Retinal Nerve Fiber Layer Defects Research Articles

Optic nerve head factors associated with initial central visual field defect in primary open-angle glaucoma

We investigated optic nerve head factors associated with initial parafoveal scotoma (IPFS) in primary open-angle glaucoma. Eighty (80) patients with an IPFS and 84 patients with an initial nasal step (INS) were compared. Central retinal vascular trunk (CRVT) deviation from the Bruch’s membrane opening (BMO) center was measured as a surrogate of lamina cribrosa (LC)/BMO offset, and its obliqueness was defined as the absolute value of angular deviation from the fovea-BMO axis. Proximity of retinal nerve fiber layer defect (RNFLD) was defined as the angular deviation of the inner RNFLD margin from the fovea-BMO axis. Microvasculature dropout (MvD) was defined as a focal sectoral capillary dropout with no visible microvascular network identified in the choroidal layer. Factors associated with IPFS, as compared with INS, were assessed using logistic regression analyses and conditional inference tree analysis. The IPFS group had more oblique CRVT offset (P < 0.001), RNFLD closer to the fovea (P < 0.001), more MvD (P < 0.001), and more LC defects (P < 0.001) compared to the INS group. In logistic regression analyses, obliqueness of CRVT offset (P = 0.002), RNFLD proximity (P < 0.001), and MvD (P = 0.001) were significant factors influencing the presence of IPFS. Conditional inference tree analysis showed that RNFLD closer to the fovea (P < 0.001) in the upper level, more oblique CRVT offset (P = 0.013) and presence of MvD (P = 0.001) in the lower level were associated with the probability of having IPFS. IPFS was associated with closer RNFLD location to the fovea when assessed from the BMO. Oblique LC/BMO offset may not only mask RNFLD proximity to the fovea due to a deviated funduscopic disc appearance, but also potentiate IPFS via focal LC defect and MvD.

Vascular insufficiency leading to recurrent disc haemorrhage in normotensive glaucoma

Disc haemorrhage is a sign of progression in normotensive glaucoma. We report a case who was presented with right eye (RE) optic disc haemorrhage and retinal nerve fibre layer defect at first visit, he was diagnosed as normotensive glaucoma (NTG). On subsequent follow up visits he had recurrent disc haemorrage and progression in visual fields and optical coherence tomography (OCT). On further evaluation he had h/o of dehydration episodes as he lives in hotter climates and on systemic evaluation he had carotid stenosis and nocturnal dip in 24 hr blood pressure monitoring. This case tells about importance of systemic evaluation in normotensive glaucoma.

Long-term Follow-up of Myopic Glaucoma: Progression Rates and Associated Factors.

To investigate the progression rate of myopic glaucoma and associated factors by long-term analysis of its clinical course. Longitudinal observational study. Patients who had had at least 5 years of follow-up and a spherical equivalent of - 0.5 diopters or less were included in this study. They were divided into three myopia groups according to myopic grade, namely mild myopia (-0.5 to -3.0 diopters), moderate myopia (-3.0 to -6.0 diopters), and high myopia (-6.0 diopters or more), and the clinical course, progression rate, and associated factors were compared among the groups and analyzed. A total of 121 eyes of 121 glaucoma patients with myopia were included in the study. The average follow-up period was 10.4 ± 2.9 years. In the analysis of progression rate, the change rate of average retinal nerve fiber layer (RNFL) thickness [-0.75μm/yr in mild myopia, -0.82μm/yr in moderate myopia, -0.84μm/yr in high myopia] and the mean deviation change [-0.30dB/yr in mild myopia, -0.37dB/yr in moderate myopia, -0.39dB/yr in high myopia] both tended to be faster as the myopic grade increased. In a Kaplan-Meier survival analysis, the high myopia groups demonstrated a significantly faster visual acuity loss (of more than 3 lines) and a higher incidence of newly developed central visual field defect (CVFD) than did the mild and moderate myopia groups. Longer axial length (OR: 1.72, CI : 1.03 - 3.07, P = 0.047) and retinal nerve fiber layer defect (RNFLD) extending to the macula (OR: 4.14, CI : 1.54 - 12.30, P = 0.007) were significantly associated with newly developed CVFD. In myopic glaucoma patients, the higher the degree of myopia, the faster the rate of visual acuity loss and CVFD occurrence. Occurrence of CVFD was associated with longer axial length and widening of RNFLD to the macula.

