Henle fibre layer haemorrhage: clinical features and pathogenesis.

BACKGROUND: To describe the clinical presentation and characteristic imaging features of deep retinal haemorrhages primarily located in the Henle fibre layer (HFL) of the macula. The spectrum of aetiologies and a comprehensive theory of pathogenesis are presented. METHODS: This is a retrospective, multicentre case series evaluating eyes with retinal haemorrhage in HFL. Clinical features, underlying aetiology, systemic and ocular risk factors, visual acuity, and multimodal imaging including fundus photography and cross-sectional and en face optical coherence tomography (OCT) are presented. RESULTS: Retinal haemorrhages localised to HFL in 33 eyes from 23 patients were secondary to acute blunt trauma to the head (n=2), eye (n=1) and trunk (n=1), ruptured intracranial aneurysm (Terson's syndrome, n=3), general anaesthesia (n=1), epidural anaesthesia (n=1), hypertension with anaemia (n=1), decompression retinopathy (n=1), postvitrectomy with intraocular gas (n=1), retinal vein occlusion (n=7), myopic degeneration (n=2), macular telangiectasia type 2 (n=1), and polypoidal choroidal vasculopathy (n=1). Defining clinical features included deep retinal haemorrhage with feathery margin and petaloid pattern radiating from the fovea. OCT demonstrated characteristic hyper-reflectivity from the haemorrhage delineated by obliquely oriented fibres in the Henle layer. Spontaneous resolution of HFL haemorrhage occurred after 3 months in 15 patients with follow-up. CONCLUSION: The characteristic petaloid-shaped, deep intraretinal haemorrhage with a feathery margin localised to HFL is associated with various disorders. The terminology 'Henle fiber layer hemorrhage (HH)' is proposed to describe the clinical and OCT findings, which may result from abnormal retinal venous pressure from systemic or local retinovascular disorders affecting the deep capillary plexus or from choroidal vascular abnormalities.

The long-term effects of anti-vascular endothelial growth factor therapy on the optical coherence tomography angiographic appearance of neovascularization in age-related macular degeneration.

BACKGROUND: The short-term effects of anti-vascular endothelial growth factor (anti-VEGF) treatment on macular neovascularization (MNV) morphology is well described, but long-term studies on morphologic changes and correlation of such changes to the type of MNV have not been conducted. This study aims to determine if different types of MNVs in neovascular AMD (nAMD) behave differently with anti-VEGF treatment as visualized on optical coherence tomography angiography (OCTA). METHODS: Treatment-naïve nAMD patients were retrospectively screened for baseline and follow-up OCTA imaging 10 or more months after initial treatment. Images were graded for MNV type, area, activity, mature versus immature vessels, vessel density, presence of atrophy, atrophy location and area. Growth rate was calculated as the percent change in lesion area from baseline over the years of follow-up. In addition, the occurrence of complete regression and the percent of lesions that grew, remained stable, and shrunk per type was also evaluated. RESULTS: Forty-three eyes from 43 patients with a mean follow-up of 2 years were evaluated. On structural OCT, 26 lesions were classified as pure type 1 MNVs, 12 MNVs had a type 2 component, and 5 MNVs had a type 3 component. Of these cases, 2 mixed-type MNVs were considered to have completely regressed. There was no significant differences in MNV area and growth rate between type 1 and type 2 lesions, but all cases of type 3 lesions shrunk in the follow-up period. There was no correlation between the number of injections per year and growth rate, endpoint MNV area or endpoint activity status for any MNV type. There was no significant association between the development of atrophy and the number of injections, baseline MNV area, baseline vessel density, or lesion growth rate. CONCLUSIONS: In nAMD, complete regression of an MNV network exposed to anti-VEGF is rare. This work emphasizes the role of anti-VEGF as anti-leakage rather than vascular regression agents in nAMD.

Bilateral Myelinated Retinal Nerve Fibers Associated With Bilateral Vitreous Cysts and Solitary Vasoproliferative Tumor: A New Syndrome.

The authors report a case of a 57-year-old male with high myopia, extensive bilateral myelination of the retinal nerve fiber layer, bilateral vitreous cysts, and a solitary vasoproliferative tumor in the right eye. He underwent pars plana vitrectomy and multiple transpupillary thermotherapy treatments for recurrent vitreous hemorrhages and subretinal exudation from the vasoproliferative tumor. To the authors' knowledge, this is the first description of this constellation of findings and suggests this represents a new syndrome. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:356-359.].

Optical Coherence Tomography Angiography Findings in Coats' Disease.

BACKGROUND AND OBJECTIVE: To describe optical coherence tomography angiography (OCTA) findings in patients with unilateral Coats' disease. PATIENTS AND METHODS: Retrospective, observational case series of four patients with unilateral Coats' disease who underwent bilateral OCTA imaging. RESULTS: Bilateral macular OCTA findings of eight eyes are described. An abnormal foveal avascular zone (FAZ) with inner retinal vessels traversing the avascular zone in the superficial capillary plexus was visible on OCTA in the affected eye of all four patients. A similarly abnormal FAZ was noted on OCTA in the clinically normal fellow eye in two of the four patients (50%). CONCLUSION: OCTA may demonstrate an abnormal foveal avascular zone in both the affected eye and the clinically unaffected fellow eye, suggesting widespread pathology of the retinal vasculature in Coats' disease. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:632-635.].

