An update on the ophthalmic features in hereditary haemorrhagic telangiectasia (Rendu-Osler-Weber syndrome)

Hereditary haemorrhagic telangiectasia (HHT) or Osler-Rendu-Weber syndrome is a rare autosomal dominant disease, characterised by systemic angiodysplasia. Dysfunction of the signalling pathway of β transforming growth factor is the main cause of HHT principally owing to mutations of the genes encoding for endoglin (ENG) and activin A receptor type II-like 1 (ACVRL1). Clinical manifestations can range from mucocutaneous telangiectasia to organ arterio-venous malformations and recurrent epistaxis. The early clinical manifestations may sometimes be subtle, and diagnosis may be delayed. The main ophthalmic manifestations historically reported in HHT are haemorrhagic epiphora, and conjunctival telangiectasia present in 45–65% of cases, however, imaging with wide-field fluorescein angiography has recently shown peripheral retinal telangiectasia in 83% of patients. Optimal management of HHT requires both understanding of the clinical presentations and detection of early signs of disease. Advances in imaging methods in ophthalmology such as wide-field fluorescein angiography, spectral domain optical coherence tomography, and near infrared reflectance promise further insight into the ophthalmic signs of HHT towards improved diagnosis and early management of possible severe complications.

Fluorescein Leakage and Optical Coherence Tomography Angiography Features of Microaneurysms in Diabetic Retinopathy

Background and Objective. To correlate optical coherence tomography angiography (OCTA) characteristics of diabetic microaneurysms (MAs) with leakage status on fluorescein angiography (FA). Patients and Methods. 167 MAs from 39 diabetic eyes were analyzed using OCTA and FA simultaneously. The characteristics of MAs on OCTA en face, OCT en face, and OCT B-scan with flow overlay were evaluated and correlated with fluorescein leakage status. Results. Thirty-six, fifty-two, and seventy-nine MAs showed no, mild, and severe leakage on FA, respectively. Most MAs (61.7%) were centered in the inner nuclear layer. Cystoid spaces were observed adjacent to 60 (35.9%) MAs. MAs with severe leakage had a statistically higher flow proportion compared to MAs with no or mild leakage (both P < 0.001 ). Only 112 MAs (67.1%) were visualized in the OCTA en face images, while 165 MAs (98.8%) could be visualized in the OCT en face images. The location of MAs did not associate significantly with FA leakage status. The presence of nearby cystoid spaces and higher flow proportion by OCT B-scan with flow overlay correlated significantly with FA leakage status. Conclusion. The flow proportion of MAs observed on OCT B-scans with flow overlay might be a potential biomarker to identify leaking MAs. A combination of OCT B-scan, OCT en face, and OCTA en face images increased the detection rate of diabetic MAs in a noninvasive way.

Blocking Ocular Sympathetic Activity Inhibits Choroidal Neovascularization

Purpose: To investigate how modulating ocular sympathetic activity affects progression of choroidal neovascularization (CNV), a hallmark feature of wet age-related macular degeneration (AMD).Methods: In the first of two studies, Brown Norway rats underwent laser-induced CNV and were assigned to one of the following groups: daily eye drops of artificial tears (n = 10; control group); daily eye drops of the β-adrenoreceptor agonist isoproterenol (n = 10); daily eye drops of the β-adrenoreceptor antagonist propranolol (n = 10); sympathetic internal carotid nerve (ICN) transection 6 weeks prior to laser-induced CNV (n = 10). In the second study, rats underwent laser-induced CNV followed by ICN transection at different time points: immediately after the laser injury (n = 6), 7 days after the laser injury (n = 6), and sham surgery 7 days after the laser injury (n = 6; control group). All animals were euthanized 14 days after laser application. CNV development was quantified with fluorescein angiography and optical coherence tomography (in vivo), as well as lesion volume analysis using 3D confocal reconstruction (postmortem). Angiogenic growth factor protein levels in the choroid were measured with ELISA.Results: In the first study, blocking ocular sympathetic activity through pharmacological or surgical manipulation led to a 75% or 70% reduction in CNV lesion volume versus the control group, respectively (P &lt; 0.001). Stimulating ocular sympathetic activity with isoproterenol also led to a reduction in lesion volume, but only by 27% versus controls (P &lt; 0.05). VEGF protein levels in the choroid were elevated in the three treatment groups (P &lt; 0.01). In the second study, fluorescein angiography and CNV lesion volume analysis indicated that surgically removing the ocular sympathetic supply inhibited progression of laser-induced CNV, regardless of whether ICN transection was performed on the same day or 7 days after the laser injury.Conclusion: Surgical and pharmacological block of ocular sympathetic activity can inhibit progression of CNV in a rat model. Therefore, electrical block of ICN activity could be a potential bioelectronic medicine strategy for treating wet AMD.

