Cancer control collaborations between China and African countries.

Over the past decade, China has emerged as Africa's largest trade partner and source of foreign direct investment, with public health ranked as a top priority in China-Africa collaborations. During the same period, cancer has emerged as a leading cause of death in Africa, with more than 700 000 deaths per year and projections of more than 1 million deaths per year by 2030. In this Review, we explore the effects of increasing China-Africa collaborations on cancer control in Africa. We review the published literature on health-care assistance, research, education and training, and infrastructure and present the results of an institutional review board-approved survey of African oncology health-care professionals and institutional leaders that assessed their perception of the effects of China-Africa collaborations. From peer-reviewed articles and grey literature, we found that the number of China-Africa collaborations have grown substantially over the past decade in different areas, especially in patient care and infrastructure. Research publications have also surged in quantity in the past decade compared with previous years. However, the survey results suggest research collaborations remain infrequent and that medical professionals in African cancer centres rarely participate in direct research collaborations with Chinese institutions. The Review also highlights the challenges and benefits of increasing China-Africa collaborations. Challenges include insufficient monitoring and evaluation of the projects in Africa and poor coordination and alignment of the various initiatives. The benefits of these collaborations for Africa include improved health outcomes, strengthened health systems, and socioeconomic development. Benefits are also apparent for China, such as securing energy and resource supplies, expanded trade and investment opportunities, and improved diplomatic relations. Overall, China-Africa collaborations are increasing and having a substantial effect in both China and the African continent. Recommendations to minimise the challenges and maximise the benefits for more positive consequences on cancer control in Africa are discussed.

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.

Cancer in sub-Saharan Africa: a Lancet Oncology Commission.

In sub-Saharan Africa (SSA), urgent action is needed to curb a growing crisis in cancer incidence and mortality. Without rapid interventions, data estimates show a major increase in cancer mortality from 520 348 in 2020 to about 1 million deaths per year by 2030. Here, we detail the state of cancer in SSA, recommend key actions on the basis of analysis, and highlight case studies and successful models that can be emulated, adapted, or improved across the region to reduce the growing cancer crises. Recommended actions begin with the need to develop or update national cancer control plans in each country. Plans must include childhood cancer plans, managing comorbidities such as HIV and malnutrition, a reliable and predictable supply of medication, and the provision of psychosocial, supportive, and palliative care. Plans should also engage traditional, complementary, and alternative medical practices employed by more than 80% of SSA populations and pathways to reduce missed diagnoses and late referrals. More substantial investment is needed in developing cancer registries and cancer diagnostics for core cancer tests. We show that investments in, and increased adoption of, some approaches used during the COVID-19 pandemic, such as hypofractionated radiotherapy and telehealth, can substantially increase access to cancer care in Africa, accelerate cancer prevention and control efforts, increase survival, and save billions of US dollars over the next decade. The involvement of African First Ladies in cancer prevention efforts represents one practical approach that should be amplified across SSA. Moreover, investments in workforce training are crucial to prevent millions of avoidable deaths by 2030. We present a framework that can be used to strategically plan cancer research enhancement in SSA, with investments in research that can produce a return on investment and help drive policy and effective collaborations. Expansion of universal health coverage to incorporate cancer into essential benefits packages is also vital. Implementation of the recommended actions in this Commission will be crucial for reducing the growing cancer crises in SSA and achieving political commitments to the UN Sustainable Development Goals to reduce premature mortality from non-communicable diseases by a third by 2030.

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.

Detection and discrimination of achromatic contrast: A ganglion cell perspective.

