Spatially resolved imaging of human macular capillaries using adaptive optics-enhanced optical coherence tomography angiography.

Documenting the organization of the retinal capillaries is of importance to understand the visual consequences of vascular diseases which may differentially affect the microvascular layers. Here we detailed the spatial organization of the macular capillaries in ten healthy human subjects using a prototypic adaptive optics-enhanced optical coherence tomography angiography (AO-OCTA) system. Within the central 6° × 6°, the radial peripapillary capillaries and the superficial, intermediate and deep vascular plexuses (SVP, IVP and DVP, respectively) were consistently resolved. In 8 out of the 10 eyes, the capillary segments composing the perifoveal arcade (PFA) were perfused only by the SVP, while drainage of the PFA showed more variability, comprising a case in which the PFA was drained by the DVP. Around the center, a distinct central avascular zone could be documented for each layer in 7 of the 10 cases; in three eyes, the IVP and SVP merged tangentially around the center. In all eyes, the foveal avascular zone was larger in the DVP than in the SVP and IVP. In one eye with incomplete separation of the inner foveal layers, there was continuity of both the SVP and the IVP; a central avascular zone was only present in the DVP. The diversity of perfusion and drainage patterns supported a connectivity scheme combining parallel and serial organizations, the latter being the most commonly observed in perifoveal vessels. Our results thus help to further characterize the diversity of organization patterns of the macular capillaries and to robustly analyze the IVP, which will help to characterize early stages of microvascular diseases.

Characterization of retinal arteries by adaptive optics ophthalmoscopy image analysis.

OBJECTIVE: This paper aims at quantifying biomarkers from the segmentation of retinal arteries in adaptive optics ophthalmoscopy images (AOO). METHODS: The segmentation is based on the combination of deep learning and knowledge-driven deformable models to achieve a precise segmentation of the vessel walls, with a specific attention to bifurcations. Biomarkers (junction coefficient, branching coefficient, wall to lumen ratio (wlr) are derived from the resulting segmentation. RESULTS: reliable and accurate segmentations (mse = 1.75 ± 1.24 pixel) and measurements are obtained, with high reproducibility with respect to images acquisition and users, and without bias. SIGNIFICANCE: In a preliminary clinical study of patients with a genetic small vessel disease, some of them with vascular risk factors, an increased wlr was found in comparison to a control population. CONCLUSION: The wlr estimated in AOO images with our method (AOV, Adaptive Optics Vessel analysis) seems to be a very robust biomarker as long as the wall is well contrasted.

[Subfoveal posterior ciliary arteries: Multimodal imaging and classification based on choroidal elevation]. / Artères ciliaires postérieures sous-maculaires : imagerie multimodale et classification basée sur l'importance du soulèvement choroïdien.

PURPOSE: To characterize the magnitude and consequences for interpretation of macular elevations associated with short posterior ciliary arteries (SPCA) extending to the fovea. METHODS: Retrospective study of 96 eyes of 138 patients who underwent multimodal imaging (color photographs, SD-OCT with OCT-angiography analysis, fluorescein angiography [FA] and indocyanine green angiography [ICG]) over a two-year period. The authors selected patients with a focal choroidal elevation (FCE) associated with a SPCA extending to the fovea. FCEs were classified according to their magnitude as "Low" (<50µm), "Medium" (50µm to 100µm) and "High" (>100µm). RESULTS: Ten patients aged 80.10±11.82 years had a FCE associated with a macular SPCA. The patients were followed for advanced AMD with neovascularization (2 cases), advanced AMD with geographic atrophy (3 cases), intermediate AMD (1 case) ; one patient was followed for diabetes ; three patients had no identified retinal pathology. The FCE associated with the SPCAs was Low (3 cases), Medium (2 cases), High (3 cases). In 2 cases, the FCE was limited to an unmeasurable choroidal fold. The interpretation associated with these FCEs was not always related to the magnitude of the elevation. CONCLUSION: Our observations show the value of multimodal imaging in the identification of SPCA extending to the fovea, sometimes associated with a macular FCE. In some cases, the signs associated with FCE interfered with the monitoring of the condition for which the patient was being followed. Identifying these FCEs and grading their amplitude is relevant, as they should not be confused with pathological structures.

