Predicting perimetric defects from en face maps of retinal nerve fibre layer reflectance.

PURPOSE: To develop criteria to predict visual hemifields with deep perimetric defects based on retinal nerve fibre layer (RNFL) reflectance, in a transparent process whose components can be assessed by independent laboratories analysing data from their own small groups. METHODS: The analysis was carried out in four stages, using three independent groups of patients-30, 33 and 62 participants-with glaucoma and age-similar controls. The first stage used Group 1 to develop a criterion for RNFL reflectance images at 24, 36 or 48 µm below the inner limiting membrane (ILM). The second stage evaluated the criterion using Group 2. The third stage developed a second criterion to improve performance for Groups 1 and 2 combined. The fourth stage evaluated the second criterion with Group 3. Confidence intervals for sensitivity and specificity were then computed by combining results from all three groups. RESULTS: The first criterion identified all hemifields with deep defects and no hemifields from controls, using a within-eye reference for healthy RNFL. For Group 2, specificity remained high but sensitivity was reduced. The second criterion improved sensitivity by using location-specific reference values. For Group 3, sensitivity remained high but reduced specificity was found. Confidence intervals showed substantial overlap for the two criteria. CONCLUSIONS: We developed two criteria to identify patients with deep perimetric defects with high specificity and sensitivity. Several improvements are warranted: automated identification of the fovea-disc angle and optic disc locations, evaluation of normal variation in patterns of RNFL thickness, improved segmentation of ILM and major vasculature, reduction of within-eye variability in RNFL reflectance of healthy eyes, assessment of effects of image quality, assessment of effects of comorbidity and effectiveness of other devices.

Within-eye and between-subject variability for reflectance of the retinal nerve fibre layer.

PURPOSE: Reflectance of retinal nerve fibre layer (RNFL) can contribute to detecting the presence of glaucomatous damage and defining its extent. As a step towards developing a normative database for RNFL reflectance, we assessed within-eye and between-subject variability for RNFL reflectance in healthy eyes. METHODS: Vertical 30° × 15° volume scans at the optic disc were gathered using SD-OCT (Spectralis OCT) from people free of eye disease. Scans were gathered for both eyes of 30 younger adults (mean ± SD = 27 ± 3 years) and for one eye of 30 older adults (68 ± 8 years). Reflectance was quantified for each voxel as the depth-resolved attenuation coefficient (AC). Values for AC were extracted for four slabs (0-52, 24-52, 24-36 and 36-60 µm) and at depths from 24 to 60 µm below the inner limiting membrane (ILM) in 4 µm steps. RESULTS: Between-subject and within-eye standard deviations (SDs) for the logarithm of AC were similar; median differences were 0.02-0.03 log unit across all four slabs and depths from 24 to 48 µm. Means for the logarithm of AC were higher for younger than older eyes by ~0.1 log unit; this age effect was not due to differences in the raw reflectance of the RNFL, but rather to age-related changes in reflectance of deeper retina affecting the calculation of AC. CONCLUSIONS: In both groups, within-eye variability in RNFL reflectance near the optic disc was similar to between-subject variability. A better understanding of within-eye variability would be useful for developing normative databases.

A Novel Stimulus to Improve Perimetric Sampling within the Macula in Patients with Glaucoma.

SIGNIFICANCE: Identifying glaucomatous damage to the macula has become important for diagnosing and managing patients with glaucoma. In this study, we presented an approach that provides better perimetric sampling for the macular region, by testing four locations, with a good structure-function agreement. PURPOSE: We previously presented a basis for customizing perimetric locations within the macula. In this study, we aimed to improve perimetric sampling within the macula by presenting a stimulus at four locations, with maintaining a good structure-function agreement. METHODS: We tested one eye each of 30 patients (aged 50 to 88 years). Patients were selected based on observed structural damage to the macula, whereas perimetric defect (using 24-2) did not reflect the locations and extent of this damage. We used en face images to visualize retinal nerve fiber bundle defects. To measure perimetric sensitivities, we used a blob stimulus (standard deviation of 0.25°) at the 10-2 locations. A perimetric defect for a location was defined as any value equal to or deeper than -4, -5, and -6 dB below the mean sensitivity for 37 age-similar controls (aged 47 to 78 years). We also presented an elongated sinusoidal stimulus for 20 patients at four locations within the macula, in which we defined a perimetric defect as any value below the 2.5th percentile from controls. RESULTS: The -4, -5, and -6 dB criteria identified perimetric defects in 14, 13, and 11 patients, respectively. When testing with the elongated stimulus, 18 patients were identified with perimetric defect. The perimetric defects were consistent with the structural damage. CONCLUSIONS: The elongated stimulus showed a good structure-function agreement with only four testing locations as compared with 68 locations used with the blob stimulus. This demonstrates a clinical potential for this new stimulus in the next generation of perimetry.

