scholarly journals Closing the Gap: Mechanisms of Epithelial Fusion During Optic Fissure Closure

Author(s):  
Brian Ho Ching Chan ◽  
Mariya Moosajee ◽  
Joe Rainger

A key embryonic process that occurs early in ocular development is optic fissure closure (OFC). This fusion process closes the ventral optic fissure and completes the circumferential continuity of the 3-dimensional eye. It is defined by the coming together and fusion of opposing neuroepithelia along the entire proximal-distal axis of the ventral optic cup, involving future neural retina, retinal pigment epithelium (RPE), optic nerve, ciliary body, and iris. Once these have occurred, cells within the fused seam differentiate into components of the functioning visual system. Correct development and progression of OFC, and the continued integrity of the fused margin along this axis, are important for the overall structure of the eye. Failure of OFC results in ocular coloboma—a significant cause of childhood visual impairment that can be associated with several complex ocular phenotypes including microphthalmia and anterior segment dysgenesis. Despite a large number of genes identified, the exact pathways that definitively mediate fusion have not yet been found, reflecting both the biological complexity and genetic heterogeneity of the process. This review will highlight how recent developmental studies have become focused specifically on the epithelial fusion aspects of OFC, applying a range of model organisms (spanning fish, avian, and mammalian species) and utilizing emerging high-resolution live-imaging technologies, transgenic fluorescent models, and unbiased transcriptomic analyses of segmentally-dissected fissure tissue. Key aspects of the fusion process are discussed, including basement membrane dynamics, unique cell behaviors, and the identities and fates of the cells that mediate fusion. These will be set in the context of what is now known, and how these point the way to new avenues of research.

Author(s):  
Feng He ◽  
Melina A. Agosto ◽  
Ralph M. Nichols ◽  
Theodore G. Wensel

AbstractThe low-abundance lipid phosphatidylinositol-3-phosphate (PI(3)P) is important for membrane dynamics in autophagy, endosome processing, and phagocytosis. In retinal pigmented epithelial cells (RPE) all three pathways are important, but phagocytosis of disk membranes shed from adjacent photoreceptors is especially important for ensuring health of photoreceptors and preventing retinal degeneration. By eliminating Vps34, the kinase responsible for synthesizing PI(3)P in RPE, we have found that PI(3)P plays distinct roles in each pathway. In phagocytosis it is not required for disk engulfment or phagosome transport but is essential for recruitment and lipidation of LC3. In contrast, initiation of autophagy and LC3 recruitment to autophagosomes does not require PI(3)P, which can be bypassed by an alternative mechanism of ATG16L recruitment that does not require PI(3)P, Rab11a, or WIPI2. In all three pathways, PI(3)P is essential for fusion with lysosomes; autophagosomes, phagosomes, and Rab7-positive late endosomes, as well as enlarged lysosomes, accumulate in large numbers in the absence of Vps34, leading to cell death.


2014 ◽  
Vol 2014 ◽  
pp. 1-3 ◽  
Author(s):  
Firat Helvacioglu ◽  
Ziya Kapran ◽  
Sadik Sencan ◽  
Murat Uyar ◽  
Ozlem Cam

Importance.There is a conflict about the content of the macular folds in nanophthalmic eyes in the literature. Our study clearly demonstrated that papillomacular folds seen in nanophthalmos or posterior microphthalmos were only composed of neurosensory retina without involvement of retinal pigment epithelium and choroid.Observations.This is a report of two consecutive nanophthalmic patients with macular folds at Maltepe University School of Medicine, Department of Ophthalmology, from January to June 2012. Anterior segment dimensions were near normal. The axial lengths of the eyes were short with markedly shortened posterior segment. A macular fold extending from the center of the fovea towards the optic nerve head was present in all eyes. Optic coherence tomography clearly demonstrated that folds were only composed of neurosensory retina. Binocular visual acuities and refractive errors of the cases were 0.3, 0.2 and +16.00, +15.75 diopters, respectively.Conclusions and Relevance.Our study proposes a surgical option to treat these folds like serous retinal detachments by showing the true content of the folds, although there is not any surgical operation accepted for this condition yet. Further studies dealing with the surgical interventions of these folds should be performed to support this option.