[Role of the lamina cribrosa in the pathogenesis of glaucoma. A review of the literature]. / Rôle de la lame criblée dans la pathogenèse du glaucome. Une revue de la littérature.

Located within the scleral canal, the lamina cribrosa is a sieve-like structure separating the intraocular and retrobulbar portions of the optic nerve. Identified as the main site of axonal damage in glaucomatous optic neuropathy, the study of the lamina cribrosa has been of great interest for many years. Numerous studies have explored the histological and morphological characteristics of the laminar region in healthy subjects as well as glaucoma patients. More recently, the development of adaptive optics systems and new generations of OCT has allowed great progress in the understanding of the pathogenesis of glaucoma and has opened new perspectives for the improvement of diagnostic procedures.

Immediate post partum macular subretinal bleeding in a highly myopic patient: a case report.

BACKGROUND: Pathologic myopia is a major cause of visual impairment and blindness. CASE PRESENTATION: We report a case of an immediate post partum macular subretinal bleeding observed in a highly myopic patient. A 30-years-old woman presented two days after childbirth for sudden loss of vision in her right eye. Multimodal imaging showed macular hemorrhage masking a subtle yellowish linear lesion corresponding to lacker crack. Due to the lack of evidence for choroidal neovascularization, a simple clinical and imaging monitoring was recommended. Six weeks later, we noted an improvement in her best-corrected visual acuity and a decreased in size of the macular hemorrhage. CONCLUSIONS: This is the first case reporting a macular subretinal bleeding on macular lacquer cracks in a highly myopic patient in immediate post partum. Valsalva maneuver associated with vaginal delivery could explain the occurrence of the hemorrhage associated with lacquer crack. However, natural history of pathological myopia could not be excluded.

Reversible corneal stromal thinning, acute-onset white cataract and angle-closure glaucoma due to erdafitinib, a fibroblast growth factor receptor inhibitor: Report of three cases.

PURPOSE: To report corneal and lens toxicity in patients undergoing chemotherapy with erdafitinib, a fibroblast growth factor receptor (FGFR) inhibitor. METHODS: This retrospective case series contains three patients from a cohort of 41 patients receiving erdafitinib, a selective pan-FGFR inhibitor, for chemotherapy. These three patients underwent complete ophthalmic examination: one was followed by corneal topography and the other two were followed by anterior segment optical coherence tomography. RESULTS: All three patients had severe dry eye syndrome. One patient had bilateral corneal thinning. One patient had bilateral neurosensory retinal detachment, unilateral corneal thinning and white cataracts in both eyes. The third patient had bilateral corneal thinning, a corneal ulcer of the left eye and acute-onset white cataracts in both eyes, causing angle-closure glaucoma in the left eye. Following the cessation of erdafitinib treatment or a decrease in the dose used, corneal thinning resolved in all three cases within four months. Acute-onset cataracts were treated urgently by surgery, with no complications. In one patient, although the corneal ulcer healed, corneal transparency was lost, and the patient never fully recovered his initial vision. CONCLUSION: Bilateral neurosensory retinal detachment associated with FGFR inhibitor use has already been reported. However, we provide herein the first report of reversible corneal thinning and acute-onset white cataracts causing angle-closure glaucoma associated with FGFR inhibitor use. Early recognition and management of these adverse ocular reactions are required to prevent vision loss due to acute glaucoma and/or corneal ulcer.

In vivo laser Doppler holography of the human retina.

The eye offers a unique opportunity for the non-invasive exploration of cardiovascular diseases. Optical angiography in the retina requires sensitive measurements, which hinders conventional full-field laser Doppler imaging schemes. To overcome this limitation, we used digital holography to perform laser Doppler perfusion imaging of human retina with near-infrared light. Two imaging channels with a slow and a fast CMOS camera were used simultaneously for real-time narrowband measurements, and offline wideband measurements, respectively. The beat frequency spectrum of optical interferograms recorded with the fast (up to 75 kHz) CMOS camera was analyzed by short-time Fourier transformation. Power Doppler images drawn from the Doppler power spectrum density qualitatively revealed blood flow in retinal vessels over 512 × 512 pixels covering 2.4 × 2.4 mm2 on the retina with a temporal resolution down to 1.6 ms. The sensitivity to lateral motion as well as the requirements in terms of sampling frequency are discussed.