The magnocellular (MC) pathway in the primate has much higher achromatic contrast sensitivity than the parvocellular (PC) pathway, and is implicated in luminance contrast detection. But MC pathway responses tend to saturate at lower achromatic contrast than do PC pathway responses. It has been proposed that the PC pathway plays a major role in discriminating suprathreshold achromatic contrast, because the MC pathway is in saturation. This has been termed the pulsed-pedestal protocol. To test this hypothesis, responses of MC and PC pathway ganglion cells have been examined under suprathreshold conditions with stimulus configurations similar to those in psychophysical tests. For MC cells, response saturation was much less for flashed or moving edges than for sinusoidal modulation, and MC cell thresholds predicted for these stimuli were similar to psychophysical discrimination (and detection) data. Results suggest the protocol is not effective in segregating MC and PC function.

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.

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.

Practical application of laparoscopic oviductal artificial insemination for the propagation of domestic cats and wild felids.

AI was first reported in cats almost 50 years ago but, unlike AI in other domesticated animals (e.g. dogs, cattle, horses), has not been widely used for routine propagation by veterinarians or breeders. Anatomical and physiological challenges with cats have hindered the efficiency of AI using standardised transcervical approaches applied to other species. Development of laparoscopic oviductal AI (LO-AI) has helped overcome some of these barriers and, during the past 7 years, produced high pregnancy percentages (>70%) in domestic cats using both fresh collected and frozen-thawed semen and resulted in the birth of full-term offspring in three cat hereditary disease models and six wild cat species (ocelot, Pallas's cat, fishing cat, sand cat, tiger, clouded leopard). The standard approach involves exogenous gonadotrophin treatment (typically equine chorionic gonadotrophin followed by porcine LH) to induce ovarian follicular growth and ovulation, with laparoscopic visualisation of the oviductal ostium for direct intraluminal insemination with low numbers of spermatozoa. Similar ovarian synchronisation and insemination approaches have been used with wild felids, but frequently must be refined on a species-by-species basis. From a practical perspective, LO-AI in domestic cats now has adequate efficiency for applied use as a reproductive service in veterinary practices that possess basic laparoscopy expertise.

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.

Characterization of the behavior and reproductive endocrinology of giant river otters (Pteronura brasiliensis) in managed care.

Propagation of giant river otters (GRO) in zoos is inconsistent: some pairs never reproduce while others are prolific in producing young but can be hindered by low cub survival. Developing effective breeding programs requires understanding normal reproductive parameters and behavior. Fecal samples were collected for 6-16 months from five breeding pairs, two individual females, and one female pair at seven zoos, and analyzed for fecal progesterone, estrogen, testosterone, and glucocorticoid (FGM) metabolites via enzyme immunoassay. Enclosure characteristics and management routines were recorded at six facilities where behavior was assessed over 1 week. Median fecal progestogens during pregnancy and pseudopregnancy were ∼2.5-3.8× greater than basal concentrations. Gestation lasted 66.5 ± 3.5 days (62-70 days); pseudopregnancies lasted 58 ± 11.6 days (41-69 days). Elevated progestogens indicate ovulation but cannot distinguish pregnancy from pseudopregnancy. Periodically sustained, elevated progestogens observed in two females housed without a male indicated spontaneous ovulation. Elevations in fecal estrogens were not associated with estrus, and seasonality in male testosterone was not observed. Wavering scream and contact call vocalizations among reproductively successful males and females, respectively, suggested the importance of social communication. Most facilities housing successful pairs had larger enclosures with more water than land area, vegetation, and limited public exposure. Baseline FGM were negatively correlated with enclosure size and percentage of water area (p < 0.05), and lower baseline FGM were associated with reproductive success (p < 0.05). These results suggest that housing GRO in spacious enclosures with open water and some insulation from disturbance might promote appropriate behavior, lower FGM, and reproduction.

Using perimetric data to estimate ganglion cell loss for detecting progression of glaucoma: a comparison of models.