Neovascular Glaucoma Associated with Chronic Rhegmatogenous Retinal Detachment

Background To demonstrate the clinical features and natural course of chronic retinal detachment associated neovascular glaucoma. Methods Ten patients, diagnosed with chronic retinal detachment-associated neovascular glaucoma during 2007-2016 were retrospectively investigated. Besides chronic retinal detachment, no patients had any neovascular glaucoma-predisposing conditions, such as carotid artery disease. Retinal perfusion status was evaluated from postoperative visual acuity, intraocular pressures, ocular examination findings, and fluorescein angiography images. Results The mean age of patients was 57.5 (range: 22-78) years. Complete retinal reattachment was achieved in 3 eyes, while partial or total chronic retinal detachment persisted in 7 eyes. Wide-angle fundus fluorescein angiography revealed peripheral retinal capillary obstruction and severe non-perfusion. Neovascular glaucoma developed 213.4 months (17-634 months) after retinal detachment. Three eyes received Ahmed valve implantation, while 5 eyes received intravitreal bevacizumab injection. Intraocular pressure was controlled in 10 eyes. Two eyes developed phthisis bulbi during follow-up. Conclusions In eyes with a chronic retinal detachment history, iris neovascularization and neovascular glaucoma can develop due to retinal capillary obstruction and chronic retinal ischemia, even after achieving retinal reattachment. We suggest routine follow-up examinations for patients with chronic retinal detachment, particularly for eyes with retinal non-perfusion, as detected on fundus fluorescein angiography.

Evaluation of the role of fundus fluorescein angiography and spectral domain-optical coherence tomography in choroidal neo-vascularization: a hospital-based study

Background: The study was conducted to evaluate the role of fundus fluorescein angiography (FFA) and spectral domain-optical coherence tomography (SD-OCT) in choroidal neo-vascularisation (CNV).Methods: This was a hospital based prospective study carried out in the post-graduate department of ophthalmology, SKIMS medical college, Bemina, Srinagar, Jammu and Kashmir. All patients diagnosed with CNV fulfilling the criteria during the study period w.e.f. October 2018 to March 2020 were enrolled. Visual acuity and pinhole test using Snellen’s chart for literate and E chart for illiterate patient, slit lamp biomicroscope for anterior segment examination, ophthalmoscopy, including stereoscopic examination of the posterior pole, 90D examination of the fundus, Intra-ocular pressure measurement, FFA and SD-OCT was done in these patients.Results: Diagnostic accuracy of OCT was observed with a sensitivity 79.1% (95% confidence interval (CI): 67.3-90.7), specificity 84.3% (95% CI: 74.5-92.9), positive and negative predictive values 78.7% and 85.4%, respectively, (95% CI: 65.5-95.6) and (74.8-93.4) and diagnostic accuracy of FFA was observed with a sensitivity 81.4% (95% confidence interval (CI): 70.6-93.5), specificity 82.31% (95% CI: 71.9-89.3), positive and negative predictive values 79.9% and 83.7%, respectively, (95% CI: 68.8-92.9) and (70.3-91.2).Conclusions: FFA is the gold standard procedure for screening ARMD and detection of dry ARMD, but OCT is more specific diagnostic tool in detecting early subretinal neovascular membrane and also to assess the extent, location and activity of the neovascular membranes. This study concludes that SDOCT is highly sensitive for identifying AMD, CNV, and CNV activity and due to its non-invasive nature with no adverse effects and less time consuming can be used as 1st line of diagnostic modality and FFA be reserved for cases where SD-OCT is not helpful.