2003 ◽  
Vol 13 (5) ◽  
pp. 496-499 ◽  
Author(s):  
K. Erkiliç ◽  
A. Özkiriş ◽  
C. Evereklioglu ◽  
H. Dogan

Purpose To report a case of Rieger anomaly associated with bilateral choroidal osteoma. CASE. An 18-year-old woman presented with corectopia, iridocorneal adhesions, and stromal hypoplasia of the iris, and was diagnosed with Rieger anomaly. Results Fundus examination revealed bilateral yellowish-orange, placoid degenerative fundus lesions with pseudopod-like edges associated with the areas of retinal pigment epithelium atrophy, indicating choroidal osteoma. Fundus fluorescein angiography showed bilateral early patchy and late diffuse hyperfluorescence. B-scan echography revealed placoid lesion at the posterior ocular coats characterized by localized areas of high ultrasound reflectivity with a corresponding retrobulbar orbital shadowing. This indicated a dense calcium foreign body. In addition, computed tomography of the orbit demonstrated bilateral plate-like thickening with calcification of the choroid that was isodense with the normal skeletal bone. Conclusions Although Rieger anomaly is classically known as a disease of the anterior segment of the eye, choroidal osteoma may be a posterior segment finding of the disease that has not previously been reported.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ine Lambert ◽  
Giuseppe Fasolino ◽  
Gil Awada ◽  
Robert Kuijpers ◽  
Marcel ten Tusscher ◽  
...  

Abstract Background The use of immunomodulating therapy to treat various cancers has been on the rise and these immune checkpoint inhibitors are known to cause ocular side effects. In this article a case of acute exudative polymorphous vitelliform maculopathy (AEPVM) is reported which developed during a first line treatment with pembrolizumab. Case presentation A 54-year-old woman was referred because of blurry vision in both eyes with a yellow spot in the central visual field of the left eye. These symptoms started after four treatments with pembrolizumab (a monoclonal antibody against the programmed cell death receptor-1) for a metastatic recurrent vaginal mucosal melanoma. Her best corrected visual acuity was 10/10 in both eyes with a correction of + 2.00 bilaterally. There were no inflammatory findings in the anterior segment or the vitreous. Fundoscopy revealed an attenuation of the foveal reflex with subtle yellow-white subretinal macular deposits (vitelliform lesions) in both eyes. Fluorescein angiography did not show staining or leakage in the mid-phase, neither a late staining. Spectral-domain optical coherence tomography of the macula illustrated bilateral neurosensory retinal detachment with a thick, highly reflective band at the outer photoreceptor segment. En face structural OCT at the level of the photoreceptors showed focal areas of increased signal corresponding to hyperreflective vitelliform material. The treatment with pembrolizumab was ceased immediately. During the following visits we slowly saw an improvement of the neurosensory retinal detachment. After almost four months a total resolution of the subretinal fluid was visualized in both eyes without the use of additional treatment, though the vitelliform deposits persisted. Conclusions The development of AEPVM in melanoma patients could be triggered by treatment with Pembrolizumab. Pembrolizumab has the potential to disturb indirectly the retinal pigment epithelium homeostasis with accumulation of lipofuscin deposits and subretinal fluid, both signs of AEPVM.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ílen Ferreira Costa ◽  
Livia Pimenta Bonifácio ◽  
Fernando Bellissimo-Rodrigues ◽  
Eduardo Melani Rocha ◽  
Rodrigo Jorge ◽  
...  