[Retinal vein occlusions]. / Occlusions veineuses rétiniennes.

Retinal venous occlusions comprise central retinal vein occlusion, hemiretinal vein occlusions, and branch retinal vein occlusions. They are associated with arterial hypertension and glaucoma. Retinal vein occlusions occur more frequently in males, at a median age of 55. The pathogenesis of retinal venous occlusions remains obscure. The clinical presentation of the disease is variable. In most cases, there is a unilateral visual loss over days with a painless, white and quiet eye. However, retinal venous occlusions may also present as an abrupt and profound loss of vision, or be asymptomatic. The course of the disease may be chronic, often with exacerbations. The most severe complication is the onset of extensive capillary non-perfusion, with a high risk of neovascular glaucoma. The most frequent complication is macular edema due to breakdown of the blood-retinal barrier, which can originate from the macula itself and/or from the disc. The treatment is symptomatic. Retinal venous occlusions may resolve either because of the recanalization of the affected vein, or because of the establishment of an efficient collateral circulation. Intravitreal anti-VEGF antibodies or steroids may transiently improve vision, as well as laser photocoagulation, focused or not on macroaneurysms. Visual sequelae are frequent.

High speed optical holography of retinal blood flow.

We performed noninvasive video imaging of retinal blood flow in a pigmented rat by holographic interferometry of near-infrared laser light backscattered by retinal tissue, beating against an off-axis reference beam sampled at a frame rate of 39 kHz with a high throughput camera. Local Doppler contrasts emerged from the envelopes of short-time Fourier transforms and the phase of autocorrelation functions of holograms rendered by Fresnel transformation. This approach permitted imaging of blood flow in large retinal vessels (∼30 microns diameter) over 400×400 pixels with a spatial resolution of ∼8 microns and a temporal resolution of ∼6.5 ms.

Retinal arteriolar remodeling evaluated with adaptive optics camera: Relationship with blood pressure levels.

AIM: To research a retinal arterioles wall-to-lumen ratio or lumen diameter cut-off that would discriminate hypertensive from normal subjects using adaptive optics camera. PATIENTS AND METHODS: One thousand and five hundred subjects were consecutively recruited and Adaptive Optics Camera rtx1™ (Imagine-Eyes, Orsay, France) was used to measure wall thickness, internal diameter, to calculate wall-to-lumen ratio (WLR) and wall cross-sectional area of retinal arterioles. Sitting office blood pressure was measured once, just before retinal measurements and office blood pressure was defined as systolic blood pressure>=140mmHg and diastolic blood pressure>=90mmHg. ROC curves were constructed to determine cut-off values for retinal parameters to diagnose office hypertension. In another population of 276 subjects office BP, retinal arterioles evaluation and home blood pressure monitoring were obtained. The applicability of retinal WLR or diameter cut-off values were compared in patients with controlled, masked, white-coat and sustained hypertension. RESULTS: In 1500 patients, a WLR>0.31 discriminated office hypertensive subjects with a 0.57 sensitivity and 0.71 specificity. Lumen diameter<78.2µm discriminated office hypertension with a 0.73 sensitivity and a 0.52 specificity. In the other 276 patients, WLR was higher in sustained hypertension vs normotensive patients (0.330±0.06 vs 0.292±0.05; P<0.001) and diameter was narrower in masked hypertensive vs normotensive subjects (73.0±11.2 vs 78.5±11.6µm; P<0.005). CONCLUSION: A WLR higher than 0.31 is in favour of office arterial hypertension; a diameter under<78µm may indicate a masked hypertension. Retinal arterioles analysis through adaptive optics camera may help the diagnosis of arterial hypertension, in particular in case of masked hypertension.

In vivo characterization of lamina cribrosa pore morphology in primary open-angle glaucoma.

