The Relationship of the Clinical Disc Margin and Bruch's Membrane Opening in Normal and Glaucoma Subjects.

PurposeWe tested the hypotheses that the mismatch between the clinical disc margin (CDM) and Bruch's membrane opening (BMO) is a function of BMO area (BMOA) and is affected by the presence of glaucoma.MethodsA total of 45 normal eyes (45 subjects) and 53 glaucomatous eyes (53 patients) were enrolled and underwent radial optic nerve head (ONH) imaging with spectral domain optical coherence tomography. The inner tip of the Bruch's membrane (BM) and the clinical disc margin were marked on radial scans and optic disc photographs, and were coregistered with custom software. The main outcome measure was the difference between the clinical disc area (CDA) and BMOA, or CDA-BMOA mismatch, as a function of BMOA and diagnosis. Multivariate regression analyses were used to explore the influence of glaucoma and BMOA on the mismatch.ResultsGlobal CDA was larger than BMOA in both groups but the difference was statistically significant only in the normal group (1.98 ± 0.37 vs. 1.85 ± 0.45 mm2, P = 0.02 in the normal group; 1.96 ± 0.38 vs. 1.89 ± 0.56 mm2, P = 0.08 in the glaucoma group). The sectoral CDA-BMOA mismatch was smaller in superotemporal (P = 0.04) and superonasal (P = 0.05) sectors in the glaucoma group. The normalized CDA-BMOA difference decreased with increasing BMOA in both groups (P < 0.001). Presence or severity of glaucoma did not affect the CDA-BMOA difference (P > 0.14).ConclusionsClinical disc area was larger than BMOA in normal and glaucoma eyes but reached statistical significance only in the former group. The CDA-BMOA mismatch diminished with increasing BMOA but was not affected by presence of glaucoma. These findings have important clinical implications regarding clinical evaluation of the ONH

Distinguishing wet from dry age-related macular degeneration using three-dimensional computer-automated threshold Amsler grid testing

Background/aims: With the increased efficacy of current therapy for wet age-related macular degeneration (AMD), better ways to detect wet AMD are needed. This study was designed to test the ability of three-dimensional contrast threshold Amsler grid (3D-CTAG) testing to distinguish wet AMD from dry AMD. Methods: Conventional paper Amsler grid and 3D-CTAG tests were performed in 90 eyes: 63 with AMD (34 dry, 29 wet) and 27 controls. Qualitative comparisons were based upon the three-dimensional shapes of central visual field (VF) defects. Quantitative analyses considered the number and volume of the three-dimensional defects. Results: 25/34 (74%) dry AMD and 6/29 (21%) wet AMD eyes had no distortions on paper Amsler grid. Of these, 5/25 (20%) dry and 6/6 (100%) wet (p=0.03) AMD eyes exhibited central VF defects with 3D-CTAG. Wet AMD displayed stepped defects in 16/28 (57%) eyes, compared with only 2/34 (6%) of dry AMD eyes (p=0.002). All three volumetric indices of VF defects were two- to four-fold greater in wet than dry AMD (p<0.006). 3D-CTAG had 83.9% positive and 90.6% negative predictive values for wet AMD. Conclusions: 3D-CTAG has a higher likelihood of detecting central VF defects than conventional Amsler grid, especially in wet AMD. Wet AMD can be distinguished from dry AMD by qualitative and quantitative 3D-CTAG criteria. Thus, 3D-CTAG may be useful in screening for wet AMD, quantitating disease severity, and providing a quantitative outcome measure of therapy

Microperimetry and multimodal imaging in polypoidal choroidal vasculopathy

Polypoidal choroidal vasculopathy (PCV) is a degenerative macular disease. The study determined the topographical concordance in the areal extent of PCV, defined by indocyanine green angiography (ICGA), and the corresponding outcomes from spectral-domain optical coherence tomography (SD-OCT) and microperimetry, in 25 individuals (25 eyes) who had undergone 3 months of anti-vascular endothelial growth factor treatment. The differential light sensitivity within 10° eccentricity was evaluated by Pattern Deviation probability analysis. The concordances and proportional areal extents of the abnormality for ICGA, SD-OCT and microperimetry were compared. The concordance in the areal extent between all three modalities was 59%. The median concordance between ICGA and microperimetry was 60%; between ICGA and SD-OCT, 70%; and between SD-OCT and microperimetry, 72%. SD-OCT and microperimetry each identified a greater areal extent (>20%) compared to ICGA in 13 and 19 eyes, respectively. A greater areal extent (>20%) was present in 9 eyes for microperimetry compared to SD-OCT and in 5 eyes for SD-OCT compared to microperimetry. SD-OCT and microperimetry each identified a greater area of abnormality than ICGA which supports the clinical utility of SD-OCT. Strong concordance was present between SD-OCT and microperimetry; however, microperimetry identified additional areas of functional abnormality

Genome-wide screening of mouse knockouts reveals novel genes required for normal integumentary and oculocutaneous structure and function.