Interpreting Retinal Nerve Fiber Layer Reflectance Defects Based on Presence of Retinal Nerve Fiber Bundles.

SIGNIFICANCE: Adaptive-optics scanning-laser-ophthalmoscopy (AOSLO) retinal imaging of the retinal nerve fiber layer (RNFL) helps predict the severity of perimetric damage based on absence of fibers and projection of the defects in en face images of the RNFL from spectral-domain optical coherence tomography (SD-OCT). PURPOSE: En face images of the RNFL reveal reflectance defects in patients with glaucoma and predict locations of perimetric defects. These defects could arise from either loss of retinal nerve fiber bundles or reduced bundle reflectance. This study used AOSLO to assess presence of bundles in areas with RNFL reflectance defects on SD-OCT. METHODS: Adaptive-optics scanning laser ophthalmoscopy was used to image a vertical strip of RNFL measuring approximately 30 × 3° between the optic disc and the fovea. Fifteen patients with glaucoma who had SD-OCT reflectance defects that passed through this region were chosen. Four patients had reflectance defects in both superior and inferior hemifields, so presence of bundles on AOSLO was assessed for 19 hemifields. Where bundles were present, the hemifield was scored for whether bundles seemed unusual (low contrast and/or low density). Perimetric defects were considered deep when sensitivity was below 15 dB. RESULTS: Ten hemifields had a region with no fibers present on AOSLO; all had a corresponding deep perimetric defect. The other nine hemifields had no region in the AOSLO image without fibers: four with normal fibers and five with unusual fibers. The only one of these nine hemifields with a deep perimetric defect was one with low-contrast fibers and overall thin RNFL. CONCLUSIONS: Retinal nerve fiber layer reflectance defects, which were associated with deep perimetric defects, usually had a region with absence of fibers on AOSLO images of RNFL. Ability to predict severity of perimetric damage from en face SD-OCT RNFL reflectance images could benefit from quantification that differentiated between absence of fibers and unusual fibers.

Functional characteristics of glaucoma related arcuate defects seen on OCT en face visualisation of the retinal nerve fibre layer.

PURPOSE: To assess continuity of perimetric defects corresponding to arcuate defects seen on optical coherence tomography (OCT) en face reflectance images of the retinal nerve fibre layer (RNFL) in patients with glaucoma. METHODS: Seven patients with glaucoma who had arcuate structural defects on OCT RNFL en face images were recruited. Static suprathreshold stimuli were presented along different meridians to localise perimetric defects in the corresponding hemifield. Then two contrasts, one 6 dB greater than the other, were used with kinetic perimetry to assess the slope of the defect. Findings with kinetic and 24-2 perimetry were compared. RESULTS: Static perimetry found that regions of perimetric abnormality spatially corresponded with the regions of en face RNFL hyporeflectivity. Kinetic perimetry found that the slopes of the edges of the defects ranged from 3-12 dB degree-1 , and that the functional abnormalities were continuous with the physiologic blind spot even when the 24-2 protocol only showed paracentral defects. CONCLUSIONS: Perimetric abnormalities and arcuate RNFL en face defects were spatially correspondent. Perimetric testing guided by OCT en face reflectance images can reveal greater functional detail of glaucomatous abnormality than 24-2 testing.

Assessing the Impact of En Face Retinal Nerve Fiber Layer Imaging on Clinical Decision Making for Glaucoma Suspects.

