Abnormal Retinal Nerve Fiber Layer Research Articles

Refining glaucoma diagnosis and treatment in cataract surgery candidates: contribution of preoperative OCT retinal nerve fiber layer.

To evaluate the clinical significance of preoperative spectral domain optical coherence tomography (OCT) of the retinal nerve fiber layer (RNFL) thickness in identifying glaucoma and better managing patients scheduled for routine cataract surgery. Department of Ophthalmology, Shaare Zedek Medical Center, Jerusalem, Israel. Retrospective cohort study. Consecutive patients scheduled for cataract surgery were enrolled from February 2022 to August 2022. Participants underwent routine OCT RNFL studies which were evaluated by a glaucoma specialist. Findings were compared with those of preoperative fundus biomicroscopic examinations conducted by the referring ophthalmologist. The main outcomes were the incidence of newly detected glaucoma based on OCT RNFL findings and the consequent changes in patient management. In total, 486 patients met the inclusion criteria of whom 112 (23%) had abnormal RNFL. 31 patients (6.4%) had abnormal OCT RNFL findings attributed to comorbidities other than glaucoma, and 81 patients (16.7%) were suspected to have glaucoma based on their OCT RNFL findings, from which 44 patients (9%) were newly diagnosed with glaucoma or as glaucoma suspects, resulting in management modifications that included routine glaucoma follow-up (25 patients, 5.1%), initiation of intraocular pressure-lowering treatment (12 patients, 2.5%), and conversion to combined cataract-glaucoma surgery (7 patients, 1.4%). OCT RNFL for cataract surgery candidates proved valuable in detecting glaucoma that had not been revealed by standard fundus biomicroscopic examination. The additional information provided by OCT RNFL can potentially enhance patient management and optimize outcomes.

The Use of Optical Coherence Tomography for Early Glaucoma Screening in a Population of Patients with Diabetes

ABSTRACT Purpose The utility of screening for early diagnosis of glaucoma remains a widely debated topic in the care of ophthalmic patients. There are currently no population-based guidelines regarding screening for glaucoma. The purpose of this study is to determine the utility of optical coherence tomography (OCT) for early glaucoma screening in a population of diabetic patients. The results of this study may inform future screening practices. Methods The current study is a post hoc analysis of OCT data collected from diabetic patients screened for eye disease over 6 months. Glaucoma suspects (GS) were identified based on abnormal retinal nerve fiber layer (RNFL) thickness on OCT. Fundus photographs of GS were graded by two independent raters for vertical cup-to-disc ratio (CDR) and other signs of glaucomatous changes. Results Of the 807 subjects screened, 50 patients (6.2%) were identified as GS. The mean RNFL thickness for GS was significantly lower than the mean RNFL in the total screening population (p < .001). Median CDR for GS was 0.44. Twenty-eight eyes of 17 GS were marked as having optic disc notching or rim thinning by at least one grader. Cohen’s kappa statistic for inter-rater reliability was 0.85. Racial differences showed that mean CDR was significantly higher in non-whites (p < .001). Older age was associated with thinner RNFL (r = −0.29, p = .004). Conclusions Results of this study suggest that in a sample of diabetic patients, a small but clinically significant minority may be flagged as GS based on OCT. Nearly one-third of GS eyes were found to have glaucomatous changes on fundus photography by at least one grader. These results suggest screening with OCT may be useful in detecting early glaucomatous changes in high-risk populations, particularly older, non-white patients with diabetes.

Refractive status and retinal morphology in children with a history of intravitreal ranibizumab for retinopathy of prematurity.

This study investigated the characteristics of refractive status, visual acuity, and retinal morphology in children with a history of receiving intravitreal ranibizumab for retinopathy of prematurity (ROP). Children 4-6years of age were enrolled and divided into the following four groups: group 1, children with a history of ROP who had been treated with intravitreal ranibizumab; group 2, children with a history of ROP who had not received any treatment; group 3, premature children without ROP; and group 4, full-term children. Refractive status, peripapillary retinal nerve fiber layer (RNFL), and macular thickness were measured. A total of 204 children were enrolled. In group 1, myopic shift was not noted, but poorer best corrected visual acuity (BCVA) and shorter axial length were observed. Significantly lower peripapillary RNFL thickness in the average total and superior quadrant, higher central subfield thickness, lower parafoveal retinal thickness in average total, superior, and nasal and temporal quadrants were observed in group 1 than in the other groups. The poor BCVA in patients with ROP was correlated with the lower RNFL thickness in the superior quadrant. Conclusion: Children with a history of type 1 ROP treated with ranibizumab did not show a myopic shift but did show abnormal retinal morphology and the poorest BCVA among all groups. We suggest that pediatric ophthalmologists should always pay attention to visual development in patients with ROP with a history of intravitreal ranibizumab. What is Known: • Anti-VEGF is efficiently and widely used in the treatment of type 1 retinopathy of prematurity (ROP), and different anti-VEGF agents are associated with different prevalence of myopia. • Patients with ROP who receive treatment such as laser therapy or cryotherapy have abnormal macular development and retinal nerve fiber layer (RNFL) thickness. What is New: • Children with a history of ROP treated with intravitreal ranibizumab did not show a myopic shift but did show poor BCVA at 4-6years of age. • Abnormal macular morphology and lower peripapillary RNFL thickness were found in these children.

