Marta Pazos

Rat Optic Nerve Head Anatomy within 3D Histomorphometric Reconstructions of Normal Control Eyes

The purpose of this study is to three-dimensionally (3D) characterize the principal macroscopic and microscopic relationships within the rat optic nerve head (ONH) and quantify them in normal control eyes. Perfusion-fixed, trephinated ONH from 8 normal control eyes of 8 Brown Norway Rats were 3D histomorphometrically reconstructed, visualized, delineated and parameterized. The rat ONH consists of 2 scleral openings, (a superior neurovascular and inferior arterial) separated by a thin connective tissue strip we have termed the scleral sling. Within the superior opening, the nerve abuts a prominent extension of Bruchs Membrane (BM) superiorly and is surrounded by a vascular plexus, as it passes through the sclera, that is a continuous from the choroid into and through the dural sheath and contains the central retinal vein (CRV), (inferiorly). The inferior scleral opening contains the central retinal artery and three long posterior ciliary arteries which obliquely pass through the sclera to obtain the choroid. Bruchs Membrane Opening (BMO) is irregular and vertically elongated, enclosing the nerve (superiorly) and CRV and CRA (inferiorly). Overall mean BMO Depth, BMO Area, Choroidal Thickness and peripapillary Scleral Thickness were 29xa0μm, 56.5xa0×xa010(3)xa0μm(2), 57xa0μm and 104xa0μm respectively. Mean anterior scleral canal opening (ASCO) and posterior scleral canal opening (PSCO) radii were 201xa0±xa015xa0μm and 204xa0±xa016xa0μm, respectively. Mean optic nerve area at the ASCO and PSCO were 46.3xa0×xa010(3)±4.4xa0×xa010(3)xa0μm(2) and 44.1xa0×xa010(3)±4.5xa0×xa010(3)xa0μm(2) respectively. In conclusion, the 3D complexity of the rat ONH and the extent to which it differs from the primate have been under-appreciated within previous 2D studies. Properly understood, these anatomic differences may provide new insights into the relative susceptibilities of the rat and primate ONH to elevated intraocular pressure.

Diagnostic Accuracy of Spectralis SD OCT Automated Macular Layers Segmentation to Discriminate Normal from Early Glaucomatous Eyes

PURPOSEnTo evaluate the accuracy of the macular retinal layer segmentation software of the Spectralis spectral-domain (SD) optical coherence tomography (OCT) device (Heidelberg Engineering, Inc., Heidelberg, Germany) to discriminate between healthy and early glaucoma (EG) eyes.nnnDESIGNnProspective, cross-sectional study.nnnPARTICIPANTSnForty EG eyes and 40 healthy controls were included.nnnMETHODSnAll participants were examined using the standard posterior pole and the peripapillary retinal nerve fiber layer (pRNFL) protocols of the Spectralis OCT device. Using an Early Treatment Diagnostic Retinopathy Study circle at the macular level, the automated retinal segmentation software was applied to determine thicknesses of the following parameters: total retinal thickness, inner retinal layer (IRL), macular retinal nerve fiber layer (mRNFL), macular ganglion cell layer (mGCL), macular inner plexiform layer (mIPL), macular inner nuclear layer (mINL), macular outer plexiform layer (mOPL), macular outer nuclear layer (mONL), photoreceptors (PR), and retinal pigmentary epithelium (RPE). The ganglion cell complex (GCC) was determined by adding the mRNFL, mGCL, and mIPL parameters and the ganglion cell layer-inner plexiform layer (mGCL-IPL) was determined by combining the mGCL and mIPL parameters. Thickness of each layer was compared between the groups, and the layer and sector with the best area under the receiver operating characteristic curve (AUC) were identified.nnnMAIN OUTCOME MEASURESnComparison of pRNFL, IRL, mRNFL, mGCL, mIPL, mGCC, mGCL-IPL, mINL, mOPL, mONL, PR, and RPE parameters and total retinal thicknesses between groups for the different areas and their corresponding AUCs.nnnRESULTSnPeripapillary RNFL was significantly thinner in the EG group globally and in all 6 sectors assessed (Pxa0< 0.0005). For the macular variables, retinal thickness was significantly reduced in the EG group for total retinal thickness, mIRL, mRNFL, mGCL, and mIPL. The 2 best isolated parameters to discriminate between the 2 groups were pRNFL (AUC, 0.956) and mRNFL (AUC, 0.906). When mRNFL, mGCL, and mIPL measurements were combined (mGCC and mGCL plus mIPL), then its diagnostic performance improved (AUC, 0.940 and 0.952, respectively).nnnCONCLUSIONSnMacular RNFL, mGCL-IPL, and mGCC measurements showed a high diagnostic capability to discriminate between healthy and EG participants. However, macular intraretinal measurements still have not overcome standard pRNFL parameters.