Different glaucoma progression rates by age groups in young myopic glaucoma patients

We aimed to investigate the age-related glaucoma progression rates in myopic normal tension glaucoma (NTG). In this long-term retrospective cohort (7.2 ± 3.5 years), we grouped patients based on their age at initial presentation: group A (age < 30 years, 60 eyes), group B (30 ≤ age < 40, 66 eyes), and group C (40 ≤ age < 50 years, 63 eyes). We used a linear mixed-effects model to estimate retinal nerve fiber layer (RNFL) defect width enlargement rates. Group A showed a significantly faster rate of RNFL defect progression (3.01 ± 1.74°/year) than those of groups B and C (2.05 ± 1.55°/year and 2.06 ± 1.29°/year, P = 0.004 and 0.002). The difference was more marked when calculated for the first 10 years of follow-up in group A, B, and C (3.95 ± 2.70°/year, 2.39 ± 1.64°/year, and 1.98 ± 1.31°/year), and between the periods of age < 30 years, 30 ≤ age < 40 years, and 40 ≤ age < 50 years within group A. This is the first evidence of rapid glaucoma progression in the young adulthood and stabilization in older age in myopic NTG. Clinicians should consider the potentially aggressive course of glaucoma, especially in younger patients with myopic NTG, in contrast to the general slow progression in adulthood.

Clinical Characteristics and Associated Factors to the Development of Glaucoma in Eyes With Myopic Optic Neuropathy

PurposeTo observe the development of glaucoma in myopic eyes with and without myopic optic neuropathy (MON) and analyze associated factors to the development of typical glaucomatous damage. DesignA prospective, observational, cohort study MethodsA total of 233 myopic eyes with no definite evidence of glaucomatous damage were included in the study. Myopic patients without any retinal nerve fiber layer (RNFL) or visual field (VF) abnormalities were classified as myopic eyes without MON. Myopic patients with decreased RNFL at the superonasal (SN) or nasal area, and with corresponding VF defects either in the temporal or inferotemporal (IT) region, which is different from glaucomatous damage, were classified as myopic eyes with MON. Myopic eyes that developed glaucoma were defined by the presence of glaucomatous VF in the SN region including defects in Bjerrum area, or a new localized RNFL defect in the IT region on red-free photography or RNFL OCT. Disc morphological features and optic nerve head (ONH) parameters of two groups were compared. Hazard ratios for the association between baseline factors and conversion to glaucoma were obtained using Cox regression analysis. ResultsMean follow-up period was 11.66 ± 2.86 years. Myopic eyes with MON had a thinner average peripapillary RNFL thickness (P < 0.001), worse MD of the VF (P = 0.031), a higher percentage of IT VF defects (P < 0.001), smaller torsion degree (P = 0.047), and greater LCD (P = 0.022). Myopic eyes with MON who developed glaucoma had a thinner average peripapillary RNFL thickness (P = 0.009), greater PPA area (P = 0.049), greater LCD (P < 0.001), and thinner LCT (P < 0.001). Thinner baseline temporal RNFL thickness (HR, 0.956; 95% CI, 0.928–0.986; P = 0.004), greater baseline LCD (HR, 1.003; 95% CI, 1.000–1.005; P = 0.022), and greater PPA area (HR, 1.000; 95% CI, 1.000–1.003; P = 0.050) were significantly associated factors with glaucoma development in the Cox regression analysis. ConclusionMyopic eyes with MON have a greater risk to develop glaucoma compared to myopic eyes without MON. Myopic eyes with MON had larger PPA area, greater LCD, and thinner temporal peripapillary RNFL, indicating that accompanying structural weakness due to myopia, especially at the temporal side of the optic nerve head and the peripapillary sclera, increases the risk of glaucoma in myopic eyes with MON.

Clinical outcomes after implantation of a new monofocal intraocular lens with enhanced intermediate function in patients with preperimetric glaucoma.

