Discriminating early-stage diabetic retinopathy with subjective and objective perimetry

Introduction: To prevent progression of early-stage diabetic retinopathy, we need functional tests that can distinguish multiple levels of neural damage before classical vasculopathy. To that end, we compared multifocal pupillographic objective perimetry (mfPOP), and two types of subjective automated perimetry (SAP), in persons with type 2 diabetes (PwT2D) with either no retinopathy (noDR) or mild to-moderate non-proliferative retinopathy (mmDR). Methods: Both eyes were assessed by two mfPOP test methods that present stimuli within either the central ±15° (OFA15) or ±30° (OFA30), each producing per-region sensitivities and response delays. The SAP tests were 24-2 Short Wavelength Automated Perimetry and 24-2 Matrix perimetry. Results: Five of eight mfPOP global indices were significantly different between noDR and mmDR eyes, but none of the equivalent measures differed for SAP. Per-region mfPOP identified significant hypersensitivity and longer delays in the peripheral visual field, verifying earlier findings. Diagnostic power for discrimination of noDR vs. mmDR, and normal controls vs. PwT2D, was much higher for mfPOP than SAP. The mfPOP per-region delays provided the best discrimination. The presence of localized rather than global changes in delay ruled out iris neuropathy as a major factor. Discussion: mfPOP response delays may provide new surrogate endpoints for studies of interventions for early-stage diabetic eye damage.</p

Early diabetic eye damage:Comparing detection methods using diagnostic power

It is now clear that retinal neuropathy precedes classical microvascular retinopathy in diabetes. Therefore, tests that underpin useful new endpoints must provide high diagnostic power well before the onset of moderate diabetic retinopathy. Hence, we compare detection methods of early diabetic eye damage. We reviewed data from a range of functional and structural studies of early diabetic eye disease and computed standardized effect size as a measure of diagnostic power, allowing the studies to be compared quantitatively. We then derived minimum performance criteria for tests to provide useful clinical endpoints. This included the criteria that tests should be rapid and easy so that children with type 1 diabetes can be followed into adulthood with the same tests. We also defined attributes that lend test data to further improve performance using Machine/Deep Learning. Data from a new form of objective perimetry suggested that the criteria are achievable.</p

An objective perimetry study of central versus peripheral sensitivities and delays in age-related macular degeneration

PURPOSE: The purpose of this study was to compare central versus peripheral retinal sensitivities and delays in neovascular age-related macular degeneration (nAMD) using US Food and Drug Administration (FDA)-cleared multifocal pupillographic objective perimetry (mfPOP). METHODS: We recruited 18 patients with nAMD and commenced Pro re nata intravitreal anti- vascular endothelial growth factor (VEGF) injection. We compared macular (±15 degrees) and wide-field (±30 degrees) mfPOP variants. We examined temporal correlations between treated and untreated fellow eyes. We fitted linear models to selected treatment patterns, and compared the ability of central versus peripheral responses to predict the need for treatment. RESULTS: Central sensitivity decreased by −2.23 ± 0.051 dB/month (P < 0.0002) in treated eyes, and −0.17 ± 0.07 dB/month (P = 0.033) in untreated eyes. Treated eyes showed quicker central responses by 13.08 ± 3.77 ms than untreated eyes (P = 0.001). Based on peripheral responses, we identified two eye-types. Among positive-eyes peripheral sensitivity increased by 9.88 ± 4.41 dB (P = 0.042) before treatment; delays increased by 3.49 ± 1.75 ms/month (P = 0.049). For negative-eyes peripheral delays were shorter a month before treatment by 9.38 ± 3.59 ms (P = 0.013). Correlations between treatment and peripheral sensitivities or delays peaked at 1 to 2 months post-treatment. Peripheral data significantly determined treatment frequency and final acuity (all P < 0.044). CONCLUSIONS: Peripheral macular function of treated and untreated eyes divided eyes into positive and negative groups. Those peripheral responses determined outcomes; changes preceding active disease by 1 to 3 months. Overall, mfPOP may provide potential biomarkers to assist nAMD management. TRANSLATIONAL RELEVANCE: Objective perimetry may identify the requirement for treatment in nAMD that accords with the decision of a skilled clinician based on optical coherence tomography (OCT) and clinical findings

Complex cell receptive fields: evidence for a hierarchical mechanism

Simple cells in the primary visual cortex have segregated ON and OFF subregions in their receptive fields, while complex cells have overlapping ON and OFF subregions. These two cell types form the extremes at each end of a continuum of receptive field types. Hubel and Wiesel in 1962 suggested a hierarchical scheme of processing whereby spatially offset simple cells drive complex cells. Simple and complex cells are often classified by their responses to moving sine wave gratings: simple cells have oscillatory responses while complex cells produce unmodulated responses. Here, using moving gratings as stimuli, we show that a significant number of cells that display low levels of response modulation at high contrasts demonstrate high levels of response modulation at low contrasts. Most often a drifting low contrast grating generates a large phasic response at the fundamental frequency of the grating (F1) and a smaller but significant phasic response that is approximately 180 deg out-of-phase with the F1 component. We present several models capable of capturing the effects of stimulus contrast on complex cell responses. The model that best reproduces our experimental results is a variation of the classical hierarchical model. In our model several spatially offset simple cells provide input to a complex cell, with each simple cell exhibiting a different contrast response function. At low contrasts only one of these simple cells is sufficiently excited to reveal its receptive field properties. As contrast is increased additional spatially offset simple cells with higher contrast thresholds add their responses to the overall spiking activity