Autofluorescence Lifetimes in Patients With Choroideremia Identify Photoreceptors in Areas With Retinal Pigment Epithelium Atrophy.

The purpose of this study was to investigate fundus autofluorescence lifetimes in patients with choroideremia and to identify tissue-specific lifetime characteristics and potential prognostic markers. Autofluorescence lifetimes of the retina were measured in two spectral channels (498-560 nm and 560-720 nm) in patients with choroideremia and age-matched healthy controls. Furthermore, autofluorescence intensities and spectral-domain optical coherence tomography (OCT) data were acquired and compared to fundus autofluorescence lifetime data. Sixteen eyes from 8 patients with advanced choroideremia (mean ± SD age, 55 ± 13 years) were included in this study and compared with 10 age-matched healthy participants. Whereas fundus autofluorescence intensity measurement identified areas of remaining retinal pigment epithelium (RPE), autofluorescence lifetime maps identified areas with remaining photoreceptor layers in OCT but RPE atrophy. In these areas, mean (±SEM) lifetimes were 567 ± 59 ps in the short and 603 ± 49 ps in the long spectral channels (+98% and +88% compared to controls). In areas of combined RPE atrophy and loss of photoreceptors, autofluorescence lifetimes were significantly prolonged by 1116 ± 63 ps (+364%) in the short and by 915 ± 52 ps (+270%) in the long spectral channels compared with controls. Because autofluorescence lifetimes identify areas of remaining photoreceptors in the absence of RPE, this imaging modality may be useful to monitor disease progression in the natural course of disease and in context of potential future therapeutic interventions

Intravitreal Injections with Vascular Endothelial Growth Factor Inhibitors: A Practical Approach

Intravitreal injections with vascular endothelial growth factor inhibitors constitute the most prevalent ophthalmic procedure in developed countries. Historically, there has been steady growth in the number of treatments performed of this kind, and projection studies estimate further growth in such treatments in the future. We provide a practical approach to intravitreal injections and discuss important aspects relating to the setting, the patient, the procedure, and the information given to the patient

Divergence bias in Hess compared to Harms screen strabismus testing

The Hess and the Harms screen test each have different testing distances. While the Harms screen test is usually performed at 2.5 m, the Hess screen test is performed at 0.5 m. The geometry of the closer testing distance of the Hess screen test requires an increase of the convergence angle by 6°. This study investigates the quantitative differences between the two frequently employed screen tests. Ocular deviation of 18 normal subjects and 36 patients with congenital or acquired paralytic or concomitant strabismus were assessed with a complete orthoptic examination including alternate prism cover testing at near (nPCT) and far (fPCT), as well as Hess and Harms screen testing. One-way ANOVA was used for statistical analysis. The Hess test recorded more overall exodeviation compared to the Harms test for patients (mean difference -3.50°, 95% limits of agreement (CI) = [-4.79, -2.21], p < .001), and controls (mean difference -1.78°, CI = [-2.99, -0.56], p = .004). For vertical deviations, there was no statistically significant difference between the two tests for patients (mean difference +0.75°, CI = [-0.41, +1.91], p = .251), and controls (mean difference -0.28°, CI = [-0.68, -0.11], p = 0.231). This study emphasizes the importance to consider the divergence bias when comparing the Hess to the Harms screen test, which is likely explained by the greater vergence demand dependent on the closer testing distance. The exodeviation shift tended to be more pronounced in patients than controls, which may imply that patients with strabismus have an impaired convergence drive. Keywords: Harms test; Hess test; prism cover test; strabismus; tangent screen test; vergence

Characterization of the retinal changes of the 3×Tg-AD mouse model of Alzheimer’s disease