PURPOSE: To characterize the in vivo morphology of human lamina cribrosa pores in healthy and glaucoma eyes. PATIENTS AND METHODS: In this cross-sectional, observational study, a flood-illumination adaptive optics fundus (FIAO) camera was used to perform in vivo, high-resolution, noninvasive imaging of the optic disc and lamina cribrosa in 30 patients diagnosed with primary open-angle glaucoma (POAG), in 15 healthy controls and in 14 healthy subjects with at least one direct relative with POAG. Two masked graders measured each visible lamina cribrosa pore along the major and minor axes in order to categorize pores as oval (minor/major axis ratio<0.75) or round. We used these same measurements to calculate pore surface area as a best-fit oval. RESULTS: Lamina cribrosa pores were visible in 95.2% of the subjects. In 52% of controls, the pores were visualized under the neuroretinal rim. In POAG patients, 78% of visible pores had an oval shape versus 19.4% in controls (P<0.01). Average pore surface area was significantly different (1561 px(2) versus 724 px(2); P<0.01). In healthy subjects with at least one direct relative with POAG, 21% had pores with an appearance comparable to that of subjects in the glaucoma group. CONCLUSION: On average, lamina cribrosa pores are elongated in POAG eyes and also in healthy eyes of POAG relatives. In vivo characterization of lamina cribrosa pore morphology by FIAO imaging may enhance our understanding of glaucoma, and offer new means for its early detection.

[Spontaneous separation of epiretinal membrane: Reports of 3 cases]. / Pelage spontané de membrane épimaculaire : série de 3 cas.

PURPOSE: Idiopathic epiretinal membranes most commonly develop in patients over 50 years of age. Posterior vitreous detachment seems to play a role in their formation. Epiretinal membranes are uncommon in young subjects. Surgical intervention is indicated in eyes with true functional symptoms and loss of visual acuity. METHOD: We report 3 cases with spontaneous separation of epiretinal membranes imaged by Optical Coherence Tomography. RESULTS: All patients reported improvement in functional symptoms after spontaneous separation of the epiretinal membrane. Anatomic recovery with reappearance of the foveolar depression was observed on Optical Coherence Tomography. CONCLUSION: A longer period of observation may be indicated in young patients with epiretinal membrane, due to the higher rate of spontaneous separation.

Three-dimensional structure of the mammalian limbal stem cell niche.

Although the existence of the limbal stem cell (LSC) niche is accepted, precise knowledge of its three-dimensional (3D) architecture remains incomplete. The LSC niche was explored on freshly excised and organ-cultured corneoscleral rims from human donors (n = 47), pigs (n = 15) and mice (n = 27) with full-field optical coherence microscopy (FFOCM). Limbal crypt features were detected in 90% of organ-cultured human corneoscleral rims, extending between the palisades of Vogt as radially oriented rectangular (74% of eyes) and/or rounded (23% of eyes) forms, often branching off to, or becoming interconnected by, sub-scleral radially or circumferentially oriented crypts (in 56% of eyes). Mean crypt volume represented 16% of sampled limbal volume on the vertical axis and 8% on the horizontal axis. In pigs, palisades were finer and crypts wider with relatively uniform distribution around the eye, and radial orientation, connecting to numerous narrow criss-crossing invaginations beneath the scleral surface. In mice, only a circumferential limbal trough was detected. Mean crypt volume represented 13% of sampled limbal volume in humans and 9% in pigs. FFOCM combined with fluorescence, and confocal fluorescence microscopy, showed presence of p63-α+ cells and cytokeratin-3+ cells in the limbal crypts. To assess colony forming efficiency (CFE), limbal epithelial cells were cultured at low density with mitomycin-arrested 3T3 feeders. CFE increased with limbal crypt volume and was not significantly decreased in organ-cultured cornea, despite degradation of the epithelial roof, suggesting that stem cells remain protected at the base of crypts during organ culture. CFE in human samples was significantly greater than in pig, and CFE in mouse was zero. Crypt architecture in the three species appears associated with eye exposure to light. LSC density increased with percentage limbal volume occupied by crypts.

Surgical management of dysthyroid diplopia with preservation of the anterior ciliary vascularization: review of ten cases.