Thinning of the Lamina Cribrosa and Deep Layer Microvascular Drop Out in Patients with open angle glaucoma and High Myopia.

Lamina cribrosa thinning (thickness of ≤128.00µm) helps to distinguish open angle glaucoma from high myopia, which was associated with the presence of microvasculature dropout and elevated intraocular pressure. To analyze the factors associated with lamina cribrosa (LC) thickness in highly myopic eyes with and without open-angle glaucoma. In total, 240 highly myopic eyes with γ-zones (194 eyes without and 46 eyes with open-angle glaucoma) were examined, and the lamina cribrosa center, externally oblique border, an abrupt change of scleral curvature (scleral step), deep-layer microvasculature dropout and global retinal nerve fiber layer thickness were investigated on optical coherence tomography and optical coherence tomography angiography. Lamina cribrosa were thinner in highly myopic open-angle glaucoma compared with high myopia alone (107.76±9.86 µm VS 137.07±18.51 µm, P<0.001), which was associated with deep-layer microvasculature dropout and elevated intraocular pressure. The areas under the receiver operating characteristic curve for detecting open-angle glaucoma from the lamina cribrosa thickness was 0.964, which was statistically higher (P<0.05) than from the global retinal nerve fiber layer thickness (0.921) and vertical cup-to-disc ratio (0.902). A lamina cribrosa thickness cut-off value of 128 µm provided 100% sensitivity for detecting open-angle glaucoma with 84% specificity. Highly myopic eyes with open-angle glaucoma appear to have a thinner lamina cribrosa, which was associated with elevated intraocular pressure and deep-layer microvasculature dropout. lamina cribrosa thinning (≤128.00 µm) helps distinguish open-angle glaucoma from high myopia with an abnormal retinal nerve fiber layer thickness distribution and unclear shallow disc cupping.

Structure–function assessment in glaucoma based on perimetric sensitivity and en face optical coherence tomography images of retinal nerve fiber bundles

Many studies have assessed structure–function relations in glaucoma, but most without topographical comparison across the central 30°. We present a method for assessing structure–function relations with en face images of retinal nerve fiber layer (RNFL) bundles allowing topographical comparison across much of this retinal area. Forty-four patients with glaucoma (median age 61 years) were recruited and tested with Optical Coherence Tomography (OCT) and perimetry. Six rectangular volume scans were gathered, and then montaged to provide en face views of the RNFL bundles. We calculated the proportion of locations showing a perimetric defect that also showed an en face RNFL defect; and the proportion of locations falling on an RNFL defect that also showed a perimetric defect. A perimetric defect for a location was defined as a total deviation (TD) value equal to or deeper than -4 dB. We found that the median (IQR) number of locations with abnormal RNFL bundle reflectance that also had abnormal TD was 78% (60%) and for locations with abnormal TD that also had abnormal RNFL bundle reflectance was 75% (44%). We demonstrated a potential approach for structure–function assessment in glaucoma by presenting a topographic reflectance map, confirming results of previous studies and including larger retinal regions.

Health-related quality of life determinants in survivors of a mass methanol poisoning outbreak: six-year prospective cohort study