SIGNIFICANCE: Assessing and managing glaucoma are a complicated process in which experience plays a key role in decision making. Although advanced glaucoma is more easily diagnosed, patients with early glaucoma or who present with suspicious findings are more complicated. A need to aid clinicians in the decision-making process exists. PURPOSE: The purpose of this study was to assess the impact of en face ocular coherence tomography images to clinical decision making when added to standard presentations of circumpapillary retinal nerve fiber layer thickness and automated perimetry. METHODS: Thirty participants from two centers presenting either as a glaucoma suspect or for an initial glaucoma evaluation were enrolled. Six masked investigators were given standard presentations of circumpapillary retinal nerve fiber layer thickness and perimetry. They were asked if glaucomatous damage was present as well as a recommended plan of management on 5-point Likert scales. They were then given en face images of the retinal nerve fiber layer in three different presentations coupled with the standard presentation, and the questions were repeated. An intraclass correlation coefficient (ICC) was generated. RESULTS: The masked investigators had moderate agreement from the standard presentation for assessment (ICC = 0.67 [95% confidence interval {CI}, 0.54 to 0.80] and ICC = 0.69 [95% CI, 0.52 to 0.80], respectively), as well as with the addition of the en face images (ICC = 0.69; 95% CI, 0.56 to 0.81). The en face images tended to change decisions in both assessment and plan toward likely to have glaucoma and likely to start treatment. CONCLUSIONS: The addition of en face images to a standard presentation has an impact on clinical decision making. Although en face images seem to influence the decision toward likely to have glaucoma and likely to treat, it is unclear if this leads to a more accurate decision. Further investigations seem warranted to assess sensitivity and specificity of this approach.

Presumed activated retinal astrocytes and Müller cells in healthy and glaucomatous eyes detected by spectral domain optical coherence tomography.

PURPOSE: To investigate presumed activated retinal astrocytes and Müller cells (ARAM) detected by scanning laser ophthalmoscopy (SLO) and spectral domain optical coherence tomography, and to investigate its presence in healthy controls as well as its relationship to posterior vitreal detachment (PVD) and glaucoma. METHODS: This retrospective study involved 1337 eyes of 805 controls between ages 8 and 90, and 250 eyes of 146 patients with glaucoma between the ages of 28 and 95. Subjects were counted as possessing ARAM only if they met the following criteria: (1) a patchy, discrete, glittering appearance on SLO, (2) a distinct, flat, hyper-reflective layer at the internal limiting membrane on at least one B-scan crossing the glittering area and (3) absence of any surface wrinkling retinopathy. The diagnosis of PVD was based on both the patient's clinical examination and imaging data. Frequency tables were used to describe categorical variables and differences were compared by means of χ2 . Analyses were separated based on right and left eye, first on controls and then between glaucomatous eyes and age-similar sex-matched controls. RESULTS: ARAM was found in both healthy controls and patients with glaucoma at similar frequencies. There was no association between having glaucoma and the presence of ARAM. ARAM was not different between the sexes but was associated with age and having a PVD. CONCLUSIONS: This large retrospective study found that ARAM can be seen in healthy controls, is associated with PVD and possibly independently with age, and occurred at similar frequency in glaucomatous eyes.

Cones in ageing and harsh environments: the neural economy hypothesis.

PURPOSE: Cones are at great risk in a wide variety of retinal diseases, especially when there is a harsh microenvironment and retinal pigment epithelium is damaged. We provide established and new methods for assessing cones and retinal pigment epithelium, together with new results. We investigated conditions under which cones can be imaged and could guide light, despite the proximity of less than ideal retinal pigment epithelium. RECENT FINDINGS: We used a variety of imaging methods to detect and localise damage to the retinal pigment epithelium. As age-related macular degeneration is a particularly widespread disease, we imaged clinical hallmarks: drusen and hyperpigmentation. Using near infrared light provided improved imaging of the deeper fundus layers. We compared confocal and multiply scattered light images, using both the variation of detection apertures and polarisation analysis. We used optical coherence tomography to examine distances between structures and thickness of retinal layers, as well as identifying damage to the retinal pigment epithelium. We counted cones using adaptive optics scanning laser ophthalmoscopy. We compared the results of five subjects with geographic atrophy to data from a previous normative ageing study. Using near infrared imaging and layer analysis of optical coherence tomography, the widespread aspect of drusen became evident. Both multiply scattered light imaging and analysis of the volume in the retinal pigment epithelial layer from the optical coherence tomography were effective in localising drusen and hyperpigmentation beneath the photoreceptors. Cone photoreceptors in normal older eyes were shorter than in younger eyes. Cone photoreceptors survived in regions of atrophy, but with greatly reduced and highly variable density. Regular arrays of cones were found in some locations, despite abnormal retinal pigment epithelium. For some subjects, the cone density was significantly greater than normative values in some retinal locations outside the atrophy. SUMMARY: The survival of cones within atrophy is remarkable. The unusually dense packing of cones at some retinal locations outside the atrophy indicates more fluidity in cone distribution than typically thought. Together these findings suggest strategies for therapy that includes preserving cones.

