Focal Scleral Nodule: A New Name for Solitary Idiopathic Choroiditis and Unifocal Helioid Choroiditis.

PURPOSE: To evaluate multimodal imaging findings of solitary idiopathic choroiditis (SIC; also known as unifocal helioid choroiditis) to clarify its origin, anatomic location, and natural course. DESIGN: Multicenter retrospective observational case series. PARTICIPANTS: Sixty-three patients with SIC in 1 eye. METHODS: Demographic and clinical data were collected. Multimodal imaging included color fundus photography, OCT (including swept-source OCT), OCT angiography (OCTA), fundus autofluorescence, fluorescein and indocyanine green angiography, and B-scan ultrasonography. MAIN OUTCOME MEASURES: Standardized grading of imaging features. RESULTS: Mean age at presentation was 56 ± 15 years (range, 12-83 years). Mean follow-up duration in 39 patients was 39 ± 55 months (range, 1 month-25 years). The lesions measured a mean of 2.4 × 2.1 mm in basal diameter, were located inferior (64%) or nasal to the optic disc, and appeared yellow (53%). No systemic associations were found. The lesions all appeared as an elevated subretinal mass, with OCT demonstrating all lesions to be confined to the sclera, not the choroid. On OCT, the deep lesion margin was visible in 12 eyes with a mean lesion thickness of 0.6 mm. Overlying choroidal thinning or absence was seen in 95% (mean choroidal thickness, 28 ± 35 µm). Mild subretinal fluid was observed overlying the lesions in 9 patients (14%). Retinal pigment epithelial disruption and overlying retinal thinning was observed in 56% and 57%, respectively. OCT angiography was performed in 13 eyes and demonstrated associated choroidal and lesional flow voids. Four lesions (6%) were identified at the macula, leading to visual loss in 1 patient. One lesion demonstrated growth and another lesion showed spontaneous resolution. CONCLUSIONS: In this largest series to date, multimodal imaging of SIC demonstrated a scleral location in all patients. The yellow and white clinical appearance may be related to scleral unmasking resulting from atrophy of overlying tissues. Additional associated features included documentation of deep margin on swept-source OCT, trace subretinal fluid in a few patients, and OCTA evidence of lesional flow voids. Because of the scleral location of this lesion in every patient, a new name, focal scleral nodule, is proposed.

SUPERFICIAL AND DEEP CAPILLARY ISCHEMIA AS A PRESENTING SIGN OF RETINAL VASCULOPATHY WITH CEREBRAL LEUKOENCEPHALOPATHY AND SYSTEMIC MANIFESTATIONS.

PURPOSE: The aim of this study was to investigate the presenting sign of retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations, a rare autosomal dominant condition caused by mutations in the TREX1 gene, and to explore the potential efficacy of bevacizumab in preventing capillary occlusions. METHODS: Observational case report with the use of ultra-widefield fluorescein angiography, optical coherence tomography, and optical coherence tomography angiography. RESULTS: A 31-year-old man with a family history of retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations presented with a scotoma in his left eye. The visual acuity was 20/20 in both eyes, and his examination was notable for scattered cotton wool spots in the retina of both eyes as well as an area of paracentral acute middle maculopathy in the left eye. Ultra-widefield fluorescein angiography revealed peripheral capillary nonperfusion and vascular leakage corresponding to the cotton wool spots. Spectral domain optical coherence tomography and optical coherence tomography angiography confirmed the presence and distribution of superficial capillary plexus and deep capillary plexus ischemia. Neurologic examination and imaging were normal. A trial of monthly intravitreal bevacizumab injections to the left eye over 6 months resulted in diminished capillary leakage. CONCLUSION: Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations is a rare genetic condition manifested most commonly by cerebral and retinal ischemia. This retinal vasculopathy leads to occlusions of small-caliber retinal vessels in the superficial plexus and deep plexus with resulting cotton wool spots and paracentral acute middle maculopathy, respectively. Recognition of the retinal findings by ophthalmologists and neurologists may avoid unnecessary brain biopsies in diagnosing this rare disorder.

PERIPAPILLARY PACHYCHOROID SYNDROME.