Purpose: The effect of acute methanol poisoning on the follow-up quality of life of survivors in mass poisoning outbreaks is not known. The objective of this is to study the impact of visual and central nervous system (CNS) sequelae of methanol poisoning on long-term health-related quality of life (QoL) of survivors, its clinical determinants, and dynamics.Materials and methods: A total of 54 patients with confirmed methanol poisoning (mean age 46.7 ± 13.4 years, 9 females) were examined consequently three times within six-year prospective cohort study and compared to 23 controls with the history of chronic alcohol abuse. The following tests were performed: SF-36 QoL questionnaire, visual evoked potentials (VEP) of optic nerve, ocular examination with retinal nerve fiber layer (RNFL) thickness measurement, brain magnetic resonance imaging (MRI), and biochemical and toxicological tests.Results: Acute methanol poisoning led to significant decrease in physical component summary (PCS) compared to PCS of age-adjusted controls (mean score with SD 46.8 ± 11.0 versus 52.3 ± 9.4 points; p = .003). In 17/40 (42.5%) patients with three rounds of examination, signs of severe disability (≤30 points in at least one score) were present six years after discharge, with negative dynamics of PCS score during the observation period. The patients with abnormal RNFL thickness had lower PCS (mean difference 10.5 points; 95%CI 3.5–17.5, p = .004) and mental component summary score (9.5 points; 95%CI 1.9–17.1, p = .015) compared to the patients with normal RNFL. Signs of physical and mental adaptation to long-term visual sequelae were registered with gradual reduction of difference in most of physical and mental components scores compared to the patients with normal RNFL during six years of observation. Signs of hemorrhagic brain lesions were associated with permanent decrease of PCS score (mean difference 7.4 points; 95%CI 0.6–14.0; p = .033), bodily pain (8.7 points; 95%CI 1.6–17.6; p = .018), and social functioning (8.2 points; 95%CI 3.0–17.4; p = .005) six years after discharge. No effect of type of antidote (fomepizole versus ethanol) and extracorporeal enhanced elimination modality (intermittent hemodialysis versus continuous renal replacement therapy) applied in hospital on long-term QoL was found (all p > .05).Conclusion: Acute methanol poisoning was associated with a significant decrease of health-related quality of life of survivors persisting for at least six years after discharge. The more pronounced decrease in QoL scores was observed in the patients with hemorrhagic brain lesions and visual sequelae of poisoning with abnormal RNFL thickness.

Characteristics of Patients Showing Discrepancy Between Bruch's Membrane Opening-Minimum Rim Width and Peripapillary Retinal Nerve Fiber Layer Thickness.

Background: To investigate clinical characteristics of patients showing discrepancy between Bruch’s membrane opening minimum rim width (BMO-MRW) and peripapillary retinal nerve fiber layer (RNFL) thickness. Correlation with the visual field (VF) was also inspected. Methods: In this prospective, cross-sectional study, 106 eyes (106 subjects) showing normal BMO-MRW classification but abnormal RNFL classification were included. All patients underwent confocal scanning laser ophthalmoscopy, spectral-domain optical coherence tomography, and standard automated perimetry. Results: Clinical characteristics were as follows: mean age: 52.79 ± 14.75 years; spherical equivalent (SE), −2.52 ± 3.48 diopter (D); SE < −5.0 D, 34 (32.1%) eyes; large disc (>2.43 mm2), 40.6%; small disc (<1.63 mm2), 12.5%; VF index, 96.72 ± 9.58%; mean deviation, −1.74 ± 3.61 dB; β-peripapillary atrophy (PPA), 96.2%; γ-PPA, 75.5%. Majority (86.1%) of these cases demonstrated normal (71.3%) or borderline (14.9%) on VF. Temporal and nasal RNFL showed significant differences among disc size subgroups (all p < 0.05). Nasal RNFL was significantly thicker in a large disc group than other subgroups. Temporal, superotemporal, inferotemporal, inferonasal RNFL, and superior RNFL peak location showed significant differences (all p < 0.05) among SE subgroups. Temporal RNFL was significantly thicker in the high myopia group than other subgroups. Conclusions: Temporalization of RNFL peaks in myopia and nasalization of RNFL peaks in large disc that display abnormal classifications might show normal classification of BMO-MRW. These findings of discrepancy between classifications should be considered in the diagnosis of early glaucoma.

Retinal Nerve Fiber Layer Thinning Is Associated With Brain Atrophy: A Longitudinal Study in Nondemented Older Adults.