We evaluated the clinical outcomes after implantation of a new monofocal intraocular lens (IOL) with enhanced intermediate function in patients with preperimetric glaucoma and compared those with patients without retinal nerve fiber layer (RNFL) defects. All patients were implanted bilaterally a new monofocal IOL with enhanced intermediate function. Patients with bilateral RNFL defects and no glaucomatous visual field defects were classified as the preperimetric glaucoma group. A total of 60 eyes of 30 patients with preperimetric glaucoma were compared with 60 eyes of 30 patients without RNFL defects. Uncorrected distance visual acuity (UDVA), uncorrected intermediate visual acuity (UIVA), uncorrected near visual acuity (UNVA), defocus curve, contrast sensitivity, and questionnaire were evaluated 1 month and 3 months after surgery. No difference in binocular UDVA, UIVA, and UNVA was evident between the two groups at 1 and 3 months postoperatively. Additionally, there were no significant differences between the two groups regarding the proportion of severe or very severe photic phenomena, such as glare and halos, or the overall satisfaction. Bilateral implantation of a new monofocal IOL with enhanced intermediate function in patients with preperimetric glaucoma demonstrated commensurate clinical outcomes and could be considered a feasible alternative.

Association between localized retinal nerve fibre layer defects and metabolic syndrome in nonglaucomatous eyes: A propensity score‐matched analysis

Aims/Purpose: To investigate the association between metabolic syndrome and localized retinal nerve fibre layer (RNFL) defects in nonglaucomatous subjects.Methods: We examined 20 385 adults at the Health Promotion Center in Seoul St. Mary's Hospital between May 2015 and April 2016. Subjects with and without localized RNFL defects were 1:5 propensity score matched. Metabolic syndrome components, central obesity, elevated triglyceride, reduced HDL cholesterol, elevated blood pressure and elevated fasting glucose, were compared between two groups. Logistic regression was performed to investigate the association between RNFL defects and each metabolic syndrome component as well as the number of metabolic syndrome components.Results: Subjects with RNFL defects showed higher waist to hip ratio, systolic and diastolic BP, fasting blood glucose and HbA1c compared to those without RNFL defects before and after propensity score matching. The number of metabolic syndrome components was significantly greater in those with RNFL defects (1.66 ± 1.35) compared to those without (1.27 ± 1.32, p &lt; 0.01). In multivariate logistic regression, the odds of RNFL defects were significantly increased in subjects with central obesity (OR = 1.53, 95% confidence interval [CI] = 1.11–2.13), elevated blood pressure (OR = 1.50, 95% CI = 1.09–2.05), and elevated fasting glucose (OR = 1.42, 95% CI = 1.03–1.97). Greater number of metabolic syndrome components was associated with higher odds of RNFL defects.Conclusions: The presence of localized RNFL defects in nonglaucomatous subjects is associated with metabolic syndrome components, including central obesity, elevated BP and elevated fasting glucose, suggesting that comorbid metabolic syndromes should be considered when evaluating subjects with RNFL defects.

External testing of an established glaucoma screening AI on a glaucoma clinic population from Finland

Purpose: To assess the external performance of an existing deep learning regression model for glaucoma detection (G‐RISK) in a glaucoma clinic population from Finland.Methods: Colour fundus images were retrospectively collected from the Tampere University Hospital (Tays), Finland. Eyes that had a visit in 2019 or 2020 were included based on the availability of ground truth labels. Ground truth labels for glaucoma were obtained through clinical evaluation of the optic nerve head (ONH) from colour fundus photos, clinical evaluation of retinal nerve fibre layer (RNFL) defects from fundus photos imaged with a cobalt filter, and clinical evaluation of the SITA Fast visual field (VF) test. Glaucoma diagnosis at Tays followed the ‘2 out of 3 rule’ recommended by the Finnish Evidence‐Based Guideline for Glaucoma, which requires at least 2 positive indications of glaucoma tests for referral [1]. Preprocessed colour fundus images were used as input to a previously trained deep learning model (G‐RISK) [2]. Performance was evaluated using the area under the receiver operating characteristic curve (AUC), accompanied by 95% confidence intervals. Patient aggregated results were obtained by comparing the maximum of both prediction and ground truth label.Results: Over 3000 patients had at least one ground truth available for a visit in 2019 or 2020. Clinical evaluation of structural features (ONH, RNFL) triggered more glaucomatous symptoms than the SITA Fast VF test. When thresholding the AI prediction against a single ground truth type, the best AUC was obtained on the ONH label (0.90 [0.89–0.91]), followed by RNFL (0.84 [0.83–0.86]) and VF (0.83 [0.81–0.84]). When implementing the 2 out of 3 rule, AUC reached 0.88 [0.82–0.90].Conclusion: The model performed best when using the ONH label and incorporating the ‘2 out of 3 rule’, reaching an AUC of 0.88. These findings suggest that the G‐RISK model could be a valuable tool for screening in clinical practice.

