Revisiting the Drasdo Model: Implications for Structure-Function Analysis of the Macular Region

Purpose: To provide a consistent implementation of a retinal ganglion cell (RGC) displacement model proposed by Drasdo et al. for macular structure-function analysis, customizable by axial length (AL). Methods: The effect of axial length on the shape of the inner retina was measured on 235 optical coherence tomography (OCT) scans from healthy eyes, to provide evidence for geometric scaling of structures with eye size. Following this assumption, we applied the Drasdo model to map perimetric stimuli on the radially displaced RGCs using two different methods: Method 1 only displaced the center of the stimuli; Method 2 applied the displacement to every point on the edge of the stimuli. We compared the accuracy of the two methods by calculating, for each stimulus, the number of expected RGC receptive fields and the number RGCs calculated from the histology map, expected to be equivalent. The same calculation was repeated on RGC density maps derived from 28 OCT scans from 28 young healthy subjects (age < 40 years) to confirm our results on clinically available measurements. Results: The size of the retinal structures significantly increased with AL (P < 0.001) and was well predicted by geometric scaling. Method 1 systematically underestimated the RGC counts by as much as 60%. No bias was observed with Method 2. Conclusions: The Drasdo model can effectively account for AL assuming geometric scaling. Method 2 should be used for structure-function analyses. Translational Relevance: We developed a free web App in Shiny R to make our results available for researchers

Visual Field Endpoints Based on Subgroups of Points May Be Useful in Glaucoma Clinical Trials: A Study With the Humphrey Field Analyzer and Compass Perimeter

PRECIS: Visual field endpoints based on average deviation of specific subsets of points rather than all points may offer a more homogenous dataset without necessarily worsening test-retest variability and so may be useful in clinical trials. PURPOSE: To characterize outcome measures encompassing particular subsets of visual field points and compare them as obtained with Humphrey (HVF) and Compass perimeters. METHODS: 30 patients with imaging-based glaucomatous neuropathy performed a pair of 24-2 tests with each of 2 perimeters. Non-weighted mean deviation (MD) was calculated for the whole field and separate vertical hemifields, and again after censoring of points with low sensitivity (MDc) and subsequently including only "abnormal" points with total deviation probability of <5% (MDc5%) or <2% (MDc2%). Test-retest variability was assessed using Bland-Altman 95% limits of agreement (95%LoA). RESULTS: For the whole field, using HVF, MD was -7.5±6.9▒dB, MDc -3.6±2.8▒dB, MDc5% -6.4±1.7▒dB and MDc2% -7.3±1.5▒dB. With Compass MD was -7.5±6.6, MDc -2.9±1.7▒dB, MDc5% -6.3±1.5, and MDC2% -7.9±1.6. The respective 95% LoA were 5.5, 5.3, 4.6 and 5.6 with HVF, and 4.8, 3.7, 7.1 and 7.1 with Compass. The respective number of eligible points were 52, 42±12, 20±11 and 15±9 with HVF, and 52, 41.2±12.6, 10±7 and 7±5 with Compass. With both machines, standard deviation (SD) and 95%LoA increased in hemifields compared to the total field, but this increase was mitigated after censoring. CONCLUSIONS: Restricting analysis to particular subsets of points of interest in the visual field after censoring points with low sensitivity, as compared with using the familiar total field mean deviation, can provide outcome measures with a broader range of mean deviation, a markedly reduced SD and therefore more homogenous dataset, without necessarily worsening test-retest variability

Spatial Summation in the Glaucomatous Macula: A Link With Retinal Ganglion Cell Damage

Purpose: The purpose of this study was to test whether functional loss in the glaucomatous macula is characterized by an enlargement of Ricco's area (RA) through the application of a computational model linking retinal ganglion cell (RGC) damage to perimetric sensitivity. Methods: One eye from each of 29 visually healthy subjects <40 years old, 30 patients with glaucoma, and 20 age-similar controls was tested with a 10-2 grid with stimuli of 5 different area sizes. Structural estimates of point-wise RGC density were obtained from optical coherence tomography (OCT) scans. Structural and functional data from the young healthy cohort were used to estimate the parameters of a computational spatial summation model to generate a template. The template was fitted with a Bayesian hierarchical model to estimate the latent RGC density in patients with glaucoma and age-matched controls. We tested two alternative hypotheses: fitting the data by translating the template horizontally (H1: change in RA) or vertically (H2: loss of sensitivity without a change in RA). Root mean squared error (RMSE) of the model fits to perimetric sensitivity were compared. Ninety-five percent confidence intervals were bootstrapped. The dynamic range of the functional and structural RGC density estimates was denoted by their 1st and 99th percentiles. Results: The RMSE was 2.09 (95% CI = 1.92–2.26) under H1 and 2.49 (95% CI = 2.24–2.72) under H2 (P < 0.001). The average dynamic range for the structural RGC density estimates was only 11% that of the functional estimates. Conclusions: Macular sensitivity loss in glaucoma is better described by a model in which RA changes with RGC loss. Structural measurements have limited dynamic range

