Background: To evaluate a fully automated vascular density (VD), skeletal density (SD) and fractal dimension (FD) method for the longitudinal analysis of retinal vein occlusion (RVO) eyes using projection-resolved optical coherence tomography angiography (OCTA) images and to evaluate the association between these quantitative variables and the visual prognosis in RVO eyes.
Methods: Retrospective longitudinal observational case series. Patients presenting with RVO to Creteil University Eye Clinic between October 2014 and December 2018 and healthy controls were retrospectively evaluated. Group 1 consisted of central RVO (CRVO) eyes, group 2 consisted of eyes with branch RVO (BRVO) and group 3 of healthy control eyes. OCTA acquisitions (AngioVue RTVue XR Avanti, Optovue, Inc., Freemont, CA) were performed at baseline and last follow up visit. VD, SD, and FD analysis were computed on OCTA superficial and deep vascular complex (SVC, DVC) images at baseline and final follow up using an automated algorithm. Logistic regression was performed to find if and which variable (VD, SD, FD) was predictive for the visual outcome.
Results: Forty-one eyes, of which 21 consecutive eyes of 20 RVO patients (13 CRVO in group 1, 8 BRVO in group 2), and 20 eyes of 20 healthy controls were included. At the level of SVC, VD and FD were significantly lower in RVO eyes compared to controls (P<0.0001 and P=0.0008 respectively). Best-corrected visual acuity (BCVA) at last follow-up visit was associated with baseline VD (P=0.013), FD (P=0.016), and SD (P=0.01) at the level of the SVC, as well as with baseline FD at the DVC level (P=0.046).
Conclusions: Baseline VD, SD, and FD are associated with the visual outcome in RVO eyes. These parameters seem valuable biomarkers and may help improve the evaluation and management of RVO patients.
Abstract: The rare disease of chronic infantile neurological cutaneous and articular (CINCA) syndrome, is caused by the over-secretion of interleukin (IL)-1β due to a gain-of-function NLRP3 gene mutation in the autosomal chromosome which often involves in eyes. In this report, we studied a 9-year-old girl with CINCA. The eyes were also involved and presented bilateral papilledema. Genetic testing revealed that the symptoms were caused by a novel gene mutation site (c.913G>A, p. D305N) in conservative domain exon-3 of NLRP3 which is gain-function gene of CINCA. The patient had the characteristic facial features, frontal fossa and saddle nose, manifested the generalized urticaria-like skin rash at two weeks after birth, periodic fever 6 months after birth, sensorineural deafness at 7 years old, and bilateral papilledema, aseptic meningitis and knee arthropathy at 9 years old. White cell counts, C-reactive protein increased and intracranial pressure raised to 300 mmH2O. The meningeal thickening enhanced by gadolinium in magnetic resonance imaging (MRI). Based on clinical features and genetic test, the girl was diagnosed bilateral papilledema secondary to CINCA and administered prednisone and lowered intracranial pressure medicine to resolve symptoms. With 3-year follow-up, patient had no inflammatory flare-up with visual acuity improvement. The finding of novel genetic mutation site (p. D305N) in NLRP3 gene expanded genotype spectrum associated with CINCA. This case also expanded the cause spectrum of papilledema and it highlighted systemic disease history for patients with bilateral papilledema.
Abstract: Anthropometry can analyze the size, weight, and proportion of the human body objectively and quantitatively to supplement the visual assessment. Various non-invasive three-dimensional (3D) anthropometric techniques have been applied to assess soft tissues’ 3D morphology in the clinical practice. Among them, non-invasive stereophotogrammetry and laser scanning techniques are becoming increasingly popular in craniofacial surgery and plastic surgery. They have been applied for craniofacial growth estimation and morphometric investigation, genetic and acquired malformation diagnosis, as well as orthodontic or surgical treatment arrangement and outcome evaluation. However, few studies have been published for assessing the 3D morphology of soft tissues in the periorbital region. This paper reviews the studies involving the application and evaluation of the increasingly popular 3D photogrammetry in the periorbital region. These studies proposed detailed and standardized protocols for three-dimensionally assessing linear, curvilinear, angular, as well as volumetric measurements, and verified its high reliability in the periorbital region (even higher than caliper-derived direct measurements). In the future, reliable and accurate 3D imaging techniques, as well as standardized analyzing protocols, may find applications in following up morphological growth, preoperatively diagnosing and assessing patient periorbital conditions, planning surgical procedures, postoperatively evaluating treatment outcomes of a specific procedure, and comparing the differences in surgical results between various procedures, studies, as well as populations.