Radius-Maumenee Syndrome, A Rare Entity: A Case Report

Background: Radius–Maumenee syndrome (RMS) is a rare idiopathic condition characterized by the enlargement of episcleral vessels and an elevation in intraocular pressure (IOP) leading to secondary glaucoma. Case: In this report, we present a case of RMS in 23-year-old male who experienced redness in Right Eye (RE) and intermittent headaches for a duration of 10 years. The patient exhibited a best corrected visual acuity of 6/6 in both eyes. Observations: During slit lamp biomicroscopy, episcleral venous engorgement was observed in both eyes. Tonometry measured 28 mmHg in the RE and 14 mmHg in Left Eye (LE). In fundus photographs of RE and LE, there was evident cup asymmetry, along with retinal nerve fiber layer defects in superotemporal and inferotemporal regions of the right eye. Optical coherence tomography (OCT) Optic Nerve Head with hood report of RE showed loss of double hump pattern with asymmetric and severe retinal nerve fiber layer thinning in superior and inferior quadrant. Visual field testing of RE showed superior and inferior arcuate scotoma. Brain and orbit magnetic resonance angiography (MRI Angiogram) revealed no abnormal voids indicating cavernous fistula or other orbital lesions. The presence of secondary open angle glaucoma with episcleral venous engorgement and negative test results for other potential conditions led to the diagnosis of RMS in the patient. The patient is now under combination therapy with aqueous suppressants and uveoscleral outflow increasing drugs. Conclusion: This case serves as a reminder to ophthalmologists about potential association of glaucoma if there’s enlargement of episcleral vessels in eyes without inflammation.

Papillomacular bundle defect (PMBD) in glaucoma patients with high myopia: frequency and risk factors

Little is known about the papillomacular bundle defect (PMBD) in glaucoma. As such, we investigated the frequency of PMBD in glaucoma patients with high myopia, and its risk factors. In this retrospective, cross-sectional study, retinal nerve fiber layer (RNFL) defect was analyzed in 92 glaucomatous eyes with high myopia (axial length of 26.0 mm or more or an average spherical value of − 6.0 diopters or less). After dividing them into two groups with and without PMBD, the clinical characteristics of the groups were compared and analyzed. The mean age of the patients was 52.1 ± 10.5 years, and there were 53 males and 39 females. PMBD were observed in 55 eyes (59.8%). There was no significant intergroup difference in baseline or follow-up intraocular pressure (IOP). Parapapillary atrophy (PPA)-to-disc-area ratio (OR 3.83, CI: 1.58–10.27, p = 0.010), lamina cribrosa defect (LCD; OR 2.92, CI: 1.14–8.13, p = 0.031) and central visual field defect (CVFD; OR 3.56, CI: 1.38–9.58, p = 0.010) were significantly associated with the PMBD..

The Relationship between Transcranial Doppler Ultrasonography and Visual Field Test Results in Glaucoma and Glaucoma Suspect Patients.

To evaluate the relationships between parameters of transcranial ultrasonography and results of visual field tests in patients with open angle glaucoma or suspected of having glaucoma. This retrospective study was based on data from medical records of patients who visited the Department of Ophthalmology in __________ Hospital from January 1, 2016 to October 17, 2019 and underwent transcranial Doppler ultrasonography as part of a routine health examination. Ophthalmic data were visual acuity, intraocular pressure, optical coherence tomography (OCT), and Humphrey visual field test results. Retinal nerve fiber layer defect was confirmed by a glaucoma specialist. Patients' ophthalmic data, such as average ganglion cell layer thickness, visual field index (VFI), pattern standard deviation (PSD), and mean deviation (MD), were divided into quartiles. Each ophthalmic artery parameter from transcranial Doppler ultrasonography was compared between quartiles. A total of 162 patients were reviewed. There was no difference in Doppler ophthalmic artery (OA) parameters between patients with or without retinal nerve fiber layer defect. None of the quartile groups of average ganglion cell layer thickness showed significant difference in any OA parameters. Patients in the low-VFI quartile showed significant low peak systolic velocities of OAs when adjusted for age, gender, and presence of diabetes mellitus or hypertension (p = 0.016). A higher PSD showed lower peak systolic velocity (p = 0.046). There was no significant tendency between any other OA parameter and MD value. Our study suggests that hemodynamic parameters of ophthalmic arteries might be associated with visual field status of patients. Further large-population studies are needed in order to better understand the relationship between visual function and ocular blood flow.

