG). We additionally attempt to determine if the presence of NVG could be a predictor of cardiovascular disease or death. METHOD: This is a retrospective, observational cohort study including patients diagnosed with diabetic NVG from 2006 to 2016 at the Hospital Clínico Universitario de Valladolid (Spain). Extracted data included clinical characteristics of the patients, glycated haemoglobin levels, and ocular treatment. Visual acuity (VA), intraocular pressure (IOP), cardiovascular events, and deaths were registered. RESULTS: 30 eyes from 23 patients were followed for a mean of 4.48 years (SD = 2.82 years). The IOP-lowering intervention groups were: Ahmed implant (11 eyes), laser cyclo-photocoagulation (CPC; 6 eyes), both (4 eyes), or none (9 eyes). IOP success was achieved in 100% of the eyes with Ahmed and/or laser CPC and in 44.4% of the eyes with no IOP-lowering procedure (p= 0.002). Most eyes with Ahmed implant (with or without CPC) maintained or improved their VA (100 and 63.6%, respectively). 33.3% of the eyes with laser CPC and 25% of those with no IOP-lowering intervention maintained or improved their VA (p = 0.028). Hypotony was the only adverse effect (after laser CPC). No statistically significant difference could be established between low VA (finger count or worse), poor IOP control, or bad metabolic control and mortality or cardiovascular event (p > 0.05), however, the four patients who died had poor VA at the time of NVG diagnosis. CONCLUSIONS: Ahmed implant surgery is a safe and effective treatment option for diabetic NVG. Medical treatment alone is not the best option for most cases. Advanced NVG could be an indicator of higher mortality risk in diabetic patients.

Association between SNPs of Metalloproteinases and Prostaglandin F2α Receptor Genes and Latanoprost Response in Open-Angle Glaucoma.

PURPOSE: To determine whether single nucleotide polymorphisms (SNPs) of genes coding for matrix metalloproteinases (MMPs) and the prostaglandin F2α receptor gene (PTGFR) are related to a response to latanoprost in a white Spanish population of glaucomatous patients. DESIGN: Case-control study. PARTICIPANTS: One hundred twenty-four patients with open-angle glaucoma. METHODS: Genotyping was performed in 117 patients with primary open-angle glaucoma with a minimum treatment duration of 4 weeks. Candidate genes and individual polymorphisms were selected according to the effect on the mechanism of action of latanoprost. Multi-SNP haplotype analyses for associations also were tested. MAIN OUTCOME MEASURES: Diurnal intraocular pressure reduction and genotyping of the SNPs in the MMPs and PTGFR. RESULTS: The PTGFR SNPs were associated with positive (rs6686438, rs10786455) and negative (rs3753380, rs6672484, rs11578155) responses to latanoprost. Multiple testing found 2 genes, PTGFR and MMP-1, were related to refractoriness to latanoprost. CONCLUSIONS: The SNPs of the PTGFR and MMP-1 genes may determine the latanoprost response in a white European Spanish population. This study identified 5 SNPs related to the latanoprost response; 1 SNP, rs3753380, already has been associated with a poor response to latanoprost in a healthy Japanese population. Latanoprost is a commonly used antiglaucomatous drug, and increased knowledge of its mechanism of action will lead to advances in pharmacogenetics.

Can we measure mesopic pupil size with the cobalt blue light slit-lamp biomicroscopy method?

BACKGROUND: The aim of this work is to assess a previously described slit-lamp biomicroscopy-based method (SLBM) for measuring pupil diameter and compare it to Colvard infrared pupillometry (CIP). METHODS: Two examiners performed three repeated measurements with each instrument in 40 healthy eyes. We determined the agreement of SLBM and CIP, intraobserver and interobserver repeatabilities, and interobserver concordance (kappa) and SLBM ability for detecting pupil sizes over 6.0 mm. RESULTS: The mean (±standard deviation [SD]) pupil diameter was 5.81 ± 0.70 mm with SLBM and 6.26 ± 0.68 mm with CIP (p = 0.01) averaging both examiner's results. Mean differences between the SLBM and CIP were -0.60 mm and -0.30 mm for each examiner using the average of the three readings (p = 0.02), and they were very similar using the first reading. Intraobserver reproducibility: the width of the 95% LoA ranged from 1.79 to 2.30 mm. The ICCs were 0.97 and 0.92 for SLBM, and 0.96 and 0.90 for CIP. Interobserver reproducibility: the width of the LoA ranged from 1.82 to 2.09 mm. Kappa statistics were 0.39 and 0.49 for the first and mean SLBM readings, respectively, and 0.45 for both the first and mean CIP readings. Sensitivity and specificity of SLBM for detection of pupils larger than 6 mm ranged from 55.56% to 73.68% and from 76.19% to 95.45%, respectively. The best trade-off between sensitivity and specificity ranged from 5.4 mm to 6.2 mm. CONCLUSIONS: Although the SLBM is quite repeatable, it underestimates mesopic pupil size and shows a too wide range of agreement with CIP. SLBM shows low sensitivity in detecting pupils larger than 6 mm, which may be misleading when planning anterior segment surgery. Previous grading-consensus training strategies may increase interrater reproducibility, and compensation for the systematic underestimation could improve accuracy of the SLBM.

Flap tearing during lift-flap laser in situ keratomileusis retreatment.

A flap tear occurred during laser in situ keratomileusis (LASIK) retreatment using a flap-lifting technique in 1 eye of 2 patients 4 to 5 months after the primary procedure. In the first case, the tear occurred in a decentered, standard thickness flap (168 mum) in a location close to the corneal limbus and limbal vessels. In the second case, the tear occurred in a well-centered thin flap (116 mum) that involved a peripheral corneal pannus. The false track was identified early, and central extension of the tear was averted. After the flap was successfully dissected, retreatment was performed without further complications. This report suggests that flaps with margins near the limbus or a corneal pannus may be prone to an earlier and stronger healing process at the edge that may lead to a flap tear during LASIK retreatment. This may be of increasing importance because of the trend toward larger flap diameters.

Subtarsal flap dislocation after superior hinge laser in situ keratomileusis in a patient with borderline mental illness.

PURPOSE: To report a case of complete subtarsal flap dislocation after uncomplicated superior hinge laser in situ keratomileusis (LASIK). METHODS: Flap dislodgement resulted from eye rubbing in a patient with a past medical history of mental illness and epilepsy. The dislocated cap, which was also folded in half, was refloated, profusely irrigated, and ironed to eliminate flap wrinkles. Particular care was taken to avoid flap misalignment. RESULTS: Despite the above mentioned intervention, a prominent epithelial mark corresponding to the line of previous folding persisted for 3 additional days. Eventually, a perfectly aligned lenticule without wrinkles and an otherwise normal postoperative course occurred. CONCLUSIONS: Although superior hinge LASIK may reduce the likelihood of flap displacement, mechanical forces can generate complete flap dislocation. When a flap has been folded in half, an epithelial mark corresponding to the line of folding may persist. Patients with psychiatric disorders may be at higher risk of postoperative flap-related complications.

Extensive corneal epithelial defect associated with internal hordeolum after uneventful laser in situ keratomileusis.

This report illustrates a retrospective case review in which extensive corneal epithelial ulceration occurred concomitantly with an internal hordeolum in the inferior forniceal conjunctiva 24 hours after an uneventful laser in situ keratomileusis. The internal hordeolum and epithelial defect were successfully managed using a bandage soft contact lens, a course of topical dexamethasone and tobramycin, and generous lubrication.