Expansions of the neurovascular scleral canal and contained optic nerve occur early in the hypertonic saline rat experimental glaucoma model

PURPOSEnTo characterize early optic nerve head (ONH) structural change in rat experimental glaucoma (EG).nnnMETHODSnUnilateral intraocular pressure (IOP) elevation was induced in Brown Norway rats by hypertonic saline injection into the episcleral veins and animals were sacrificed 4 weeks later by perfusion fixation. Optic nerve cross-sections were graded from 1 (normal) to 5 (extensive injury) by 5 masked observers. ONHs with peripapillary retina and sclera were embedded, serial sectioned, 3-D reconstructed, delineated, and quantified. Overall and animal-specific EG versus Control eye ONH parameter differences were assessed globally and regionally by linear mixed effect models with significance criteria adjusted for multiple comparisons.nnnRESULTSnExpansions of the optic nerve and surrounding anterior scleral canal opening achieved statistical significance overall (pxa0<xa00.0022), and in 7 of 8 EG eyes (pxa0<xa00.005). In at least 5 EG eyes, significant expansions (pxa0<xa00.005) in Bruchs membrane opening (BMO) (range 3-10%), the anterior and posterior scleral canal openings (8-21% and 5-21%, respectively), and the optic nerve at the anterior and posterior scleral canal openings (11-30% and 8-41%, respectively) were detected. Optic nerve expansion was greatest within the superior and inferior quadrants. Optic nerve expansion at the posterior scleral canal opening was significantly correlated to optic nerve damage (Rxa0=xa00.768, p =xa00.042).nnnCONCLUSIONnIn the rat ONH, the optic nerve and surrounding BMO and neurovascular scleral canal expand early in their response to chronic experimental IOP elevation. These findings provide phenotypic landmarks and imaging targets for detecting the development of experimental glaucomatous optic neuropathy in the rat eye.

Glaucoma progression detection: agreement, sensitivity, and specificity of expert visual field evaluation, event analysis, and trend analysis.

Purpose. To assess sensitivity, specificity, and agreement among automated event analysis, automated trend analysis, and expert evaluation to detect glaucoma progression. Methods. This was a prospective study that included 37 eyes with a follow-up of 36 months. All had glaucomatous disks and fields and performed reliable visual fields every 6 months. Each series of fields was assessed with 3 different methods: subjective assessment by 2 independent teams of glaucoma experts, glaucoma/guided progression analysis (GPA) event analysis, and GPA (visual field index-based) trend analysis. Kappa agreement coefficient between methods and sensitivity and specificity for each method using expert opinion as gold standard were calculated. Results. The incidence of glaucoma progression was 16% to 18% in 3 years but only 3 cases showed progression with all 3 methods. Kappa agreement coefficient was high (k=0.82) between subjective expert assessment and GPA event analysis, and only moderate between these two and GPA trend analysis (k=0.57). Sensitivity and specificity for GPA event and GPA trend analysis were 71% and 96%, and 57% and 93%, respectively. Conclusions. The 3 methods detected similar numbers of progressing cases. The GPA event analysis and expert subjective assessment showed high agreement between them and moderate agreement with GPA trend analysis. In a period of 3 years, both methods of GPA analysis offered high specificity, event analysis showed 83% sensitivity, and trend analysis had a 66% sensitivity.