PURPOSE: Models relating perimetric sensitivities to ganglion cell numbers have been proposed for combining structural and functional measures from patients with glaucoma. Here we compared seven models for ability to differentiate progressing and stable patients, testing the hypothesis that the model incorporating local spatial scale would have the best performance. METHODS: The models were compared for the United Kingdom Glaucoma Treatment Study (UKGTS) data for the right eyes of 489 patients recently diagnosed with glaucoma. The SITA 24-2 program was utilised for perimetry and Stratus OCT fast scanning protocol for thickness of circumpapillary retinal nerve fibre layer (RNFL). The first analysis defined progression in terms of decline in RNFL thickness. The highest and lowest quintiles (22 subjects per group) were identified for change in thickness of inferior temporal (IT), superior temporal (ST), and global RNFL (µm year-1 ); a two-way anova was used to look for differences between the models in ability to discriminate the two quintiles. The second analysis defined a 'progression group' as those who were flagged by the UKGTS criteria as having progressive loss in perimetric sensitivity, and a 'no progression' group as those with rate of change in Mean Deviation (MD) closest to 0 dB year-1 (87 subjects per group). The third analysis characterised variability of retinal ganglion cell (RGC) models for the two groups in the second analysis, using the standard deviation of residuals from linear regression of ganglion cell number over time to compute Coefficient of Variation (CoV). RESULTS: The first analysis produced a negative result because the three anovas found no effect of model or interaction of model and group (F6,294 < 3.1, p > 0.08). There was an effect of group only for the anova with the ST sector (F6,294 = 12.2, p < 0.001). The second analysis also produced a negative result, because ROC areas were in the range 0.69-0.72 for all models. The third analysis found that even when variability in MD was low, the CoV was so large that test-retest variation could include 100% loss of ganglion cells. CONCLUSIONS: Two very different approaches for testing the hypothesis both gave a negative result. For all seven ganglion cell models, rates of ganglion cell loss were highly affected by fluctuations in height of the hill of vision. Methods for reducing effects of between-visit variability are needed in order to assess progression by relating perimetric sensitivities and ganglion cell numbers.

Assessing assumptions of a combined structure-function index.

PURPOSE: Medeiros et al. developed a combined structure-function index for glaucoma by combining two ganglion cell models developed by Harwerth et al. The current study assessed assumptions of the Medeiros combined structure-function index by evaluating whether the two Harwerth models gave similar distributions of ganglion cells in an independent dataset. METHODS: The Harwerth models were applied to our previously published data for retinal nerve fibre layer (RNFL) thickness (Stratus OCT 3.4) and visual field sensitivities (24-2 SITA Standard) from one eye each of 51 patients with glaucoma and 62 age-similar control subjects free of eye disease. RNFL thicknesses and perimetric sensitivities were converted to ganglion cell numbers using the Harwerth model for perimetry and the Harwerth model for RNFL. These two estimates of ganglion cell number were compared for the inferior temporal (IT) and superior temporal (ST) sectors of the optic disc and the corresponding visual field locations. Comparisons were made with 14 visual field locations per sector (including a point in the macula for the inferior temporal sector) and with 13 locations (no point in the macula). Data for controls and patients were analysed separately, comparing mean values for RNFL perimetry models. Bonferroni correction was applied to control for repeated tests of significance. The difference between mean values for the RNFL and perimetry models was quantified by equating the means for controls through reduction of the assumed axon diameter used by the RNFL model. RESULTS: For the control group, the Harwerth RNFL model yielded smaller mean number of retinal ganglion cells than the Harwerth perimetry model, 23-47% lower (t > 13, p < 0.0001). This corresponded to mean axon diameters from 0.48 to 0.69 µm, with the smallest axons when the 14th location in the macula was included. With these new axon diameters, estimates of ganglion cell numbers for patients were still lower than for the RNFL model, by 19-28% (t > 6.5, p < 0.0001). CONCLUSIONS: The Harwerth RNFL model consistently gave lower ganglion cell numbers than the Harwerth perimetry model, and this discordance persisted in patients even after reducing assumed axon diameter for controls. This finding contradicts the assumptions of the Medeiros structure-function index.