Using Small Samples to Evaluate Normative Reference Ranges for Retinal Imaging Measures.

SIGNIFICANCE: Retinal nerve fiber layer (RNFL) deviation maps often incorrectly score healthy eyes as having wedge defects. This study shows how to identify such problems early in the development of normative databases. PURPOSE: After reference values are embedded in devices, clinicians and researchers often learn about issues that cause false-positive rates in healthy eyes. Here we show a way to detect and address such issues early on. METHODS: The thickness of the RNFL was measured for both eyes of 60 healthy younger adults aged 20 to 31 years and one eye each of 30 healthy older adults aged 54 to 82 years. Deviation maps were developed from the left eyes of the first 30 younger adults, and between-subject variability in the shape of the RNFL was assessed. This was repeated in their right eyes, in the second group of younger adults and in the older adults. RESULTS: For the first group of 30 healthy young adults, between-subject variability in the location of the region of greatest thickness meant that 58% of the pixels below the fifth percentile in the left eyes were from four people whose deviation maps had wedge-shaped patterns, as did the deviation maps for the nine right eyes with 87% of the pixels below the fifth percentile. Wedge patterns were also seen in deviation maps for 8 left eyes and 11 right eyes of the second group of young adults and for 9 eyes of the older adults. CONCLUSIONS: Evaluation of RNFL thickness maps from 30 young adults was sufficient to determine that between-subject variability in the shape of the RNFL can cause wedge patterns in RNFL deviation maps in many healthy eyes.

Comparison of defect depths for sinusoidal and circular perimetric stimuli in patients with glaucoma.

PURPOSE: Clinical use of perimetric testing in patients with glaucoma typically assumes that perimetric defects will be less deep for larger than smaller stimuli. However, studies have shown that very large sinusoidal stimuli can yield similar defects as small circular stimuli. In order to provide guidelines for new perimetric stimuli, we tested patients with glaucoma using five different stimuli and compared defects to their patterns of retinal nerve fibre layer (RNFL) damage. METHODS: Twenty subjects with glaucoma were imaged with optical coherence tomography (OCT) volume scans to allow for en face RNFL images and were also tested on a custom perimetry station with five stimuli: Goldmann sizes III and V, a two-dimensional Gaussian blob (standard deviation 0.5°) and a 0.5 cycle degree-1 sinusoidal grating presented two ways: flickered at 5 Hz, and pulsed for 200 ms instead of flickered. En face RNFL images were reviewed with the visual field locations overlaid, and each location was labelled for a patient as either no visible RNFL defect or as wedge, slit, edge, or diffuse defect. Nineteen age-similar controls were tested with the same stimuli to define depth of defect as difference from mean normal. Bland-Altman analysis was used to test three predictions of neural modelling by making five comparisons. RESULTS: Bland-Altman analysis confirmed the three predictions. The flickered sinusoid gave deeper defects in damaged areas than the pulsed sinusoid (r = 0.25, p < 0.0001). When comparing data for sizes III and V there was increased spread of the data in deeper defects in the direction of size III having deeper defect (r = 0.35, p < 0.0001). The size V stimulus yielded shallower defects than a stimulus of similar size but with blurred edges (r = 0.20, p = 0.0004). CONCLUSIONS: On average, all stimuli produced similar results comparing across type of RNFL damage. However, there were systematic patterns consistent with predictions of neural modelling: in damaged areas, depth of defect tended to be greater for the flickered sinusoid than the pulsed sinusoid, greater for the size III stimulus than the size V stimulus, and greater for the Gaussian blob than for the size V stimulus.

Hybrid Arch Bars Reduce Placement Time and Glove Perforations Compared With Erich Arch Bars During the Application of Intermaxillary Fixation: A Randomized Controlled Trial.