Diagnostic accuracy of imaging devices in glaucoma: A meta-analysis

Imaging devices such as the Heidelberg retinal tomograph-3 (HRT3), scanning laser polarimetry (GDx), and optical coherence tomography (OCT) play an important role in glaucoma diagnosis. A systematic search for evidence-based data was performed for prospective studies evaluating the diagnostic accuracy of HRT3, GDx, and OCT. The diagnostic odds ratio (DOR) was calculated. To compare the accuracy among instruments and parameters, a meta-analysis considering the hierarchical summary receiver-operating characteristic model was performed. The risk of bias was assessed using quality assessment of diagnostic accuracy studies, version 2. Studies in the context of screening programs were used for qualitative analysis. Eighty-six articles were included. The DOR values were 29.5 for OCT, 18.6 for GDx, and 13.9 for HRT. The heterogeneity analysis demonstrated statistically a significant influence of degree of damage and ethnicity. Studies analyzing patients with earlier glaucoma showed poorer results. The risk of bias was high for patient selection. Screening studies showed lower sensitivity values and similar specificity values when compared with those included in the meta-analysis. The classification capabilities of GDx, HRT, and OCT were high and similar across the 3 instruments. The highest estimated DOR was obtained with OCT. Diagnostic accuracy could be overestimated in studies including prediagnosed groups of subjects.

Sectioning a luxated intraocular lens inside the vitreous cavity

UNLABELLEDnWe describe a new technique for sectioning an intraocular lens (IOL) inside the vitreous cavity. The IOL had a broken haptic and was accidentally luxated after a complicated cataract surgery with posterior capsule rupture. The primary indication to cut the IOL in half inside the vitreous cavity is to preserve the anterior capsule integrity, especially in a small-sized capsulotomy, allowing subsequent implantation of a new IOL in the sulcus with the optical zone captured in the capsulorhexis.nnnFINANCIAL DISCLOSUREnNeither author has a financial or proprietary interest in any material or method mentioned.

A methodology for individual-specific modeling of rat optic nerve head biomechanics in glaucoma

Glaucoma is the leading cause of irreversible blindness and involves the death of retinal ganglion cells (RGCs). Although biomechanics likely contributes to axonal injury within the optic nerve head (ONH), leading to RGC death, the pathways by which this occurs are not well understood. While rat models of glaucoma are well-suited for mechanistic studies, the anatomy of the rat ONH is different from the human, and the resulting differences in biomechanics have not been characterized. The aim of this study is to describe a methodology for building individual-specific finite element (FE) models of rat ONHs. This method was used to build three rat ONH FE models and compute the biomechanical environment within these ONHs. Initial results show that rat ONH strains are larger and more asymmetric than those seen in human ONH modeling studies. This method provides a framework for building additional models of normotensive and glaucomatous rat ONHs. Comparing model strain patterns with patterns of cellular response seen in studies using rat glaucoma models will help us to learn more about the link between biomechanics and glaucomatous cell death, which in turn may drive the development of novel therapies for glaucoma.

Bleb revision for resolution of hypotony maculopathy following primary trabeculectomy.

1. Ostheimer TA, Burkholder BM, Leung TG, Butler NJ,Dunn JP, Thorne JE. Tattoo-associated uveitis. Am J Ophthal-mol 2014;158(3):637–643.2. Mansour AM, Chan CC. Recurrent uveitis preceded byswelling of skin tattoos. Am J Ophthalmol 1991;111(4):515–516.3. KlugerN.Sarcoidosisontattoos:areviewoftheliteraturefrom1939 to 2011. Sarcoidosis Vasc Diffuse Lung Dis 2013;30(2):86–102.4. BhuvaAN,LotaHK.A34yearoldmanwithbilateralanterioruveitis and a rash. BMJ 2011;343:d6831.5. Hanada K, Chiyoya S, Katabira Y. Systemic sarcoidal reactionin tattoo. Clin Exp Dermatol 1985;10(5):479–484.6. Jacob J, Van Calster J. Skin tattoos and the development ofuveitis. Acta Ophthalmol 2013;91(8):650–652.