Genetic risk of glaucoma is associated with vascular and retinal nerve fibre wedge defects.

To evaluate the association between localised vascular and retinal nerve fibre layer (RNFL) loss and genetic risk for glaucoma and cardiovascular disease using polygenic risk scores (PRS). 858 eyes were included from 455 individuals with suspect and early manifest primary open angle glaucoma. Eyes were characterised as having localised vascular and/or RNFL wedge-shaped defects by scrutiny of optical coherence tomography angiography (OCTA) and OCT images, respectively. Investigations included associations with pre-established scores for genetic risk of glaucoma and cardiovascular disease in the context of glaucoma risk factors and systemic vascular disease outcomes. Higher genetic risk for glaucoma was associated with both vascular wedge defects and RNFL defects (p < 0.001 and p = 0.020, respectively). A greater genetic risk of glaucoma was associated with the presence of multiple vascular wedges per eye (p = 0.005). Glaucoma progression based on global RNFL loss was associated with vascular and RNFL wedge defects (p ≤ 0.001 and p = 0.008, respectively). The glaucoma PRS was significantly associated with vascular, but not RNFL, wedge defects after controlling for disc haemorrhage (p = 0.007 and p = 0.070, respectively). Vascular wedge defects were not related to the cardiovascular PRS. Individuals with a higher genetic risk of glaucoma based on the PRS were more likely to have retinal vascular defects, as well as structural glaucomatous loss, but this did not relate to systemic cardiovascular risk. This possibly implies a local pathophysiology for the vascular defects in some cases, which may have clinical relevance in the early stages of glaucoma and in individuals at high genetic risk.

Deep Optic Nerve Head Morphology in Tilted Disc Syndrome and Its Clinical Implication on Visual Damage.

To study deep optic nerve head (ONH) morphology in tilted disc syndrome (TDS) and identify factors associated with retinal nerve fiber layer (RNFL) defect. In patients with TDS, we evaluated the optic disc shape using the Bruch's membrane opening (BMO)-anterior scleral canal opening (ASCO) offset and measured the border tissue (BT) length, depth, and angle in the direction of the tilt, using radial ONH optical coherence tomography (OCT). We compared the parameters between the TDS groups with and without RNFL defects. Twenty-one eyes had no glaucomatous RNFL defect, and 38 eyes had a glaucomatous RNFL defect. The group with RNFL defects had a higher baseline IOP, larger tilt axis of BMO-ASCO optic disc margin (76.4° ± 14.5° vs. 87.9° ± 15.4°, P = 0.012), larger BMO-lamina cribrosa insertion (LCI) angle (25.6° ± 9.3° vs. 43.6° ± 15.2°, P < 0.001), and more lamina cribrosa (LC) defects (4.3% vs. 30.6%, P = 0.028) than without RNFL defects. The tilt axis and BMO-LCI angle were significant factors after adjusting for baseline IOP and LC defect. The BMO-LCI angle had excellent diagnostic power for glaucomatous RNFL defect in TDS, similar to the visual field mean deviation. OCT-based large deep ONH BT angle and tilt axis were factors associated with the presence of RNFL defects in TDS. The results suggest a mechanism of RNFL defect associated with structural ONH deformation. Further investigations are warranted to understand the role of ONH structures in a general population with and without optic disc tilt.

Identification of Glaucoma in Diabetics Using the Laguna-ONhE Colourimetric Method and OCT Spectralis.