PURPOSE: The purpose of this study was to compare the time for placement and removal, the effect on the gingiva, and the operator safety of the Stryker Universal SMARTLock Hybrid MMF system (Stryker Craniomaxillofacial, Kalamazoo, MI) with traditional Erich arch bars. MATERIALS AND METHODS: We designed a parallel-group, randomized controlled trial to compare the 2 types of arch bars. Patients with mandibular fractures presenting to our institution were enrolled in the study and randomized into 1 of 2 groups: the Erich arch bar group and the hybrid arch bar group. The primary outcome variable was arch bar placement time. Secondary outcomes were glove tears or penetrations during application, gingival appearance score at removal, loose hardware at removal, removal time, and glove tears or penetrations at removal. The groups were compared using t tests. RESULTS: We enrolled 90 patients in the study, with 43 randomized to the Erich arch bar group and 47 randomized to the hybrid arch bar group. The mean application time was 31.3 ± 9.3 minutes for Erich arch bars and 6.9 ± 3.1 minutes for hybrid arch bars (P < .0001). Significantly more glove tears or penetrations occurred during application in the Erich Arch Bar group (0.56 ± 0.91 per application) than in the hybrid group (0.11 ± 0.32 per application) (P = .0025). At removal, no difference in overall gingival appearance or amount of loose hardware was noted. The time for removal was significantly less for the hybrid arch bar group (10.5 ± 5.1 minutes vs 17.9 ± 10.7 minutes, P = .0007). CONCLUSIONS: Hybrid arch bars with bone-borne locking screws offer a number of advantages over traditional Erich arch bars and circumdental wires, including shorter placement and removal times and a greater margin of safety for the operating surgeon as shown by significantly fewer glove tears and penetrations.

What Is the Effect of Treating Mandibular Fractures on Weight and Prealbumin?

PURPOSE: Fracture healing relies on the body to coordinate an inflammatory and anabolic reaction to re-establish osseous union. Although many factors affect this process or even disrupt it, the role of the body's nutritional reserves is not well understood. The purposes of this study were to describe the weight changes and to identify trends in laboratory values commonly used in nutritional assessment during mandibular fracture treatment. MATERIALS AND METHODS: A prospective cohort study was designed. The study cohort included patients who sustained a mandibular fracture from September 1, 2017, to March 31, 2018. The primary outcome variable was the percentage weight change from baseline. Secondary outcome variables included serum albumin and serum prealbumin levels. Weight change was analyzed using a linear mixed model. Paired Wilcoxon tests were used to compare laboratory values with baseline levels. RESULTS: Thirty-nine patients met the inclusion criteria with sufficient follow-up data for analysis. The linear mixed model predicted a peak weight loss of 4.1% of the initial body weight by day 34. The serum prealbumin level increased over the study period (P < .001), and the albumin level was increased from baseline at week 3 (P < .05) but not significantly different from baseline after that time. CONCLUSIONS: During the course of treatment for mandibular fractures, patients lost an average of more than 4% of their body weight. However, the study did not show any meaningful change in nutritional laboratory values. Although it is important for patients and surgeons to be able to anticipate a weight loss of about 4 to 5% during mandibular fracture treatment, it is unlikely that this represents a large challenge to the nutritional status of patients.

Capnography Detection Using Nasal Cannula Is Superior to Modified Nasal Hood in an Open Airway System: A Randomized Controlled Trial.

PURPOSE: The nasal cannula and modified nasal hood are methods used by oral and maxillofacial surgeons to detect expired carbon dioxide during procedural sedation in an open airway system. The purpose of this study was to compare the accuracy of the detection of expired carbon dioxide between the nasal cannula and modified nasal hood. MATERIALS AND METHODS: The authors designed a parallel-group randomized controlled trial to compare the nasal cannula and modified nasal hood. Patients presenting to the authors' institution for outpatient oral and maxillofacial surgery (OMS) using intravenous deep sedation or general anesthesia were randomized to have capnography detection by the modified nasal hood or the nasal cannula. The primary outcome variable was the percentage of accurately captured breaths, as determined by the average number of capnography waveforms per auscultated breath using a precordial stethoscope. The 2 groups were compared using t test. RESULTS: Fifty patients were screened for enrollment in the study. Twenty-five patients were randomized to the nasal cannula group and 25 patients were randomized to the modified nasal hood group. The proportion of accurate waveforms, recorded as a percentage of total breaths, was 95.7 ± 4.7% for the nasal cannula and 75.8 ± 14.1% for the modified nasal hood (P < .0001). CONCLUSIONS: When used for capnography for procedural sedation in an open airway system for routine OMS, the nasal cannula accurately recorded more breaths than the modified nasal hood.

How Much Weight Loss Can Be Expected After Treating Mandibular Fractures?