PURPOSE: To describe the features of peripapillary pachychoroid syndrome (PPS), a novel pachychoroid disease spectrum (PDS) entity. METHODS: Medical records of 31 eyes (16 patients) with choroidal thickening associated with intraretinal and/or subretinal fluid in the nasal macula extending from the disk were reviewed (patients with PPS). Choroidal thickness was compared with 2 age-matched cohorts: typical PDS (17 eyes with central serous chorioretinopathy or pachychoroid neovasculopathy) and 19 normal eyes. RESULTS: The patients with PPS were 81% men aged 71 ± 7 years. Peripapillary pachychoroid syndrome eyes displayed thicker nasal versus temporal macular choroids, unlike PDS eyes with thicker temporal macular choroids (P < 0.0001). Peripapillary intraretinal and/or subretinal fluid was often overlying dilated Haller layer vessels (pachyvessels). Fundus autofluorescence and fluorescein angiography illustrated peripapillary pigmentary mottling without focal leakage. Most PPS eyes (70%) exhibited other PDS findings including serous pigment epithelial detachment or gravitational tracks. Indocyanine green angiography illustrated dilated peripapillary pachyvessels and choroidal hyperpermeability. The disk was usually crowded, with edema noted in 4/31 (13%) eyes and mild late fluorescein disk leakage identified in half of the cases. Choroidal folds (77%), short axial lengths (39% less than 23 mm), and hyperopia (86%) were common. CONCLUSION: Peripapillary pachychoroid syndrome is a distinct PDS variant, in which peripapillary choroidal thickening is associated with nasal macular intraretinal and/or subretinal fluid and occasional disk edema. Recognition of PPS is important to distinguish it from disorders with overlapping features such as posterior uveitis and neuro-ophthalmologic conditions.

Insights Into Epiretinal Membranes: Presence of Ectopic Inner Foveal Layers and a New Optical Coherence Tomography Staging Scheme.

PURPOSE: To describe the presence of continuous ectopic inner foveal layers associated with epiretinal membranes (ERMs) and to present a new optical coherence tomography (OCT) staging system of ERMs. DESIGN: Retrospective multicenter observational case series. METHODS: Clinical charts and spectral-domain OCT images of 194 eyes of 172 consecutive patients diagnosed with ERMs were reviewed and analyzed. RESULTS: The presence of continuous ectopic inner foveal layers was identified in 63 out of 194 eyes (32.5%) and this morphology was significantly associated with lower visual acuity. ERMs were divided into 4 stages. Stage 1 (43 out of 194 eyes, 22.1%) ERMs were mild and thin and a foveal depression was present. Stage 2 (88 out of 194 eyes, 45.4%) ERMs were associated with widening of the outer nuclear layer and loss of the foveal depression. Stage 3 (51 out of 194 eyes, 26.3%) ERMs were associated with continuous ectopic inner foveal layers crossing the entire foveal area. In stages 1, 2, and 3 all retinal layers were clearly defined on OCT. Stage 4 ERMs (12 out of 194 eyes, 6.2%) were thick and associated with continuous ectopic inner foveal layers. In addition, retinal layers were disrupted. Visual acuity progressively declined from stage 1 through stage 4 (P < .001). CONCLUSIONS: The presence of continuous ectopic inner foveal layers in ERMs is a newly described OCT finding associated with significant vision loss and is an essential element of a novel OCT-based grading scheme of ERMs that may influence visual prognosis.

Deformation of Optic Nerve Head and Peripapillary Tissues by Horizontal Duction.

PURPOSE: To ascertain deformation of the optic nerve head (ONH) and peripapillary tissues caused by horizontal duction. DESIGN: Prospective, experimental study. METHODS: Optical coherence tomography of the ONH region was performed in 23 eyes of 12 normal volunteers in central gaze and increasing (10, 20, and 30 degrees) adduction and abduction. Main outcome measures were changes from central gaze in the configuration of the ONH and peripapillary tissues in eccentric gazes. RESULTS: Adduction but not abduction was associated with significant, progressive relative posterior displacement of the temporal peripapillary retinal pigment epithelium (tRPE) from its position in central gaze reaching 49 ± 10 µm in 30-degree adduction (standard error of mean, P < .0001). Absolute (anterior or posterior) optic cup displacement (OCD) averaged 41 ± 7 µm in 30-degree adduction. Linear regression showed significant effect of adduction on absolute OCD (slope 1.09 ± 0.36 µm/degree, P = .0037). In 20-degree and 30-degree adduction, all eyes exhibited significant progressive temporal ONH tilting reaching 3.1 ± 0.4 degrees in 30-degree adduction (P < .0001). Abduction was not associated with significant peripapillary RPE displacement, OCD, or ONH tilt. Both nasal and temporal peripapillary choroid averaged 9-19 µm thinner in adduction and abduction than in central gaze (P < .02). CONCLUSIONS: Adduction temporally tilts and displaces the prelaminar ONH and peripapillary tissues. Both adduction and abduction compress the peripapillary choroid. These effects support magnetic resonance imaging and biomechanical evidence that adduction imposes strain on the ONH and peripapillary tissues. Repetitive strain from eye movements over decades might in susceptible individuals lead to optic neuropathies such as normal tension glaucoma.