Backgrounds: Abnormal retinal nerve fiber layer (RNFL) thickness has been observed in patients with Alzheimer’s disease (AD) and therefore suggested to be a potential biomarker of AD. However, whether the changes in RNFL thickness are associated with the atrophy of brain structure volumes remains unknown. We, therefore, set out a prospective investigation to determine the association between longitudinal changes of RNFL thickness and brain atrophy in nondemented older participants over a period of 12 months.Materials and Methods: We measured the RNFL thickness using optical coherence tomography (OCT) and brain structure volumes by 3T magnetic resonance imaging (MRI) before and after 12 months. Cognitive function was assessed using the Chinese version of Mini-Mental State Examination (CMMSE) and Repeatable Battery for the Assessment of Neurological Status. Associations among the changes of RNFL, brain structures and cognitive function were analyzed with Spearman correlation and multiple linear regression models adjusting for the confounding factors.Results: Fifty old participants were screened and 40 participants (mean age 71.8 ± 3.9 years, 60% were male) were enrolled at baseline. Among them, 28 participants completed the follow-up assessments. The average reduction of RNFL thickness was inversely associated with the decrease of central cingulate cortex volume after the adjustment of age and total intracranial volume (β = −0.41, P = 0.039). Specifically, the reduction of RNFL thickness in the inferior, not other quadrants, was independently associated with the decline of central cingulate cortex volume after the adjustment (β = −0.52, P = 0.006). Moreover, RNFL thinning, central cingulate cortex atrophy and the aggregation of white matter hyperintensities (WMH) were found associated with episodic memory in these older adults with normal cognition.Conclusions: RNFL thinning was associated with cingulate cortex atrophy and episodic memory decline in old participants. The longitudinal changes of RNFL thickness are suggested to be a useful complementary index of neurocognitive aging or neurodegeneration.

Development of Topographic Scoring System for Identifying Glaucoma in Myopic Eyes: A Spectral-Domain OCT Study

To develop a new scoring system that uses topographic diagnostic signs of spectral-domain (SD) OCT to enhance glaucoma diagnostic performance for myopic eyes and to validate the system's diagnostic ability. Cross-sectional study. A total of 517 patients (517 eyes; spherical equivalent [SE] <-1.0 diopters [D] or axial length >24.0 mm), including 175 highly myopic eyes (SE <-6.0 D or axial length >26.0 mm), were recruited and divided into 2, training (241 eyes) and validation (276 eyes) test sets. Retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) topographic signs were selected based on the morphologic patterns of RNFL (size, shape, location, and agreement between deviation and thickness maps) and GCIPL (size, shape, location, color tone, agreement between maps, and step sign) abnormalities indicative of higher likelihood of myopic glaucoma on deviation and thickness maps. The diagnostic score was compiled according to the sensitivity, specificity, and positive likelihood ratio (PLR) of each diagnostic sign using the training set. The area under the receiver operating characteristic curve (AUC) was plotted and compared between the OCT-provided parameters and the scoring system in the validation set. The diagnostic performance of a new scoring system as validated by AUC. Among all of the RNFL and GCIPL parameters, the presence of temporal hemifield asymmetry on the GCIPL thickness map (PLR, 5.98) showed the highest diagnostic ability, followed by location of the RNFL defect (PLR, 5.79) and color tone of the GCIPL defect (PLR, 5.04). The AUC of the topographic scoring system in myopic eyes was 0.979, which was significantly higher than those of the inferior (0.895; P < 0.001) and average (0.894; P < 0.001) RNFL thickness parameters. For highly myopic eyes, the scoring system (AUC, 0.983) also showed a higher diagnostic performance than that of the RNFL and GCIPL thickness parameters (all P < 0.001). Our scoring system including OCT topographic parameters demonstrated to be beneficial for clinicians to differentiate real glaucomatous damage from myopic healthy eyes. Our results support the value of using multitopographic OCT parameters for detecting glaucoma in myopic eyes.

Preoperative spectral-domain optical coherence tomography in patients having cataract surgery

To evaluate the role and cost-effectiveness of preoperative spectral-domain optical coherence tomography (SD-OCT) in patients having cataract surgery. Fondation Opthalmologique Adolphe de Rothschild, Paris, France. Retrospective case series. All patients who had cataract surgery had macular and retinal nerve fiber layer SD-OCT preoperatively. A complete ophthalmologic examination was performed, including corrected near (CNVA) and corrected distance visual acuities, intraocular pressure (IOP), and a fundus examination. The study comprised 245 patients (401 eyes) with amean age of 73.5years±9.81 and a mean IOP of 15.6±3.04mm Hg. Of 107 eyes (26.7%) with abnormal macular SD-OCT, 70 eyes were judged normal on fundus examination. The most frequent anomalies were age-related macular degeneration and epiretinal membrane. Age over 70years and CNVA worse than Parinaud 2 were associated with higher rate of abnormal macular SD-OCT (odds ratio, 2.76 and 2.28, respectively). Fifty-seven eyes (14.2%) had abnormal retinal nerve fiber layer SD-OCT, 30% of them with no history of glaucoma and no detected anomaly on fundus examination. Age over 70years and a history of glaucoma were associated with a higher rate of retinal nerve fiber layer anomalies. Preoperative SD-OCT scanning was significantly more effective in detecting anomalies in patients having cataract surgery than fundus examination. Older age and CNVA worse than Parinaud 2 were associated with higher rates of abnormal macular SD-OCT. Older age and a history of glaucoma were associated with higher abnormal retinal nerve fiber layer anomaly rates.