PURPOSE: Surgeons treating facial trauma are faced with a dilemma: Fracture healing requires a tremendous energy expenditure, yet the treatments for mandibular fractures commonly include dietary limitations. Despite this, almost no studies have attempted to quantify the effect of fracture treatments on patient weight. The purposes of this study were to quantify the effect that mandibular fractures and their treatment have on a patient's weight and to identify risk factors associated with an increased change in weight. MATERIALS AND METHODS: A retrospective cohort study was designed. The patients were considered eligible for inclusion if they sustained a mandibular fracture and had at least 1 follow-up visit within 4 weeks after the fracture from August 1, 2012, to April 30, 2015. The study variables were time since presentation, age, gender, open versus closed treatment, and trauma intensive care unit (TICU) stay. The outcome variable of interest was the percentage weight change from baseline. A linear mixed model was used to analyze the data. RESULTS: A total of 439 patients met the inclusion criteria during the study period. In the final linear mixed model, TICU stay had a significant effect whereas open versus closed treatment did not have a significant effect. The final model predicted a peak weight loss of 4.9% of the initial body weight by day 49. For patients admitted to the TICU, the peak weight loss was 8.8%. CONCLUSIONS: During the course of treatment of mandibular fractures, patients lost an average of almost 5% of their body weight. Closed reduction was not associated with an increased change in weight; however, a stay in the TICU was associated with an increase in weight loss. Further studies will be directed at correlating declining weight with outcomes.

Evidence-Based Clinical Criteria for Computed Tomography Imaging in Odontogenic Infections.

PURPOSE: Odontogenic infections are a common problem in emergency departments and impose a burden on hospital budgets and provider time. Compounding this is the lack of evidence guiding the patient's initial evaluation. The purpose of this study was to derive evidence-based guidelines for the use of computed tomographic (CT) imaging in the management of odontogenic infections. MATERIALS AND METHODS: A prospective cohort study was designed. Patients with an odontogenic infection presenting to the emergency department from November 1, 2016 to November 30, 2017 were eligible for inclusion. The outcome variable was need for CT imaging, which was based on the location of the abscess. The potential predictor variables were demographics, history items, examination findings, and laboratory values. The association between the outcome and predictor variables was determined using classification and regression tree analysis and standard logistic regression analysis. RESULTS: There were 129 patients who met the inclusion criteria and consented to participation. The patients were 53.5% men and the mean age was 42.5 years. The most common fascial spaces involved were vestibular (58.2%), submandibular (18.6%), pterygomandibular (6.2%), buccal (5.4%), and lateral pharyngeal (5.4%). The classification and regression tree analysis identified mandibular inferior border blunting at the body as the best predictor for necessitating a CT scan and identified a mouth opening smaller than 25 mm as the second best predictor. These 2 predictors had an accuracy of 96.9% for needing a CT scan. The logistic regression analysis identified these 2 variables and odynophagia, floor of mouth induration, and white blood cell count as relevant predictors for needing CT imaging. CONCLUSION: The 2 physical examination findings of mandibular inferior border blunting at the body and restricted mouth opening were found to be strongly associated with the need for CT imaging. Further studies should be directed at validating these criteria in larger multicenter studies.

Identifying Glaucomatous Damage to the Macula.

SIGNIFICANCE: Measurements of the macula have been increasingly used to diagnose and manage patients with glaucoma. Asymmetry analysis was clinically introduced to assess damage to the macular ganglion cells in patients with glaucoma, but its effectiveness is limited by high normal between-subject variability. PURPOSE: We aimed to reduce the high normal between-subject variability and improve the potential of asymmetry analysis to identify glaucomatous damage to the macula. METHODS: Twenty patients with glaucoma (aged 57 to 85 years) and 30 age-similar control subjects (aged 53 to 89 years) were recruited from a longitudinal glaucoma study. Participants were imaged with the Spectralis OCT using the posterior pole protocol; measurements of the averaged retinal thickness and ganglion cell layer (GCL) thickness were obtained. We established three zones per hemifield within the central ±9°, based on the lowest between-subject variability that we previously found and the course of retinal nerve fiber layer projections. The criteria for flagging abnormality were at least two contiguous zones when P < 5% or one zone when P < 1% with two-tailed tests. RESULTS: Between-subject variability of the asymmetry analysis for both retinal and GCL thicknesses remained lower than that of the average thickness across each zone in control subjects (F > 2.52, P < .01). Asymmetry analysis of retinal and GCL thicknesses flagged 16 and 18 of 20 patients, respectively. CONCLUSIONS: Between-subject variability was reduced in control subjects using the three zones; our criteria identified glaucomatous damage to the macula in most of the patients. We used high-density B-scans to confirm the patterns of the glaucomatous damage we found in this study.