Abstract: Navigation technology in ophthalmology, colloquially called “eye-tracking”, has been applied to various areas of eye care. This approach encompasses motion-based navigation technology in both ophthalmic imaging and treatment. For instance, modern imaging instruments use a real-time eye-tracking system, which helps to reduce motion artefacts and increase signal-to-noise ratio in imaging acquisition such as optical coherence tomography (OCT), microperimetry, and fluorescence and color imaging. Navigation in ophthalmic surgery has been firstly applied in laser vision corrective surgery and spread to involve navigated retinal photocoagulation, and positioning guidance of intraocular lenses (IOL) during cataract surgery. It has emerged as one of the most reliable representatives of technology as it continues to transform surgical interventions into safer, more standardized, and more predictable procedures with better outcomes. Eye-tracking is essential in refractive surgery with excimer laser ablation. Using this technology for cataract surgery in patients with high preoperative astigmatism has produced better therapeutic outcomes. Navigated retinal laser has proven to be safer and more accurate compared to the use of conventional slit lamp lasers. Eye-tracking has also been used in imaging diagnostics, where it is essential for proper alignment of captured zones of interest and accurate follow-up imaging. This technology is not routinely discussed in the ophthalmic literature even though it has been truly impactful in our clinical practice and represents a small revolution in ophthalmology.
Background: Soft drusen and basal linear deposit (BLinD) are two forms of the same extracellular lipid rich material that together make up an Oil Spill on Bruch’s membrane (BrM). Drusen are focal and can be recognized clinically. In contrast BLinD is thin and diffusely distributed, and invisible clinically, even on highest resolution OCT, but has been detected on en face hyperspectral autofluorescence (AF) imaging ex vivo. We sought to optimize histologic hyperspectral AF imaging and image analysis for recognition of drusen and sub-RPE deposits (including BLinD and basal laminar deposit), for potential clinical application.
Methods: Twenty locations specifically with drusen and 12 additional locations specifically from fovea, perifovea and mid-periphery from RPE/BrM flatmounts from 4 AMD donors underwent hyperspectral AF imaging with 4 excitation wavelengths (λex 436, 450, 480 and 505 nm), and the resulting image cubes were simultaneously decomposed with our published non-negative matrix factorization (NMF). Rank 4 recovery of 4 emission spectra was chosen for each excitation wavelength.
Results: A composite emission spectrum, sensitive and specific for drusen and presumed sub-RPE deposits (the SDr spectrum) was recovered with peak at 510–520 nm in all tissues with drusen, with greatest amplitudes at excitations λex 436, 450 and 480 nm. The RPE spectra of combined sources Lipofuscin (LF)/Melanolipofuscin (MLF) were of comparable amplitude and consistently recapitulated the spectra S1, S2 and S3 previously reported from all tissues: tissues with drusen, foveal and extra-foveal locations.
Conclusions: A clinical hyperspectral AF camera, with properly chosen excitation wavelengths in the blue range and a hyperspectral AF detector, should be capable of detecting and quantifying drusen and sub-RPE deposits, the earliest known lesions of AMD, before any other currently available imaging modality.
Background: Cells of the retinal pigment epithelium (RPE) accumulate different kinds of granules (lipofuscin, melanolipofuscin, melanosomes) within their cell bodies, with lipofuscin and melanolipofuscin being autofluorescent after blue light excitation. High amounts of lipofuscin granules within the RPE have been associated with the development of RPE cell death and age-related macular degeneration (AMD); however, this has not been confirmed in histology so far. Here, based on our previous dataset of RPE granule characteristics, we report the characteristics of RPE cells from human donor eyes that show either high or low numbers of intracellular granules or high or low autofluorescence (AF) intensities.
Methods: RPE flatmounts of fifteen human donors were examined using high-resolution structured illumination microscopy (HR-SIM) and laser scanning microscopy (LSM). Autofluorescent granules were analyzed regarding AF phenotype and absolute number of granules. In addition, total AF intensity per cell and granule density (number of granules per cell area) were determined. For the final analysis, RPE cells with total granule number below 5th or above the 95th percentile, or a total AF intensity ± 1.5 standard deviations above or below the mean were included, and compared to the average RPE cell at the same location. Data are presented as mean ± standard deviation.
Results: Within 420 RPE cells examined, 42 cells were further analyzed due to extremes regarding total granule numbers. In addition, 20 RPE cells had AF 1.5 standard deviations below, 28 RPE cells above the mean local AF intensity. Melanolipofuscin granules predominate in RPE cells with low granule content and low AF intensity. RPE cells with high granule content have nearly twice (1.8 times) as many granules as an average RPE cell.
Conclusions: In normal eyes, outliers regarding autofluorescent granule load and AF intensity signals are rare among RPE cells, suggesting that granule deposition and subsequent AF follows intrinsic control mechanisms at a cellular level. The AF of a cell is related to the composition of intracellular granule types. Ongoing studies using AMD donor eyes will examine possible disease related changes in granule distribution and further put lipofuscin′s role in aging and AMD further into perspective.