ULTRA-WIDEFIELD FUNDUS IMAGING: A Review of Clinical Applications and Future Trends.

PURPOSE: To review the basic principles of ultra-widefield fundus imaging and discuss its clinical utility for a variety of retinal and choroidal disorders. METHODS: A systematic review of the PubMed database was performed using the search terms Optos, optomap, panoramic, ultra-widefield, wide-angle, and ellipsoid mirror. This yielded 158 publications of which 128 were selected based on content and relevance. RESULTS: A total of 128 articles pertaining to ultra-widefield imaging were cited in this review. CONCLUSION: Optos ultra-widefield imaging has become an essential tool for the identification of peripheral retinal and vascular pathology. The high resolution and multimodal capabilities of this device are also providing new insights into a variety of disorders, even those that primarily involve the posterior pole. Although the presence of artifact and the need for clinical validation are significant hurdles to more widespread use, ultra-widefield is evolving to become the standard-of-care imaging modality for many diseases and is finding new clinical and research applications such as for screening and telemedicine.

Autotaxin-lysophosphatidic acid axis is a novel molecular target for lowering intraocular pressure.

Primary open-angle glaucoma is the second leading cause of blindness in the United States and is commonly associated with elevated intraocular pressure (IOP) resulting from diminished aqueous humor (AH) drainage through the trabecular pathway. Developing effective therapies for increased IOP in glaucoma patients requires identification and characterization of molecular mechanisms that regulate IOP and AH outflow. This study describes the identification and role of autotaxin (ATX), a secretory protein and a major source for extracellular lysophosphatidic acid (LPA), in regulation of IOP in a rabbit model. Quantitative proteomics analysis identified ATX as an abundant protein in both human AH derived from non-glaucoma subjects and in AH from different animal species. The lysophospholipase D (LysoPLD) activity of ATX was found to be significantly elevated (by ∼1.8 fold; n=20) in AH derived from human primary open angle glaucoma patients as compared to AH derived from age-matched cataract control patients. Immunoblotting analysis of conditioned media derived from primary cultures of human trabecular meshwork (HTM) cells has confirmed secretion of ATX and the ability of cyclic mechanical stretch of TM cells to increase the levels of secreted ATX. Topical application of a small molecular chemical inhibitor of ATX (S32826), which inhibited AH LysoPLD activity in vitro (by >90%), led to a dose-dependent and significant decrease of IOP in Dutch-Belted rabbits. Single intracameral injection of S32826 (∼2 µM) led to significant reduction of IOP in rabbits, with the ocular hypotensive response lasting for more than 48 hrs. Suppression of ATX expression in HTM cells using small-interfering RNA (siRNA) caused a decrease in actin stress fibers and myosin light chain phosphorylation. Collectively, these observations indicate that the ATX-LPA axis represents a potential therapeutic target for lowering IOP in glaucoma patients.

Periaxin is required for hexagonal geometry and membrane organization of mature lens fibers.

Transparency of the ocular lens depends on symmetric packing and membrane organization of highly elongated hexagonal fiber cells. These cells possess an extensive, well-ordered cortical cytoskeleton to maintain cell shape and to anchor membrane components. Periaxin (Prx), a PDZ domain protein involved in myelin sheath stabilization, is also a component of adhaerens plaques in lens fiber cells. Here we show that Prx is expressed in lens fibers and exhibits maturation dependent redistribution, clustering discretely at the tricellular junctions in mature fiber cells. Prx exists in a macromolecular complex with proteins involved in membrane organization including ankyrin-B, spectrin, NrCAM, filensin, ezrin and desmoyokin. Importantly, Prx knockout mouse lenses were found to be softer and more easily deformed than normal lenses, revealing disruptions in fiber cell hexagonal packing, membrane skeleton and membrane stability. These observations suggest a key role for Prx in maturation, packing, and membrane organization of lens fiber cells. Hence, there may be functional parallels between the roles of Prx in membrane stabilization of the myelin sheath and the lens fiber cell.