Novel Technique for Quantifying Retinal Nerve Fiber Bundle Abnormality in the Temporal Raphe.

SIGNIFICANCE: Glaucomatous nasal visual field abnormalities correspond to damage in the temporal raphe-where individual nerve bundles can be visualized. The ability to quantify structural abnormality in the raphe, with a clinically applicable protocol, sets the stage for investigating the raphe as a potential site for assessing early glaucoma. PURPOSE: To develop a clinically applicable imaging and analysis technique for identifying retinal nerve fiber bundle abnormalities in the temporal raphe. METHODS: Spectralis optical coherence tomography scans customized for the temporal raphe were gathered from 30 younger controls, 30 older controls, and 29 patients with glaucoma. An analysis technique was developed based on the reflectance of the nerve fiber bundles. The technique was first developed in the younger controls, and then applied to the older controls to generate normative data for quantifying nerve fiber bundle reflectance abnormalities in the patients with glaucoma. Matrix perimetric data were gathered in the patients with glaucoma to evaluate the reflectance technique's findings. Reflectance abnormality in the patients was defined when the fraction of enface area showing reflectance abnormality was greater than the 95th percentile estimated from controls. Spearman's rho was used to quantify the relation between the total deviation at the perimetric testing locations and the fraction of corresponding enface area showing reflectance abnormality. RESULTS: Twenty-five of the 29 patients had reflectance abnormalities. Eight of these had mild to no perimetric mean deviation abnormality. Similar results were found when perimetric total deviations were compared to reflectance abnormalities in the corresponding enface locations. Spearman's rho comparing the total deviations to reflectance abnormalities found rs(174) = -0.72, P < .001. CONCLUSIONS: The technique typically identified reflectance abnormality when perimetric abnormality was present. It also identified reflectance abnormalities even when perimetric abnormality was mild or absent. The findings support the potential of raphe imaging in detecting early glaucomatous damage.

Retinal putative glial alterations: implication for glaucoma care.

PURPOSE: Gliosis-like retinal alterations, presumed to be activated retinal astrocytes and Müller cells (ARAM), have been reported to occur frequently in patients with glaucoma but rarely in controls. We investigated the association between glaucomatous abnormality and the presence, the extent of retinal region, and the spatial distribution, of hyperreflective retinal alterations on optical coherence tomography (OCT) en-face images, presumed to be ARAM. METHODS: Findings of hyperreflective structures, presumed to be ARAM, in the central retinal ±24 degrees of OCT en-face images (acquired with the SPECTRALIS® OCT) were compared between 35 younger controls, 42 older controls and 38 patients with glaucoma. Presumed ARAM was defined as reflective structures on the en-face images other than retinal vasculature and retinal nerve fibre bundles. Chi-square tests were used to compare the proportion of younger controls vs older controls with presumed ARAM to investigate the effect of ageing, and the proportion of patients vs age-similar older controls with presumed ARAM to investigate the effect of disease. We also investigated the effect of glaucoma on the retinal area with presumed ARAM when it was present; we used an analysis of covariance (ancova) to compare the retinal area with hyperreflectivity in patients vs controls, adjusting for the effects of age and axial length. RESULTS: The mean (S.D.) age of the younger controls, older controls, and patients with glaucoma was 26 (3), 62 (10) and 69 (8) years, respectively. The median (25th quartile, 75th quartile) of the retinal region with the hyperreflective structures, presumed to be ARAM, was zero (0,0), 1 (0,6), and 11 (0,43) degrees square in the younger controls, older controls and patients with glaucoma respectively. The chi-square test investigating the effect of ageing found χ2 (1, N = 77) = 24.8, p < 0.001, and that investigating the effect of disease found χ2 (1, N = 80) = 2.3, p = 0.1. The ancova found F(1, 46) = 10.32, P = 0.02. CONCLUSIONS: There was an effect of ageing on the presence of the hyperreflective structures, presumed to be ARAM, on OCT images. Compared to the presence of hyperreflective structures, the extent of retinal region with the hyperreflective structures has a greater potential of being an indicator of glaucomatous degeneration. Further study is needed to investigate the nature of the relation between glaucomatous abnormality and the extent of the retina with the hyperreflective structures, presumed to be ARAM.

A basis for customising perimetric locations within the macula in glaucoma.