Glaucoma suspects: A practical approach.

Glaucoma suspects are controversial clinical dilemmas. These individuals harbor certain risk factors or demonstrate some clinical features suggestive of an increased probability to develop glaucomatous optic atrophy in the future. These characteristics range from high intraocular pressure; optic disc, visual field, or retinal nerve fiber layer abnormalities; or abnormal angles to a positive family history of glaucoma and other risk factors. Individuals having these characteristics should be assessed diligently before a diagnosis of glaucoma is made. Glaucoma is a chronic, lifelong condition, having a negative impact on the quality of life, with an increased risk of medication-related side-effects, adverse economic impacts, and the need for lifestyle changes in the patient. Overdiagnosis and unnecessary treatment of such individuals is bereft of any advantage. This review aims to provide a practical blueprint for the proper diagnosis and management of such glaucoma suspects.

Optical Coherence Tomography in the Management of Skull Base Fibrous Dysplasia with Optic Nerve Involvement.

Fibrous dysplasia (FD) of the skull base can manifest with optic nerve compression. As most patients initially do not experience vision loss, controversy exists whether to proceed with prophylactic surgical decompression or elect for conservative observation. Optical coherence tomography (OCT), a physiologic imaging modality widely used to assess the condition of the retinal nerve fiber layer (RNFL), has been useful in monitoring compressive tumors on the optic nerve. This study evaluated potential use of OCT in management of patients with fibrous dysplasia and optic nerve involvement. Six patients with suspected optic nerve compression who underwent OCT imaging as part of a neuro-ophthalmic examination were reviewed over a 2-year period. Patient records were evaluated for visual examination measures, most notably the presence of optic neuropathy, and radiographic measures on computed tomography. Measures were compared by age-adjusted RNFL thickness (above or below fifth percentile) on OCT imaging. Two patients were found to have mild optic neuropathy in 1 eye each. Three of 12 eyes fell below the age-adjusted fifth percentile of RNFL thickness. Presence of optic neuropathy was associated with abnormal age-adjusted RNFL thickness but not with optic nerve compression (P= 0.45). Abnormal RNFL thickness as measured by OCT better predicted the presence of optic neuropathy than computed tomography alone. OCT may be a valuable imaging modality to monitor patients with fibrous dysplasia for development of optic neuropathy during periods of conservative watchful waiting.

Factors Associated with the Retinal Nerve Fiber Layer Loss after Acute Primary Angle Closure: A Prospective EDI-OCT Study.

PurposeTo determine the factors associated with retinal nerve fiber layer (RNFL) loss in eyes with acute primary angle-closure (APAC), particularly focusing on the influence of the change in the anterior lamina cribrosa surface depth (LCD).MethodsAfter the initial presentation, 30 eyes with unilateral APAC were followed up at the following specific time points over a 12-month period: 1 week, 1~2 months, 2~3 months, 5~6 months, and 11~12 months. These follow-ups involved intraocular pressure measurements, enhanced depth-imaging spectral-domain optical coherence tomography (SD-OCT) scanning of the optic disc, and measurements of the circumpapillary RNFL thickness. The prelaminar tissue thickness (PLT) and LCD were determined in the SD-OCT images obtained at each follow-up visit.ResultsRepeated measures analysis of variance revealed a significant pattern of decrease in the global RNFL thickness, PLT, and LCD (all p<0.001). The global RNFL thickness decreased continuously throughout the follow-up period, while the PLT decreased until 5~6 months and did not change thereafter. The LCD reduced until 2~3 months and then also remained steady. Multivariable regression analysis revealed that symptoms with a longer duration before receiving laser peripheral iridotomy (LI) (p = 0.049) and a larger LCD reduction (p = 0.034) were significant factors associated with the conversion to an abnormal RNFL thickness defined using OCT normative data.ConclusionEarly short-term decreases in the PLT and LCD and overall long-term decrease in the peripapillary RNFL were observed during a 12-month follow-up after an APAC episode. A longer duration of symptoms before receiving LI treatment and larger LCD reduction during follow-up were associated with the progressive RNFL loss. The LCD reduction may indicate a prior presence of significant pressure-induced stress that had been imposed on the optic nerve head at the time of APAC episode. Glaucomatous progression should be suspected in eyes showing LCD reduction after the APAC remission.