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder whose diagnosis remains a notable challenge. The literature suggests that cerebral changes precede AD symptoms by over two decades, implying a significantly advanced stage of AD by the time it is usually diagnosed. In the study herein, texture analysis was applied to computed optical coherence tomography ocular fundus images to identify differences between a group of the transgenic mouse model of the Alzheimer’s disease (3×Tg-AD) and a group of wild-type mice, at the ages of one and two-months-old. A substantial difference between groups was found at both time-points across all neuroretina’s layers. Here, the inner nuclear layer stands out both in the level of statistically significant differences and on the extension of these differences which span through the imaged area. Also, the progression of AD is suggested to be spotted by texture analysis as demonstrated by the significant difference found in the inner plexiform and the outer nuclear layers from the age of one to the age of two-months-old. These findings demonstrate the potential of the use of the retina and texture analysis to the diagnosis of AD and monitor AD progression. Besides, the differences between groups found in this study suggest that the 3×Tg-AD model may be inappropriate to study early changes associated with the AD and other animal models should be tested following the same path and rationale. Moreover, these results also suggest that the human genes present in these transgenic mice may have an impact on the neurodevelopment of offspring which would justify the significant changes found at the age of one-month-old.This study was funded by The Portuguese Foundation for Science and Technology (FCT) throught PTDC/EMD-EMD/28039/2017, PEst-UID/NEU/04539/2019, UID/Multi/04621/2013 and UID/04950/2017, and by FEDER-COMPETE through POCI-01-0145-FEDER-028039 and POCI-01-0145-FEDER-007440.info:eu-repo/semantics/publishedVersio

Artificial intelligence for morphology-based function prediction in neovascular age-related macular degeneration

Spatially-resolved mapping of rod- and cone-function may facilitate monitoring of macular diseases and serve as a functional outcome parameter. However, mesopic and dark-adapted two-color fundus-controlled perimetry (FCP, also called "microperimetry") constitute laborious examinations. We have devised a machine-learning-based approach to predict mesopic and dark-adapted (DA) retinal sensitivity in eyes with neovascular age-related macular degeneration (nAMD). Extensive psychophysical testing and volumetric multimodal retinal imaging data were acquired including mesopic, DA red and DA cyan FCP, spectral-domain optical coherence tomography and confocal scanning laser ophthalmoscopy infrared reflectance and fundus autofluorescence imaging. With patient-wise leave-one-out cross-validation, we have been able to achieve prediction accuracies of (mean absolute error, MAE [95% CI]) 3.94 dB [3.38, 4.5] for mesopic, 4.93 dB [4.59, 5.27] for DA cyan and 4.02 dB [3.63, 4.42] for DA red testing. Partial addition of patient-specific sensitivity data decreased the cross-validated MAE to 2.8 dB [2.51, 3.09], 3.71 dB [3.46, 3.96], and 2.85 dB [2.62, 3.08]. The most important predictive feature was outer nuclear layer thickness. This artificial intelligence-based analysis strategy, termed "inferred sensitivity", herein, enables to estimate differential effects of retinal structural abnormalities on cone- and rod-function in nAMD, and may be used as quasi-functional surrogate endpoint in future clinical trials

Light sensitivity within areas of geographic atrophy secondary to age-related macular degeneration

Purpose: To investigate residual sensitivity within geographic atrophy (GA) secondary to age-related macular degeneration. Methods: Mesopic and dark-adapted (DA) cyan and red light sensitivity (Goldmann III) were investigated using fundus-controlled perimetry (microperimetry). Test points were placed within GA along an “iso-hull” with a distance of −0.645° to the atrophy boundary. The false-positive response rate was determined with suprathreshold stimuli to the optic disc (Heijl-Krakau method) and used to compute the expected sensitivity measurements for the assumption of absolute scotomata. The outermost visible retinal layer on spectral-domain optical coherence tomography at the location of each test point was determined. Results: Thirty eyes of 36 patients (75.55 ± 7.93 years; 19 female) from the prospective natural history study Directional Spread in Geographic Atrophy (NCT02051998), with a total of 1380 threshold determinations were analyzed. The measured sensitivities were significantly (P Conclusions: Measured sensitivities within the inner junctional zone of GA may not be purely explained by patient-specific false-positive response rates or other reliability indices. The marked influence of the outer retinal configuration on measured sensitivity may be indicative of residual cone function within GA at the inner junctional zone.</p