PURPOSE: It has been recognised that the 24-2 grid used for perimetry may poorly sample the macula, which has been recently identified as a critical region for diagnosing and managing patients with glaucoma. We compared data derived from patients and controls to investigate the efficacy of a basis for customising perimetric locations within the macula, guided by en face images of retinal nerve fibre layer (RNFL) bundles. METHODS: We used SD-OCT en face montages (www.heidelbergengineering.com) of the RNFL in 10 patients with glaucoma (ages 56-80 years, median 67.5 years) and 30 age-similar controls (ages 47-77, median 58). These patients were selected because of either the absence of perimetric defect while glaucomatous damage to the RNFL bundles was observed, or because of perimetric defect that did not reflect the extent and locations of the glaucomatous damage that appeared in the RNFL images. We used a customised blob stimulus for perimetric testing (a Gaussian blob with 0.25° standard deviation) at 10-2 grid locations, to assess the correspondence between perimetric defects and damaged RNFL bundles observed on en face images and perimetric defects. Data from the age-similar controls were used to compute total deviation (TD) and pattern deviation (PD) values at each location; a perimetric defect for a location was defined as a TD or PD value of -0.5 log unit or deeper. A McNemar's test was used to compare the proportions of locations with perimetric defects that fell outside the damaged RNFL bundles, with and without accounting for displacement of ganglion cell bodies. RESULTS: All patients but one had perimetric defects that were consistent with the patterns of damaged RNFL bundles observed on the en face images. We found six abnormal perimetric locations of 2040 tested in controls and 132 abnormal perimetric locations of 680 tested in patients. The proportions of abnormal locations that fell outside the damaged RNFL bundles, with and without accounting for displacement of the ganglion cell bodies were 0.08 and 0.07, respectively. The difference between the two proportions did not reach statistical significance (p = 0.5 for a one-tailed test). CONCLUSIONS: We demonstrated that it is effective to customise perimetric locations within the macula, guided by en face images of the RNFL bundles. The perimetric losses found with a 10-2 grid demonstrated similar patterns as the damaged RNFL bundles observed on the en face images.

Evaluating glaucomatous abnormality in peripapillary optical coherence tomography enface visualisation of the retinal nerve fibre layer reflectance.

PURPOSE: Optical coherence tomography (OCT) enface visualisation of the retinal nerve fibre layer (RNFL) reflectance has been found to have some advantages over retinal thickness measures. However, it is not yet clear how abnormalities on enface images relate to findings of abnormalities from other clinical measures such as the circumpapillary retinal nerve fibre layer thickness (cRNFLT). We developed a technique to analyse the RNFL reflectance on the OCT enface images, and to investigate its relation with the cRNFLT. METHODS: Spectralis (www.heidelbergengineering.com) OCT scans of the central retinal ±24° were analysed in the study eye of 31 controls and 33 patients, ages 61 (±9) and 69 (±8) years respectively. Enface slab-images were extracted at 16-24, 24-36, and 24-52 µm from the inner limiting membrane in the temporal raphe, perifoveal and disc regions respectively. Reflectance probability maps were generated for the patients based on the control data. Glaucomatous abnormality was defined on the slab-images when the slab-area with reflectance abnormality was greater than the 95th percentile, and on the cRNFLT when the thickness measure was less than the fifth percentile, of that found in controls. The fraction of slab-image showing reflectance abnormality was compared to cRNFLT in the patient group, using Spearman's rho. Agreement between the findings of abnormality based on cRNFLT and slab-image reflectance was assessed using Cohen's kappa. RESULTS: Slab-image and cRNFLT findings were in agreement for 26/33 eyes; four subjects showed cRNFLT abnormality but not slab-image abnormality, and three subjects showed slab-image abnormality but not cRNFLT abnormality. Spearman's rho found rs (31) = -0.82. The reflectance findings and cRNFLT findings were consistent in 27/33 for both the superior temporal (ST) and inferior temporal (IT) sectors, and Cohen's kappa found 0.53 and 0.61 respectively. CONCLUSION: The surface area of enface slab-images showing RNFL reflectance were strongly related to the cRNFLT measures, and the classification of a subject with glaucoma based on enface reflectance findings and cRNFLT findings had a generally good agreement. The larger retinal area assessed by the enface method preserves the spatial location of the RNFL abnormalities, and makes the technique a useful approach for identifying regions of potential RNFL abnormality for targeted perimetry.