Risk factors for visual field progression of normal-tension glaucoma in patients with myopia

ObjectiveTo identify risk factors for visual field progression of normal-tension glaucoma (NTG) in patients with myopia. DesignLongitudinal, observational study. ParticipantsFifty-one eyes of 51 NTG patients with myopia (less than −0.75D based on spherical equivalence) who had undergone visual field (VF) testing at least once per year for ≥6 years between November 2005 and December 2013. MethodsProgression was defined using event-based guided progression analysis. Risk factors were analyzed using the Cox proportional hazards model and further tested for independence in a multivariate model. ResultsThe mean observation period was 7.0 ± 1.3 years, and 16 of 51 subjects showed progression. In the univariate analysis, abnormal retinal nerve fibre layer (RNFL) colour codes (yellow or red sector) at the 11, 10, and 7 o’clock positions on optical coherence tomography showed significant associations with the VF progression (p = 0.03, 0.03, and 0.01, respectively). In the final multivariate models, the abnormal RNFL colour code of the 7 o’clock sector (inferotemporal sector) was the only significant risk factor for progression (hazard ratio = 4.07 and 4.37; 95% CI, 1.11–14.92 and 1.27–15.04; p = 0.03 and 0.02, respectively). ConclusionsInferotemporal RNFL thinning could be a risk factor for progression in NTG patients with myopia.

Evaluation of a Myopic Normative Database for Analysis of Retinal Nerve Fiber Layer Thickness.

Analysis of retinal nerve fiber layer (RNFL) abnormalities with optical coherence tomography in eyes with high myopia has been complicated by high rates of false-positive errors. An understanding of whether the application of a myopic normative database can improve the specificity for detection of RNFL abnormalities in eyes with high myopia is relevant. To evaluate the diagnostic performance of a myopic normative database for detection of RNFL abnormalities in eyes with high myopia (spherical equivalent, -6.0 diopters [D] or less). In this cross-sectional study, 180 eyes with high myopia (mean [SD] spherical equivalent, -8.0 [1.8] D) from 180 healthy individuals were included in the myopic normative database. Another 46 eyes with high myopia from healthy individuals (mean [SD] spherical equivalent, -8.1 [1.8] D) and 74 eyes from patients with high myopia and glaucoma (mean [SD] spherical equivalent, -8.3 [1.9] D) were included for evaluation of specificity and sensitivity. The 95th and 99th percentiles of the mean and clock-hour circumpapillary RNFL thicknesses and the individual superpixel thicknesses of the RNFL thickness map measured by spectral-domain optical coherence tomography were calculated from the 180 eyes with high myopia. Participants were recruited from January 2, 2013, to December 30, 2015. The following 6 criteria of RNFL abnormalities were examined: (1) mean circumpapillary RNFL thickness below the lower 95th or (2) the lower 99th percentile; (3) one clock-hour or more for RNFL thickness below the lower 95th or (4) the lower 99th percentile; and (5) twenty contiguous superpixels or more of RNFL thickness in the RNFL thickness map below the lower 95th or (6) the lower 99th percentile. Specificities and sensitivities for detection of RNFL abnormalities. Of the 46 healthy eyes and 74 eyes with glaucoma studied (from 39 men and 38 women), the myopic normative database showed a higher specificity (63.0%-100%) than did the built-in normative database of the optical coherence tomography instrument (8.7%-87.0%) for detection of RNFL abnormalities across all the criteria examined (differences in specificities between 13.0% [95% CI, 1.1%-24.9%; P = .01] and 54.3% [95% CI, 37.8%-70.9%; P < .001]) except for the criterion of mean RNFL thickness below the lower 99th percentile, in which both normative databases had the same specificities (100%) but the myopic normative database exhibited a higher sensitivity (71.6% vs 86.5%; difference in sensitivities, 14.9% [95% CI, 4.6%-25.1%; P = .002]). The application of a myopic normative database improved the specificity without compromising the sensitivity compared with the optical coherence tomography instrument's built-in normative database for detection of RNFL abnormalities in eyes with high myopia. Inclusion of myopic normative databases should be considered in optical coherence tomography instruments.

Prevalence of Glaucoma in Myopic Corneal Refractive Surgery Candidates in Hong Kong China.