PURPOSE: During the surgical correction of dysthyroid diplopia, the risk of ischemia by transection of the anterior ciliary arteries is well-known. In order to avoid this, we modified the classical surgical technique: (1) through the preservation of the vascular pedicles during muscle recession and (2) if necessary, through a plication (instead of a resection) of the ipsilateral antagonist muscle. The objective to be achieved is thus the resolution of the diplopia without ischemic complications. SUBJECTS AND METHODS: We report a prospective series of 10 patients with dysthyroid ophthalmopathy, causing strabismic diplopia, all operated on by the same surgeon (BR) after at least 12 months of euthyroidism. Data collection included: history of previous decompressive surgery, surgical procedure, and oculomotor status before and after surgery. RESULTS: Ten patients (8 females), aged 51 to 74 years (mean age, 58.00 ± 7.62 years), were collected between 2008 and 2012. All patients had one or more vascular risk factors (diabetes, smoking, obesity, high blood pressure). With a follow-up from 16 to 67 months (mean ± SD 27.7 months ± 14.87), surgical outcomes were excellent: diplopia was cured in all cases, with recovery of stereoscopic vision. We had no operative or postoperative complications. CONCLUSIONS: The technique of preservation of the anterior ciliary vascularization, which is particularly justified for these fragile patients, is compatible with moderate muscle recessions. For larger deviations, in which a larger recession might increase the proptosis, it is possible to add a plication of the ipsilateral antagonist. This surgical technique made possible the suppression of the diplopia in all cases.

Holographic laser Doppler imaging of microvascular blood flow.

We report on local superficial blood flow monitoring in biological tissue from laser Doppler holographic imaging. In time-averaging recording conditions, holography acts as a narrowband bandpass filter, which, combined with a frequency-shifted reference beam, permits frequency-selective imaging in the radio frequency range. These Doppler images are acquired with an off-axis Mach-Zehnder interferometer. Microvascular hemodynamic components mapping is performed in the cerebral cortex of the mouse and the eye fundus of the rat with near-infrared laser light without any exogenous marker. These measures are made from a basic inverse-method analysis of local first-order optical fluctuation spectra at low radio frequencies, from 0 Hz to 100 kHz. Local quadratic velocity is derived from Doppler broadenings induced by fluid flows, with elementary diffusing wave spectroscopy formalism in backscattering configuration. We demonstrate quadratic mean velocity assessment in the 0.1-10 mm/s range in vitro and imaging of superficial blood perfusion with a spatial resolution of about 10 micrometers in rodent models of cortical and retinal blood flow.

[Imaging of retinal arteries with adaptative optics, feasibility and reproducibility]. / Imagerie des artérioles rétiniennes par optique adaptative, faisabilité et reproductibilité.

OBJECTIVE: Adaptative optic is a new non-invasive imaging technique that allows to measure arterioles wall thickness and diameter with a resolution near two microns. Our objectives were to evaluate the feasibility and the reproducibility of this technique in untreated hypertensive patients. DESIGN AND METHODS: In 23 naive hypertensive patients and in 14 normotensives, the internal diameter (ID) and the wall thickness of the superior temporal artery were automatically measured. Those measurements were made on a temporal artery segment and led to determine a whole vessel cross sectional area (WCSA) and a wall to lumen ratio (WLR). Intra-observer reproducibility was evaluated by realizing three consecutive measurements in 14 subjects. Inter-observer reproducibility was assessed by two independent readers in 17 patients. Variation coefficient was calculated as SD/mean values. A comparison of retinal parameters was made between normal and hypertensive subjects. RESULTS: Inter-observer reproducibility indicated a variation coefficient of 1.3% for ID, 3.7% for the WCSA and 3.2% for the WLR. Intra-observer reproducibility indicated a variation coefficient of 3.2% for the WLR. Arterial remodeling was present in hypertensive patients at baseline with a significantly increased WLR as compared to normal subjects (0.32 ± 0.04 vs. 0.26 ± 0.04; P<0.05), both population having the same ID. CONCLUSION: Adaptative optics is feasible and reproducible technique. The possibility of a direct and non-invasive assessment of retinal arterioles must assess the attractions in this technique in hypertensive patients' care.