Evidence for alterations in fixational eye movements in glaucoma

BACKGROUND: Fixation changes in glaucoma are generally overlooked, as they are not strikingly evident as in macular diseases. Fundus perimetry might give additional insights into this aspect, along with traditional perimetric measures. In this work we propose a novel method to quantify glaucomatous changes in fixation features as detected by fundus perimetry and relate them to the extent of glaucomatous damage. METHODS: We retrospectively analysed fixation data from 320 people (200 normal subjects and 120 with glaucoma) from the Preferred Retinal Locus (PRL) detection of a Compass perimeter. Fixation stability was measured as Bivariate Contour Ellipse Area (BCEA), and using two novel metrics: (1) Mean Euclidean Distance (MED) from the Preferred Retinal Locus, and (2) Sequential Euclidean Distance (SED) of sequential fixation locations. These measures were designed to capture the spread of fixation points, and the frequency of position changes during fixation, respectively. RESULTS: In the age corrected analysis, SED was significantly greater in glaucomatous subjects than controls (P = 0.002), but there was no difference in BCEA (P = 0.15) or MED (P = 0.054). Similarly, SED showed a significant association with Mean Deviation (P  0.14 for both). CONCLUSION: Changes in the scanning pattern detected by SED are better than traditional measures of fixation spread (BCEA) for describing the changes in fixation stability observed in glaucoma

Urinary and sexual outcomes in long-term (5+ years) prostate cancer disease free survivors after radical prostatectomy

<p>Abstract</p> <p>Background</p> <p>After long term disease free follow up (FUp) patients reconsider quality of life (QOL) outcomes. Aim of this study is assess QoL in prostate cancer patients who are disease-free at least 5 years after radical prostatectomy (RP).</p> <p>Methods</p> <p>367 patients treated with RP for clinically localized pCa, without biochemical failure (PSA ≤ 0.2 ng/mL) at the follow up ≥ 5 years were recruited.</p> <p>Urinary (UF) and Sexual Function (SF), Urinary (UB) and Sexual Bother (SB) were assessed by using UCLA-PCI questionnaire. UF, UB, SF and SB were analyzed according to: treatment timing <it>(age at time of RP, FUp duration, age at time of FUp)</it>, tumor characteristics <it>(preoperative PSA, TNM stage, pathological Gleason score)</it>, nerve sparing (NS) procedure, and hormonal treatment (HT).</p> <p>We calculated the differences between 93 NS-RP without HT (group A) and 274 non-NS-RP or NS-RP with HT (group B). We evaluated the correlation between function and bother in group A according to follow-up duration.</p> <p>Results</p> <p>Time since prostatectomy had a negative effect on SF and a positive effect SB (both p < 0.001). Elderly men at follow up experienced worse UF and SF (p = 0.02 and p < 0.001) and better SB (p < 0.001).</p> <p>Higher stage PCa negatively affected UB, SF, and SB (all: p ≤ 0.05). NS was associated with better UB, SF and SB (all: p ≤ 0.05); conversely, HT was associated with worse UF, SF and SB (all: p ≤ 0.05).</p> <p>More than 8 years after prostatectomy SF of group A and B were similar. Group A subjects (NS-RP without HT) demonstrated worsening SF, but improved SB, suggesting dissociation of the correlation between SF and SB over time.</p> <p>Conclusion</p> <p>Older age at follow up and higher pathological stage were associated with worse QoL outcomes after RP. The direct correlation between UF and age at follow up, with no correlation between UF and age at time of RP suggests that other issues (i.e: vascular or neurogenic disorders), subsequent to RP, are determinant on urinary incontinence. After NS-RP without HT the correlation between SF and SB is maintained for 7 years, after which function and bother appear to have divergent trajectories.</p