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.

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.

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.

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.

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.

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.

[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.

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.

Holographic laser Doppler ophthalmoscopy.

We report laser Doppler ophthalmoscopic fundus imaging in the rat eye with near-IR heterodyne holography. Sequential sampling of the beat of the reflected radiation against a frequency-shifted optical local oscillator is made onto an array detector. Wide-field maps of fluctuation spectra in the 10 Hz to 25 kHz band exhibit angiographic contrasts in the retinal vascular tree without requirement of an exogenous marker.

Macular pattern dystrophy in MIDD: long-term follow-up.

A case of maternally inherited diabetes and deafness (MIDD)-associated macular pattern dystrophy with a 15-year follow-up is reported. On initial examination at age 37, visual acuity was normal, but chorioretinal atrophy at the posterior pole was already present in both eyes. At age 52, visual acuity remained normal in the right eye and was only slightly decreased in the left eye despite notable extension of the areas of chorioretinal atrophy in that eye. No evidence of diabetic retinopathy was present at any time. This case shows that visual acuity can remain stable in the long term despite extensive lesions of macular pattern dystrophy.

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.

Subretinal electrode implantation in the P23H rat for chronic stimulations.

BACKGROUND: In age related macular degeneration and inherited dystrophies, preservation of retinal ganglion cells has been demonstrated. This finding has led to the development of various models of subretinal or epiretinal implant in order to restore vision. This study addresses the development of a polyimide subretinal electrode platform in the dystrophic P23H rat in vivo. METHODS: A technique was developed for implanting a subretinal electrode into the subretinal space and stabilising the distal extremity of the cabling on the rat cranium in order to allow future electrical stimulations of the retina. RESULTS: In vivo imaging of the retina with the scanning laser ophthalmoscope demonstrated reabsorption of the surgically induced retinal detachment and the absence of major tissue reactions. These in vivo observations were confirmed by retinal histology. The extraocular fixation system on the rat cranium was effective in stabilising the distal connector for in vivo stimulation. CONCLUSION: This study demonstrates that a retinal implant can be introduced into the subretinal space of a dystrophic rat with a stable external connection for repeatable electrical measurements and stimulation. This in vivo model should therefore allow us to evaluate the safety and efficacy of electrical stimulations on dystrophic retina.

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.

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.

[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.