To estimate the prevalence of glaucoma in myopic individuals in Hong Kong China seeking corneal refractive surgery and factors associated with the occurrence of glaucoma. Six hundred twenty-nine eyes of 315 myopic individuals seeking corneal refractive surgery in a tertiary institution in Hong Kong China, were consecutively recruited. Glaucoma was defined by the presence of abnormal retinal nerve fiber layer (RNFL) and neuroretinal rim measurements obtained with spectral-domain optical coherence tomography, as well as narrowed neuroretinal rim and optic disc excavation observed in color optic disc stereophotographs. Factors associated with glaucoma were analyzed with univariable and multivariable mixed-effects logistic regression analysis. The mean age and spherical equivalent were 36.3 ± 9.3 years (range: 21.5 to 60.1 years) and -6.59 ± 2.34 diopters (D) (range: -2.25 to -17.13 D), respectively. Twenty-three eyes of 16 myopic individuals (5.1%; 95% confidence interval [CI]: 3.2% to 8.1%) had glaucoma, of which 10 eyes of 7 myopic individuals (2.2%; 95% CI: 1.1% to 4.5%) also had visual field defects by standard automated perimetry (5 had mild and 5 had moderate visual field loss). None of the myopic individuals were aware of the diagnosis at the time of examination. The inferotemporal sector of the optic disc was the most frequent location where RNFL thinning was found and the superonasal visual field was the most common region where visual field defects were located. The only biometric factor associated with glaucoma was intraocular pressure (odds ratio: 1.77; 95% CI: 1.14 to 2.75). Glaucoma was present in 5.1% of myopic individuals seeking corneal refractive surgery in Hong Kong China. Corneal refractive surgeons should be watchful in the diagnostic evaluation of glaucoma among myopic corneal refractive surgery candidates. [J Refract Surg. 2016;32(5):298-304.].

Estimating Lead Time Gained by Optical Coherence Tomography in Detecting Glaucoma before Development of Visual Field Defects

To estimate the diagnostic accuracy and lead time gained by retinal nerve fiber layer (RNFL) thickness measurements from optical coherence tomography (OCT) for detecting glaucoma before the development of visual field defects. Observational cohort study. The study group included 75 eyes of 75 patients suspected of having glaucoma. These eyes had normal standard automated perimetry (SAP) at baseline and demonstrated repeatable (3 consecutive) abnormal tests during a median follow-up of 6.3 years. A control group of 75 eyes of 75 healthy subjects matched by age and number of OCT tests during follow-up was included. The RNFL thickness measurements were obtained at the time of development of the earliest SAP defect (time 0) and also at times -1, -2, -3, and so forth, corresponding to 1 year, 2 years, 3 years, and so forth, before the development of field loss. The OCT measurements at corresponding intervals were analyzed for controls. Time-dependent receiver operating characteristic (ROC) curves were used to evaluate diagnostic accuracy of OCT. Areas and sensitivities of ROC curve at fixed specificities at different times before development of field loss. At the date of conversion to the earliest visual field defect (time 0), mean ± standard deviation average RNFL thickness was 75.0±9.8 μm in glaucomatous eyes and 90.6±8.0 μm for controls (P < 0.001). Significant differences were seen up to 8 years before development of visual field defects (86.3±8.2 μm vs. 91.4±7.6 μm, respectively; P = 0.021). The ROC curve areas decreased with increasing times before detection of field defects. At times 0, -4, and -8 years, ROC curve areas were 0.87, 0.77, and 0.65, respectively. At 95% specificity, up to 35% of eyes had abnormal average RNFL thickness 4 years before development of visual field loss and 19% of eyes had abnormal results 8 years before field loss. Assessment of RNFL thickness with OCT was able to detect glaucomatous damage before the appearance of visual field defects on SAP. In many subjects, significantly large lead times were seen when applying OCT as an ancillary diagnostic tool.

Intereye Comparison of Cirrus OCT in Early Glaucoma Diagnosis and Detecting Photographic Retinal Nerve Fiber Layer Abnormalities.

To compare the ability of various maps constructed using Cirrus optical coherence tomography (OCT), including the "intereye comparison" derived from the temporal superior inferior nasal temporal (TSNIT) map, in terms of glaucoma diagnosis and detection of RNFL defects identified in red-free fundus photographs. This cross-sectional study was conducted on a total of 131 open-angle glaucoma patients with early-stage visual field defects (mean deviation ≤ -6.0 dB) and 56 healthy controls. Intereye differences were identified on TSNIT maps constructed by comparing the RNFL thickness curves of both eyes of individual patients and a separation of the RNFL thickness curves of either eye (by >50 μm) was defined as an abnormality. Among 131 red-free fundus photographic RNFL defects, 57 (44.0%) in the Clock-hour map, 51 (39.0%) in the Quadrant map, 37 (28%) in the Deviation map, 16 (12%) in the Thickness map, and 3 (2%) in the intereye difference obtained from the TSNIT map were misidentified. The intereye difference derived from the TSNIT map afforded a sensitivity superior to that of all other maps when used to evaluate eyes with glaucoma (98.0%, all P values < 0.05), and preperimetric eyes (97.7%, all P values < 0.001). Of the various maps constructed by the Cirrus OCT, comparison of the RNFL thickness curves of both eyes of an individual, which was possible using TSNIT map data, afforded the best diagnostic capability in terms of detecting photographic RNFL defects. Intereye comparisons of TSNIT thickness curves may be useful to detect early-stage glaucoma.