Oculocutaneous syndromes are often due to mutations in single genes. In some cases, mouse models for these diseases exist in spontaneously occurring mutations, or in mice resulting from forward mutatagenesis screens. Here we present novel genes that may be causative for oculocutaneous disease in humans, discovered as part of a genome-wide screen of knockout-mice in a targeted single-gene deletion project. The International Mouse Phenotyping Consortium (IMPC) database (data release 10.0) was interrogated for all mouse strains with integument abnormalities, which were then cross-referenced individually to identify knockouts with concomitant ocular abnormalities attributed to the same targeted gene deletion. The search yielded 307 knockout strains from unique genes with integument abnormalities, 226 of which have not been previously associated with oculocutaneous conditions. Of the 307 knockout strains with integument abnormalities, 52 were determined to have ocular changes attributed to the targeted deletion, 35 of which represent novel oculocutaneous genes. Some examples of various integument abnormalities are shown, as well as two examples of knockout strains with oculocutaneous phenotypes. Each of the novel genes provided here are potentially relevant to the pathophysiology of human integumentary, or oculocutaneous conditions, such as albinism, phakomatoses, or other multi-system syndromes. The novel genes reported here may implicate molecular pathways relevant to these human diseases and may contribute to the discovery of novel therapeutic targets

Pachychoroid neovasculopathy and age-related macular degeneration.

Pachychoroid neovasculopathy is a recently proposed clinical entity of choroidal neovascularization (CNV). As it often masquerades as neovascular age-related macular degeneration (AMD), it is currently controversial whether pachychoroid neovasculopathy should be distinguished from neovascular AMD. This is because its characteristics have yet to be well described. To estimate the relative prevalence of pachychoroid neovasculopathy in comparison with neovascular AMD and to investigate the phenotypic/genetic differences of the two diseases, we evaluated 200 consecutive Japanese patients who agreed to participate in the genetic study and diagnosed with pachychoroid neovasculopathy or neovascular AMD. Pachychoroid neovasculopathy was observed in 39 individuals (19. 5%), which corresponds to one fourth of neovascular AMD. Patients with pachychoroid neovasculopathy were significantly younger (p = 5. 1 × 10[−5]) and showed a greater subfoveal choroidal thickness (p = 3. 4 × 10[−14]). Their genetic susceptibility to AMD was significantly lower than that of neovascular AMD; ARMS2 rs10490924 (p = 0. 029), CFH rs800292 (p = 0. 013) and genetic risk score calculated from 11 AMD susceptibility genes (p = 3.8 × 10[−3]). Current results implicate that the etiologies of the two conditions must be different. Thus, it will be necessary to distinguish these two conditions in future studie

Multidimensional en-face OCT imaging of the retina.

Fast T-scanning (transverse scanning, en-face) was used to build B-scan or C-scan optical coherence tomography (OCT) images of the retina. Several unique signature patterns of en-face (coronal) are reviewed in conjunction with associated confocal images of the fundus and B-scan OCT images. Benefits in combining T-scan OCT with confocal imaging to generate pairs of OCT and confocal images similar to those generated by scanning laser ophthalmoscopy (SLO) are discussed in comparison with the spectral OCT systems. The multichannel potential of the OCT/SLO system is demonstrated with the addition of a third hardware channel which acquires and generates indocyanine green (ICG) fluorescence images. The OCT, confocal SLO and ICG fluorescence images are simultaneously presented in a two or a three screen format. A fourth channel which displays a live mix of frames of the ICG sequence superimposed on the corresponding coronal OCT slices for immediate multidimensional comparison, is also included. OSA ISP software is employed to illustrate the synergy between the simultaneously provided perspectives. This synergy promotes interpretation of information by enhancing diagnostic comparisons and facilitates internal correction of movement artifacts within C-scan and B-scan OCT images using information provided by the SLO channel

Focal choroidal excavation in eyes with central serous chorioretinopathy.