Previous retrospective results are evaluated prospectively and blinded. A total of 221 eyes previously classified as normal (G1), 279 as moderate risk of glaucoma (G2) and 217 as high risk (G3) according to the Globin Discriminant Function (GDF) Laguna-ONhE index were examined with OCT Spectralis- Results: In G1, the Bruch's Membrane Opening Minimum Rim Width (BMO-MRW) was 332 ± 55 microns; in G2, it was 252 ± 47 (p < 0.0001); and in G3, 231 ± 44 (p < 0.0001). In G1, the 1% and 5% percentiles were 233 and 248, respectively; in G2, they were lower in 28.80% and 42.29% of cases, respectively; and in G3, in 50.23% and 63.59% of cases, respectively. Most of the cases were normal-tension glaucomas. Laguna-ONhE indices showed a curvilinear correlation with BMO-MRW results. The Retinal Nerve Fibre Layer (RNFL) showed a poor relationship with BMO. Assuming G1 to be truly normal, BMO-MRW would have a Receiver operating characteristic (ROC) curve area of 0.901 for G2 and G3 and 0.651 for RNFL. A significant reduction in pixels corresponding to vessels was found in G2 and G3 vs. G1 (p < 0.0001). In some cases, these defects appear to be mainly glaucomatous, and in others, they are associated with diabetic microangiopathy. In normal tension glaucoma, RNFL defects may be less severe than those inside the nerve.

Synonymous Myocilin mutations break their silence in a Zambian population attending selected referral eye health facilities

Objective: Primary open-angle glaucoma in Zambia has an earlier age of onset and appears to be more clinically severe. Myocilin mutations are associated with primary open angle glaucoma in multiple populations. Therefore, we investigated the role of myocilin gene mutations in Primary Open Angle Glaucoma in a Zambian population. Methods: The unrelated primary open-angle glaucoma patients and unaffected controls recruited were from the University Teaching Hospitals Eye Hospital, Kitwe Teaching Eye Hospital and Lusaka Adventist Eye Hospital. A complete eye examination, including visual field assessment, was performed in all cases and controls.Genomic DNA was extracted from whole peripheral blood, then subjected to polymerase chain reaction to amplify exons, flanking introns and promoter regions of the myocilingene. The amplified products were screened for base mutations by auto sequence based on the Sanger method. The analyses of findings included odds ratios, chi-square, bivariate, multivariate and conditional logistic regression with 95% confidence interval and at a 5% level of significance.There was also a comparison between the identified mutations and the previously reported myocilinmutations. Results: Unrelated 165 Primary Open-Angle Glaucoma patients and unaffected 173 controls enrolled for the study. The analysis revealed 4 variants of MYOC mutations in 49 participants of the 338. The mutations included one synonymous (silent) mutation (Thr474Thr; 45/338) and three missense mutations (Ala446Thr; 16/338), (Leu158Arg; 4/338) and (Arg342Lys; 1/338). The study observed two previously reported mutations, Ala446Thr and Arg342Lys, as glaucoma causing mutations. The missense mutation, Ala446Thr, was found in 16 participants who also had silent mutations broken down as eight cases and eight controls. One control had two variants, Ala446Thr and Arg342Lys. Twenty (20) controls and 25 cases had the synonymous or silent (neutral) mutation, (Thr474Thr). The occurrence of Thr474Thr and Ala446Thr in the same cases and controls was compelling evidence to think that the synonymous mutations were not as silent as previously reported. The Thr474Thr and Ala446Thr mutations exhibited identical primary open-angle glaucomaphenotypic features in both cases and controls. In the remaining 17 cases and 12 controls the phenotype were still the same. The clinical profile in Thr474Thr mutation was statistically significant for female gender, younger age group (&lt;40 years), older age group (≥ 65 years), positive family history, poor visual acuity, severe visual field changes, diffuse retinal nerve fibre layer defects, peripapillary atrophy surrounding the optic nerve head and high cup disc ratio between 0.8 and 1.0 Conclusions: The silent myocilin mutations, Thr474Thr, break their silence in a Zambian population. The silent mutation Thr474Thr found was associated with primary open-angle glaucoma phenotype and appeared to be a glaucoma-causing.

Natural History of Optic Disc With Physiologic Large Cup: Incidence, Predictors of Glaucoma Conversion After Minimum 10-Year Follow-up