AbstractTo describe the medium-term ophthalmological findings in patients recovering from COVID-19. Patients recovered from the acute phase of COVID-19 underwent a complete ophthalmological evaluation, including presenting and best-corrected visual acuity (BCVA), refractometry, biomicroscopy, tonometry, break-up time and Schirmer tests, indirect ophthalmoscopy, color fundus picture, and retinal architecture evaluation using optical coherence tomography. Socio-demographic data and personal medical history were also collected. According to the severity of systemic manifestations, patients were classified into mild-to-moderate, severe, and critical. Sixty-four patients (128 eyes) were evaluated 82 ± 36.4 days after the onset of COVID’s symptoms. The mean ± SD duration of hospitalization was 15.0 ± 10.7 days. Seven patients (10.9%) had mild-to-moderate, 33 (51.5%) severe, and 24 (37.5%) critical disease. Median [interquartile ranges (IQR)] presenting visual acuity was 0.1 (0–0.2) and BCVA 0 (0–0.1). Anterior segment biomicroscopy was unremarkable, except for dry eye disease, verified in 10.9% of them. The mean ± SD intraocular pressure (IOP) in critical group (14.16 ± 1.88 mmHg) was significantly higher than in severe group (12.51 ± 2.40 mmHg), both in the right (p 0.02) and left eyes (p 0.038). Among all, 15.6% had diabetic retinopathy, and two patients presented with discrete white-yellowish dots in the posterior pole, leading to hyporreflective changes at retinal pigment epithelium level, outer segment, and ellipsoid layers. The present study identified higher IOP among critical cases, when compared to severe cases, and discrete outer retina changes 80 days after COVID-19 infection. No sign of uveitis was found.


2021 ◽  
Vol 8 (04) ◽  
pp. 224-229
Author(s):  
Arvind Babu ◽  
Narayanan Balakrishnan ◽  
Uma Maheshwari ◽  
Praveena V ◽  
Dharssana Periyathambi

BACKGROUND Serpiginous choroiditis (SC) is an intraocular inflammatory disorder displaying a geographic pattern of choroiditis, extending from the juxtapapillary choroid and intermittently spreading centrifugally. It involves the overlying retinal pigment epithelium (RPE), the outer retina including the choriocapillaries and the choroid.1,2,3 Infectious diseases like tuberculous (TB) uveitis, herpes simplex virus (HSV) uveitis whose fundus changes mimic SC are termed as serpiginous-like choroidopathy (SLC). On slit lamp examination, anterior segment usually appears quiet, non-granulomatous anterior uveitis with mild vitritis and / or fine pigmented cells within the vitreous can be seen. The pattern of fundus involvement varies between the two groups. Fundus fluorescein angiography and indocyanine green angiography (FFA and ICG) are important modalities of investigation that help in differentiating the pattern of involvement and confirming clinical findings. The duration of follow up, reactivation of lesions and complications vary. Hence, it is important to differentiate between SC and SLC for proper diagnosis and appropriate management. The aim of this study is to highlight important features of serpiginous choroiditis and serpiginous like choroidopathy that will aid in the correct diagnosis of these two entities. METHODS This is a retrospective study of 40 patients. Following variables were analysed - age, gender, laterality, visual acuity, and intraocular inflammation through slit lamp examination, pattern of involvement, choroidal-neovascularization, reactivation, clinical investigations and diagnosis. RESULTS 32 patients had serpiginous choroiditis (SC) and eight patients had serpiginous like choroiditis (SLC). Mean age was 50 and 51 years (SC and SLC respectively). Males were predominantly affected (65.5 % in serpiginous choroiditis and 62.5 % in serpiginous like choroiditis). Bilaterality was 80 % in SC-group and 46 % in the SLC-group. Vitreous haze was lesser than or equal to 1 + in SC group. The juxtapapillary-area was involved in 90 % in SC eyes and 0 % in SLC-group. Midperiphery of fundus was involved in 54 % of SLC-group. Reactivation is more common in SLC group than in SC group in a follow up period of one year. Choroidal-neovascularisation was found in two patients only in SLC-group. CONCLUSIONS In cases where vitreous haze is greater than 1 + with unilateral involvement and disease free peripapillary area is present, an infectious aetiology has to be strongly suspected, as an immunomodulatory therapy could have severe consequences. KEYWORDS Serpiginous Choroiditis, Serpiginous like Choroiditis, Autoimmune


2015 ◽  
Vol 2015 ◽  
pp. 1-5
Author(s):  
Georges Azar ◽  
Romain Leze ◽  
Aude Affortit-Demoge ◽  
Céline Faure