[Purpose]To study the prevalence and 3-dimensional (3-D) tomographic features of focal choroidal excavations in eyes with central serous chorioretinopathy (CSC) using swept-source optical coherence tomography (OCT). [Design]Prospective, cross-sectional study. [Methods]We examined 116 consecutive eyes with CSC with a prototype 3-D swept-source OCT. 3-D images of the shape of the macular area, covering 6 × 6 mm2, were reconstructed by segmentation of the outer surface of the retinal pigment epithelium (RPE). [Results]The 3-D swept-source OCT detected focal choroidal excavations in 9 eyes (7.8%). The 3-D scanning protocol, coupled with en face scans, allowed for clear visualization of the excavation morphology. In 5 eyes with focal excavations, unusual choroidal tissue was found beneath the excavation, bridging the bottom of the excavation and the outer choroidal boundary. Additionally, 3 of those 5 eyes showed a suprachoroidal space below the excavation, as if the outer choroidal boundary is pulled inward by this bridging tissue. The focal choroidal excavations were located within fluorescein leakage points and areas of choroidal hyperpermeability. Eyes with focal choroidal excavations were more myopic (−4.42 ± 2.92 diopters) than eyes without excavations (−0.27 ± 1.80 diopters, P = .001). Subfoveal choroidal thickness was significantly thinner (301.3 ± 60.1 μm) in eyes with focal excavations than in eyes without the excavations (376.6 ± 104.8 μm, P = .036). [Conclusions]Focal choroidal excavations were present in 7.8% of eyes with CSC. In these eyes, focal choroidal excavations may have formed from RPE retraction caused by focal scarring of choroidal connective tissue

Assessing Photoreceptor Structure Associated with Ellipsoid Zone Disruptions Visualized with Optical Coherence Tomography

Purpose: To compare images of photoreceptor layer disruptions obtained with optical coherence tomography (OCT) and adaptive optics scanning light ophthalmoscopy (AOSLO) in a variety of pathologic states.Methods: Five subjects with photoreceptor ellipsoid zone disruption as per OCT and clinical diagnoses of closed-globe blunt ocular trauma (n = 2), macular telangiectasia type 2 (n = 1), blue-cone monochromacy (n = 1), or cone-rod dystrophy (n = 1) were included. Images were acquired within and around photoreceptor lesions using spectral domain OCT, confocal AOSLO, and split-detector AOSLO.Results: There were substantial differences in the extent and appearance of the photoreceptor mosaic as revealed by confocal AOSLO, split-detector AOSLO, and spectral domain OCT en face view of the ellipsoid zone.Conclusion: Clinically available spectral domain OCT, viewed en face or as B-scan, may lead to misinterpretation of photoreceptor anatomy in a variety of diseases and injuries. This was demonstrated using split-detector AOSLO to reveal substantial populations of photoreceptors in areas of no, low, or ambiguous ellipsoid zone reflectivity with en face OCT and confocal AOSLO. Although it is unclear if these photoreceptors are functional, their presence offers hope for therapeutic strategies aimed at preserving or restoring photoreceptor function

Assessment of macular choroidal thickness by optical coherence tomography and angiographic changes in central serous chorioretinopathy.

[Objective]: To investigate the relationship between macular choroidal thickness measured by highpenetrating swept-source optical coherence tomography (SS-OCT) and angiographic findings in central serous chorioretinopathy (CSC). [Design]: Prospective cross-sectional case series. [Participants and Controls]: Thirty-four patients with CSC (44 eyes) and 17 volunteer subjects (17 normal eyes). [Methods]: All subjects underwent a comprehensive ophthalmologic and SS-OCT prototype examination. All patients with CSC also underwent simultaneous fluorescein angiography (FA) and indocyanine green angiography (IA). Mean regional choroidal thickness measurements on the Early Treatment Diabetic Retinopathy Study (ETDRS) layout and squared sector grids were obtained by 3-dimensional raster scanning using SS-OCT. [Main Outcome Measures]: Macular choroidal thickness and angiographic abnormalities. [Results]: Mean whole macular choroidal thickness in eyes with CSC (total, 329.3_83.0 _m; classic CSC, 326.9_83.1 _m; chronic CSC, 325.4_93.3 _m; and multifocal posterior pigment epitheliopathy, 359.0_15.5 _m) was greater than that in normal eyes (233.0_67.0_m) (P_ 0.001). In unilateral cases, mean whole macular choroidal thickness was greater in eyes with unilateral CSC than in unaffected fellow eyes (P_0.021). There was no significant difference in choroidal thickness between active eyes and resolved eyes in any of the ETDRS sectors. Mean choroidal thickness was greater in areas with leakage on FA than in areas without leakage (P_0.001). Mean choroidal thickness was greater in areas with choroidal vascular hyperpermeability and in areas with punctate hyperfluorescent spots on IA than in unaffected areas (P_0.001 for both). [Conclusions]: Increased choroidal thickness was observed in the whole macular area of eyes with any of the CSC subtypes. Choroidal thickness was related to leakage from the retinal pigment epithelium, choroidal vascular hyperpermeability, and punctate hyperfluorescent lesions. These findings provide evidence that CSC may be caused by focally increased hydrostatic pressure in the choroid. [Financial Disclosure(s)]: Proprietary or commercial disclosure may be found after the references