Retinal Occlusive Vasculitis in a Patient with Hyperimmunoglobulin E Syndrome

Background. Hyperimmunoglobulin E syndrome (HIES), or Job’s syndrome, is a primary immunodeficiency disorder that is characterized by an elevated level of IgE with values reaching over 2000 IU ( normal < 200 IU ), eczema, and recurrent staphylococcus infection. Affected individuals are predisposed to infection, autoimmunity, and inflammation. Herein, we report a case of HIES with clinical findings of retinal occlusive vasculitis. Case Presentation. A 10-year-old boy with a known case of hyperimmunoglobulin E syndrome had exhibited loss of vision and bilateral dilated fixed pupil. Fundoscopic examination revealed peripheral retinal hemorrhaging, vascular sheathing around the retinal arteries and veins, and vascular occlusion in both eyes. A fluorescein angiography of the right eye showed hyper- and hypofluorescence in the macula and hypofluorescence in the periphery of the retina, peripheral arterial narrowing, and arterial occlusion. A fluorescein angiography of the left eye showed hyper- and hypofluorescence in the supranasal area of the optic disc. Macular optical coherence tomography of the right eye showed inner and outer retinal layer distortion. A genetic study was performed that confirmed mutations of the dedicator of cytokinesis 8 (DOCK 8). HSV polymerase chain reaction testing on aqueous humor and vitreous was negative, and finally, the patient was diagnosed with retinal occlusive vasculitis. Conclusion. Occlusive retinal vasculitis should be considered as a differential diagnosis in patients with hyperimmunoglobulin E syndrome presenting with visual loss.

Ultra-Widefield Fluorescein Angiography Image Brightness Compensation Based on Geometrical Features

Ultra-widefield fluorescein angiography (UWFA) is an emerging imaging modality used to characterise pathologies in the retinal vasculature, such as microaneurysms (MAs) and vascular leakages. Despite its potential value for diagnosis and disease screening, objective quantitative assessment of retinal pathologies by UWFA is currently limited because laborious manual processing is required. In this report, we describe a geometrical method for uneven brightness compensation inherent to UWFA imaging technique. The correction function is based on the geometrical eyeball shape, therefore it is fully automated and depends only on pixel distance from the center of the imaged retina. The method’s performance was assessed on a database containing 256 UWFA images with the use of several image quality measures that show the correction method improves image quality. The method is also compared to the commonly used CLAHE approach and was also employed in a pilot study for vascular segmentation, giving a noticeable improvement in segmentation results. Therefore, the method can be used as an image preprocessing step in retinal UWFA image analysis.

Combining Feature Correspondence with Parametric Chamfer Alignment: Hybrid Two-Stage Registration for Ultra-Widefield Retinal Images

<div>We propose a novel hybrid framework for registering retinal images in the presence of extreme geometric distortions that are commonly encountered in ultra-widefield (UWF) fluorescein angiography. Our approach consists of two stages: a feature-based global registration and a vessel-based local refinement. For the global registration, we introduce a modified RANSAC algorithm that jointly identifies robust matches between feature keypoints in reference and target images and estimates a polynomial geometric transformation consistent with the identified correspondences. Our RANSAC modification particularly improves feature point matching and the registration in peripheral regions that are most severely impacted by the geometric distortions. The second local refinement stage is formulated in our framework as a parametric chamfer alignment for vessel maps obtained using a deep neural network. Because the complete vessel maps contribute to the chamfer alignment, this approach not only improves registration accuracy but also aligns with clinical practice, where vessels are typically a key focus of examinations. We validate the effectiveness of the proposed framework on a new UWF fluorescein angiography (FA) dataset and on the existing narrow-field FIRE (fundus image registration) dataset and demonstrate that it significantly outperforms prior retinal image registration methods. The proposed approach enhances the utility of large sets of longitudinal UWF images by enabling: (a) automatic computation of vessel change metrics and (b) standardized and co-registered examination that can better highlight changes of clinical interest to physicians.</div>