To investigate the natural history of optic disc with physiologic large cup (PLC) (ie, vertical cup/disc ratio [VCDR] ≥0.6 without retinal nerve fiber layer defect) and the risk factors for glaucoma conversion. Observational retrospective cohort study. Subjects who underwent a health screening examination at Seoul National University Hospital Healthcare System Gangnam Center from 2003 to 2010 (n=76,030) were involved. The prevalence of PLC in the cohort was analyzed. The incidence rate of glaucoma conversion was estimated per 100 person-years among cases with a follow-up period longer than 10 years. Multivariate Cox proportional hazards regression was used to identify ocular and systemic factors associated with glaucoma conversion. Among 74,617 eligible subjects, 3569 subjects (4.8%) had PLC. Of those with a follow-up period longer than 10 years (n=859), the incidence rate of glaucoma conversion was 0.95 per 100 person-years. A total of 12.1% of PLC eyes progressed to glaucoma after 8.7 ± 3.9 years (range, 2.0-16.5 years). Higher VCDR (adjusted hazard ratio [aHR]=4.36; 95% CI=2.675-7.103), violation of the inferior superior nasal temporal neuroretinal rim thickness rule (aHR=1.86; 95% CI=1.057-3.258), presence of retinal arterial sclerosis (aHR=1.63; 95% CI=1.040-2.550), and lower total bilirubin level (aHR=0.58; 95% CI=0.340-0.991) were associated with glaucoma development. This study identified the prevalence of PLC as well as the incidence rate of glaucoma conversion and the risk factors for glaucoma development in PLC eyes. The natural history of PLC may help clinicians to better understand its risk factors and the specific management needs of their patients.

Batch-balanced focal loss: a hybrid solution to class imbalance in deep learning.

To validate the effectiveness of an approach called batch-balanced focal loss (BBFL) in enhancing convolutional neural network (CNN) classification performance on imbalanced datasets. BBFL combines two strategies to tackle class imbalance: (1)batch-balancing to equalize model learning of class samples and (2) focal loss to add hard-sample importance to the learning gradient. BBFL was validated on two imbalanced fundus image datasets: a binary retinal nerve fiber layer defect (RNFLD) dataset () and a multiclass glaucoma dataset (). BBFL was compared to several imbalanced learning techniques, including random oversampling (ROS), cost-sensitive learning, and thresholding, based on three state-of-the-art CNNs. Accuracy, F1-score, and the area under the receiver operator characteristic curve (AUC) were used as the performance metrics for binary classification. Mean accuracy and mean F1-score were used for multiclass classification. Confusion matrices, t-distributed neighbor embedding plots, and GradCAM were used for the visual assessment of performance. In binary classification of RNFLD, BBFL with InceptionV3 (93.0% accuracy, 84.7% F1, 0.971 AUC) outperformed ROS (92.6% accuracy, 83.7% F1, 0.964 AUC), cost-sensitive learning (92.5% accuracy, 83.8% F1, 0.962 AUC), and thresholding (91.9% accuracy, 83.0% F1, 0.962 AUC) and others. In multiclass classification of glaucoma, BBFL with MobileNetV2 (79.7% accuracy, 69.6% average F1 score) outperformed ROS (76.8% accuracy, 64.7% F1), cost-sensitive learning (78.3% accuracy, 67.8.8% F1), and random undersampling (76.5% accuracy, 66.5% F1). The BBFL-based learning method can improve the performance of a CNN model in both binary and multiclass disease classification when the data are imbalanced.

Factors Associated with Vascular Changes at the Level of Retinal Ganglion Cell Axon versus Soma/Dendrite in Glaucoma Patients.

Superficial and deep macular vessel density (VD) is decreased in eyes with glaucoma. Superficial VD comprises both the retinal nerve fiber layer (RNFL) and ganglion cell/inner plexiform layer (GC/IPL), and various terms have been used previously to describe the layers of macular VD. In our study, we readjusted the macular segmentation. We obtained RNFL and GC/IPL VDs separately to evaluate VD changes of axon versus soma/dendrite of the retinal ganglion cells (RGCs) in detail. We included 66 eyes of normal tension glaucoma patients with inferior localized RNFL defects solely impacting the inferior hemiretina. Macular VD was measured as RNFL VD and GC/IPL VD. VD ratio was calculated by dividing the VD from the affected hemiretina by the VD from the unaffected hemiretina. RNFL VD ratio was related to RNFL and GC/IPL thicknesses (p = 0.005, p = 0.001), whereas GC/IPL VD ratio was not (p = 0.596, p = 0.783). A lower GC/IPL VD ratio was associated with lower RNFL VD (p = 0.017) and systemic hypertension (p = 0.03) in multivariate analysis. Patients with a reduced GC/IPL VD ratio were more prone to poor visual field defects (p = 0.022) and paracentral scotoma (p = 0.046) and more likely to be on treatment for systemic hypertension (p = 0.024). Therefore, glaucoma patients on systemic hypertension treatment and reduced GC/IPL VD require cautious management.