Population-based evaluation of retinal nerve fiber layer, retinal ganglion cell layer, and inner plexiform layer as a diagnostic tool for glaucoma.

We determined the glaucoma screening performance of regional optical coherence tomography (OCT) layer thickness measurements in the peripapillary and macular region, in a population-based setting. Subjects (n = 1224) in the Rotterdam Study underwent visual field testing (Humphrey Field Analyzer) and OCT of the macula and optic nerve head (Topcon 3-D OCT-1000). We determined the mean thicknesses of the retinal nerve fiber layer (RNFL), retinal ganglion cell layer (RGCL), and inner plexiform layer for regions-of-interest; thus, defining a series of OCT parameters, using the Iowa Reference Algorithms. Reference standard was the presence of glaucomatous visual field loss (GVFL); controls were subjects without GVFL, an intraocular pressure (IOP) of 21 mm Hg or less, and no positive family history for glaucoma. We calculated the area under the receiver operating characteristics curve (AUCs) and the sensitivity at 97.5% specificity for each parameter. After excluding 23 subjects with an IOP > 21 mm Hg and 73 subjects with a positive family history for glaucoma, there were 1087 controls and 41 glaucoma cases. Mean RGCL thickness in the inferior half of the macular region showed the highest AUC (0.85; 95% confidence interval [CI] 0.77-0.92) and sensitivity (53.7%; 95% CI, 38.7-68.0%). The mean thickness of the peripapillary RNFL had an AUC of 0.77 (95% CI, 0.69-0.85) and a sensitivity of 24.4% (95% CI, 13.7-39.5%). Macular RGCL loss is at least as common as peripapillary RNFL abnormalities in population-based glaucoma cases. Screening for glaucoma using OCT-derived regional thickness identifies approximately half of those cases of glaucoma as diagnosed by perimetry.

Diagnostic Classification of Macular Ganglion Cell and Retinal Nerve Fiber Layer Analysis: Differentiation of False-Positives from Glaucoma

To investigate the rate and associated factors of false-positive diagnostic classification of ganglion cell analysis (GCA) and retinal nerve fiber layer (RNFL) maps, and characteristic false-positive patterns on optical coherence tomography (OCT) deviation maps. Prospective, cross-sectional study. A total of 104 healthy eyes of 104 normal participants. All participants underwent peripapillary and macular spectral-domain (Cirrus-HD, Carl Zeiss Meditec Inc, Dublin, CA) OCT scans. False-positive diagnostic classification was defined as yellow or red color-coded areas for GCA and RNFL maps. Univariate and multivariate logistic regression analyses were used to determine associated factors. Eyes with abnormal OCT deviation maps were categorized on the basis of the shape and location of abnormal color-coded area. Differences in clinical characteristics among the subgroups were compared. (1) The rate and associated factors of false-positive OCT maps; (2) patterns of false-positive, color-coded areas on the GCA deviation map and associated clinical characteristics. Of the 104 healthy eyes, 42 (40.4%) and 32 (30.8%) showed abnormal diagnostic classifications on any of the GCA and RNFL maps, respectively. Multivariate analysis revealed that false-positive GCA diagnostic classification was associated with longer axial length and larger fovea-disc angle, whereas longer axial length and smaller disc area were associated with abnormal RNFL maps. Eyes with abnormal GCA deviation map were categorized as group A (donut-shaped round area around the inner annulus), group B (island-like isolated area), and group C (diffuse, circular area with an irregular inner margin in either). The axial length showed a significant increasing trend from group A to C (P=0.001), and likewise, the refractive error was more myopic in group C than in groups A (P=0.015) and B (P=0.014). Group C had thinner average ganglion cell-inner plexiform layer thickness compared with other groups (group A=B>C, P=0.004). Abnormal OCT diagnostic classification should be interpreted with caution, especially in eyes with long axial lengths, large fovea-disc angles, and small optic discs. Our findings suggest that the characteristic patterns of OCT deviation map can provide useful clues to distinguish glaucomatous changes from false-positive findings.