Subconjunctival Bevacizumab for the Treatment of Keratoprosthesis-Associated Cystoid Macular Edema.

The authors present a case of keratoprosthesis-associated cystoid macular edema (CME) responsive to subconjunctival bevacizumab (Avastin; Genentech, South San Francisco, CA). A 40-year-old woman with a history of Stevens-Johnson syndrome (SJS) and Boston keratoprosthesis type I implantation developed CME 10 months after surgery and received sub-Tenon's kenalog with minimal improvement. Sixteen months after surgery, she received a subconjunctival injection of bevacizumab and demonstrated visual and anatomic improvement. Ten weeks later, she received a second subconjunctival injection of bevacizumab for worsening CME and again demonstrated a favorable response. Subconjunctival bevacizumab may be an effective and less-invasive alternative to intravitreal injections for the treatment of postoperative CME.

CHARACTERIZING THE EFFECT OF ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY ON TREATMENT-NAIVE CHOROIDAL NEOVASCULARIZATION USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To use optical coherence tomography angiography (OCTA) to characterize the effects of anti-VEGF injections on treatment-naive choroidal neovascularization (CNV). METHODS: From August 2014 to May 2015, treatment-naive eyes with CNV were scanned using a prototype OCTA system on a commercially available SD-OCT device (Optovue Inc, Fremont, CA). Optical coherence tomography angiography scans were obtained before anti-VEGF injection and at follow-up visits. The CNV area and greatest linear dimension (GLD) were measured along with the maximum retinal pigment epithelial detachment (RPED) height. Changes in subretinal and/or intraretinal fluid were also assessed. RESULTS: Six eyes of six patients with treatment-naive CNV were included. Diagnoses included neovascular age-related macular degeneration, idiopathic polypoidal choroidal vasculopathy, CNV secondary to central serous chorioretinopathy and multifocal choroiditis, and macular telangiectasia Type 2 with subretinal neovascularization. After treatment, all patients with fluid on OCT initially showed a decrease in the amount of fluid. Five of six patients demonstrated decreases in CNV GLD and area with an average reduction of 23.6% and 29.8% respectively. CONCLUSION: Both CNV greatest linear dimension and area measured using OCTA decreased after anti-VEGF treatment in most patients. Optical coherence tomography angiography may be a useful tool for monitoring and quantifying the response of CNV to treatment.

Spectral-domain optical coherence tomography of sympathetic ophthalmia with Dalen-Fuchs nodules.

The authors present a case of sympathetic ophthalmia with Dalen-Fuchs nodules visualized with spectral-domain optical coherence tomography (SD-OCT). An 84-year-old man presented with floaters and decreased vision 25 years after penetrating trauma to the fellow eye. Examination revealed vitritis and subretinal lesions consistent with Dalen-Fuchs nodules. He was diagnosed with sympathetic ophthalmia after a negative systemic work-up. SD-OCT revealed hyper-reflective lesions at the level of the retinal pigment epithelium with disruption of the inner segment/outer segment (IS/OS) junction. Treatment resulted in clinical improvement and disappearance of Dalen-Fuchs nodules on SD-OCT; however, photoreceptor and retinal pigment epithelial disruptions persisted 5 months after treatment was initiated.

Plekhg4 is a novel Dbl family guanine nucleotide exchange factor protein for rho family GTPases.

Mutations in the PLEKHG4 (puratrophin-1) gene are associated with the heritable neurological disorder autosomal dominant spinocerebellar ataxia. However, the biochemical functions of this gene product have not been described. We report here that expression of Plekhg4 in the murine brain is developmentally regulated, with pronounced expression in the newborn midbrain and brainstem that wanes with age and maximal expression in the cerebellar Purkinje neurons in adulthood. We show that Plekhg4 is subject to ubiquitination and proteasomal degradation, and its steady-state expression levels are regulated by the chaperones Hsc70 and Hsp90 and by the ubiquitin ligase CHIP. On the functional level, we demonstrate that Plekhg4 functions as a bona fide guanine nucleotide exchange factor (GEF) that facilitates activation of the small GTPases Rac1, Cdc42, and RhoA. Overexpression of Plekhg4 in NIH3T3 cells induces rearrangements of the actin cytoskeleton, specifically enhanced formation of lamellopodia and fillopodia. These findings indicate that Plekhg4 is an aggregation-prone member of the Dbl family GEFs and that regulation of GTPase signaling is critical for proper cerebellar function.

Regulation of proto-oncogenic dbl by chaperone-controlled, ubiquitin-mediated degradation.

The dbl proto-oncogene product is a prototype of a growing family of guanine nucleotide exchange factors (GEFs) that stimulate the activation of small GTP-binding proteins from the Rho family. Mutations that result in the loss of proto-Dbl's amino terminus produce a variant with constitutive GEF activity and high oncogenic potential. Here, we show that proto-Dbl is a short-lived protein that is kept at low levels in cells by efficient ubiquitination and degradation. The cellular fate of proto-Dbl is regulated by interactions with the chaperones Hsc70 and Hsp90 and the protein-ubiquitin ligase CHIP, and these interactions are mediated by the spectrin domain of proto-Dbl. We show that CHIP is the E3 ligase responsible for ubiquitination and proteasomal degradation of proto-Dbl, while Hsp90 functions to stabilize the protein. Onco-Dbl, lacking the spectrin homology domain, cannot bind these regulators and therefore accumulates in cells at high levels, leading to persistent stimulation of its downstream signaling pathways.