Retinal Nerve Fiber Layer Optical Texture Analysis: Detecting Axonal Fiber Bundle Defects in Patients with Ocular Hypertension

To apply retinal nerve fiber layer (RNFL) optical texture analysis (ROTA) to investigate the prevalence, patterns, and risk factors of RNFL defects in patients with ocular hypertension (OHT) who showed normal optic disc and RNFL configuration in clinical examination, normal RNFL thickness on OCT analysis, and normal visual field (VF) results. Cross-sectional study. Six hundred eyes of 306 patients with OHT. All participants underwent clinical examination of the optic disc and RNFL, OCT RNFL imaging, and 24-2 standard automated perimetry. To detect RNFL defects, ROTA was applied. The risk score for glaucoma development was calculated according to the Ocular Hypertension Treatment Study and European Glaucoma Prevention Study (OHTS-EGPS) risk prediction model. Risk factors associated with RNFL defects were analyzed using multilevel logistic regression analysis. Prevalence of RNFL defects. The average intraocular pressure (IOP) measured from 3 separate visits within 6 months was 24.9 ± 1.8 mmHg for the eye with higher IOP and 23.7 ± 1.7 mmHg for the eye with lower IOP; the respective central corneal thicknesses were 568.7 ± 30.8 μm and 568.8 ± 31.2 μm. Of 306 patients with OHT, 10.8% (33 patients, 37 eyes) demonstrated RNFL defects in ROTA in at least 1 eye. Of the 37 eyes with RNFL defects, the superior arcuate bundle was the most frequently involved (62.2%), followed by the superior papillomacular bundle (27.0%) and the inferior papillomacular bundle (21.6%). Papillofoveal bundle defects were observed in 10.8% of eyes. The smallest RNFL defect spanned 0.0° along Bruch's membrane opening margin, whereas the widest RNFL defect extended over 29.3°. Age (years) (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.03-1.13), VF pattern standard deviation (decibels [dB]) (OR, 1.82; 95% CI, 1.01-3.29), cup volume (mm3) (OR, 1.24; 95% CI, 1.01-1.53), and the OHTS-EPGS risk score (OR, 1.04; 95% CI, 1.01-1.07) were associated with RNFL defects. A considerable proportion of patients with OHT who showed no signs of optic disc and RNFL thickness abnormalities on clinical and OCT examination exhibited RNFL defects on ROTA. Axonal fiber bundle defects on ROTA may represent the earliest discernible sign of glaucoma in the glaucoma continuum. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Association between localized retinal nerve fiber layer defects in nonglaucomatous eyes and metabolic syndrome: a propensity score-matched analysis.

We investigated the association between metabolic syndrome and localized retinal nerve fiber layer (RNFL) defects in nonglaucomatous subjects. We examined 20,385 adults who visited the Health Promotion Center of Seoul St. Mary's Hospital between May 2015 and April 2016. After excluding those with known glaucoma or glaucomatous optic discs, subjects with and without localized RNFL defects were 1:5 propensity score matched. Metabolic syndrome components, including central obesity, elevated triglyceride, reduced high-density lipoprotein (HDL) cholesterol, elevated blood pressure (BP), and elevated fasting glucose, were compared between two groups. We performed logistic regression to investigate the association between RNFL defects and each component of metabolic syndrome and the number of metabolic syndrome components. Subjects with RNFL defects showed higher waist-to-hip ratios, systolic BP (SBP) and diastolic BP (DBP), fasting blood glucose, and hemoglobin A1c (HbA1c) levels than did those without RNFL defects both before and after propensity score matching. The number of metabolic syndrome components was significantly greater in those with RNFL defects (1.66±1.35) than in those without (1.27±1.32, P<0.01). In multivariate logistic regression, the odds ratio (OR) of RNFL defects was significantly increased in subjects with central obesity [OR =1.53, 95% confidence interval (CI): 1.11-2.13], elevated BP (OR =1.50, 95% CI: 1.09-2.05), and an elevated fasting glucose level (OR =1.42, 95% CI: 1.03-1.97). An increased number of metabolic syndrome components was associated with a higher risk of RNFL defects. Localized RNFL defects in nonglaucomatous subjects are associated with metabolic syndrome components, including central obesity, elevated BP, and an elevated fasting glucose level, suggesting that comorbid metabolic syndrome should be considered when evaluating subjects with RNFL defects.