Objectives. To demonstrate the usefulness of “en-face” Spectral Domain Optical Coherence Tomography (SD-OCT) combined with Fluorescein Angiography (FA) in the investigation of peripapillary intrachoroidal cavitation.Materials and Methods. A 72-year-old man followed for primary open-angle glaucoma (POAG) for 4 years was referred for an asymptomatic “peripapillary lesion.” A full ophthalmological examination and conventional imaging of the retina were done. FA, Indocyanine Green Angiography (ICG-A), and SD-OCT using the “en-face” technique were also performed.Results. Best-corrected visual acuity (BCVA) was 20/25 both eyes. Slit-lamp examination revealed no abnormalities of anterior segment. Intraocular pressure (IOP) was normal. Fundus examination showed a triangular yellow-orange thickening at the inferior border of both optic nerves. FA showed early hypofluorescence of the lesion and progressive staining without any dye pooling. SD-OCT with “en-face” technique showed an intrachoroidal hyporeflective space resembling a cavitation below the retinal pigment epithelium (RPE).Conclusions. “En-face” SD-OCT and FA are valuable techniques for the diagnosis of peripapillary intrachoroidal cavitation associated with myopia. Pathophysiological insights regarding SD-OCT findings and angiography behavior are offered.


2021 ◽  
Vol 14 (3) ◽  
pp. e239556
Author(s):  
Ashish Markan ◽  
Bruttendu Moharana ◽  
Mohit Dogra ◽  
Ramandeep Singh

A 47-year-old man presented to our retina clinic with gradual onset diminution of vision in his right eye for the last 3 months. Anterior segment evaluation was normal in both eyes. Fundus evaluation showed the presence of leopard spot appearance in the right eye with inferior exudative retinal detachment. Multimodal imaging was done to evaluate retinal pigment epithelium function, choroidal thickness, choroidal vascularity and scleral thickness. Multimodal imaging showed increased choroidal thickness, choroidal congestion on indocyanine green angiography and peripheral choroidal detachment with normal sclera thickness in our patient, thus pointing towards a diagnosis of uveal effusion syndrome type 3.


2021 ◽  
pp. 1-3
Author(s):  
Katja Göbel

To describe the medium-term ophthalmological findings in patients recovering from COVID-19. Patients recovered from the acute phase of COVID-19 underwent a complete ophthalmological evaluation, including presenting and best-corrected visual acuity (BCVA), refractometry, biomicroscopy, tonometry, break-up time and Schirmer tests, indirect ophthalmoscopy, color fundus picture, and retinal architecture evaluation using optical coherence tomography. Socio-demographic data and personal medical history were also collected. According to the severity of systemic manifestations, patients were classified into mild-to-moderate, severe, and critical. Sixty-four patients (128 eyes) were evaluated 82 ± 36.4 days after the onset of COVID’s symptoms. The mean ± SD duration of hospitalization was 15.0 ± 10.7 days. Seven patients (10.9%) had mild-to-moderate, 33 (51.5%) severe, and 24 (37.5%) critical disease. Median [interquartile ranges (IQR)] presenting visual acuity was 0.1 (0–0.2) and BCVA 0 (0–0.1). Anterior segment biomicroscopy was unremarkable, except for dry eye disease, verified in 10.9% of them. The mean ± SD intraocular pressure (IOP) in critical group (14.16 ± 1.88 mmHg) was significantly higher than in severe group (12.51 ± 2.40 mmHg), both in the right (p 0.02) and left eyes (p 0.038). Among all, 15.6% had diabetic retinopathy, and two patients presented with discrete white-yellowish dots in the posterior pole, leading to hyporreflective changes at retinal pigment epithelium level, outer segment, and ellipsoid layers. The present study identified higher IOP among critical cases, when compared to severe cases, and discrete outer retina changes 80 days after COVID-19 infection. No sign of uveitis was found.


Intraocular inflammations are still a diagnostic challenge for ophthalmologists. It is often difficult to make a precise etiological diagnosis in certain situations. Ancillary investigations are very useful in diagnosing the pathologies and monitoring inflammation in the anterior as well as the posterior segment. The most commonly used ancillary investigations in noninfectious uveitis include laser flare meter for anterior segment inflammation, fundus fluorescein angiography (FA) for retinal diseases, indocyanine green angiography (ICGA) for choroidal pathologies, fundus autofluorescence (FAF) for retinal pigment epithelium (RPE) and optical coherence tomography (OCT) as well as ultrasonography for the posterior segment. Laboratory investigations in the diagnosis of noninfectious uveitis are also very important, This review aims to be an overview describing the role of commonly used investigations.


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