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Elemental Composition of Ora Serrata Pearls—A Form of Focal Nodular

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Elemental Composition of Ora Serrata Pearls—A Form of Focal Nodular Letters RESEARCH LETTER Figure 1. Ora Serrata Pearls Elemental Composition of Ora Serrata Pearls— A Two pearls (50 and 10 µm) B Detailed image A Form of Focal Nodular Drusen Examination of the peripheral fundus may reveal discrete pearl- like structures at the furthest extent of the retina. They occur throughout the ora serrata region, but only where a tongue of retina tissue in the form of a dentate process overlies the pars plana. In the later stages, the pigment epithelial covering is lost, exposing the pearl as a glistening bead. To our knowledge, the clinical significance and precise composition of these struc- tures have not been described, although there is suggestion that they consist of drusenlike material. In this study, scan- ning electron microscopy with energy dispersive x-ray spec- troscopy (SEM-EDS) was applied in conjunction with classic histochemical staining techniques to characterize the elemen- tal content of these pearls. Methods | A formalin-fixed enucleated globe was submitted for routine pathological examination and found to contain 3 pearls C Calcified pearl D Pearl without attachment to the at the region of the ora serrata. Sections of the gross speci- Bruch membrane men were photographed, dissected (R.E.E.), and sent to the Barbara W. Streeten Ocular Pathology Laboratory at the State University of New York Upstate Medical University. Speci- mens were embedded in paraffin and submitted for hema- toxylin-eosin, periodic acid–Schiff, and van Gieson elastic 200 µm stains. A section was placed on a carbon stub for SEM-EDS using the FEI Aspex personal scanning electron microscope (FEI Inc). Results | On gross examination, 3 pearls were located at the den- tate processes of the ora serrata. Light microscopy revealed that the pearls were attached to the Bruch membrane and covered by retinal pigment epithelium cells and neurosensory retina. The pearl-like masses stained positively with periodic acid–Schiff and stained negatively with van Gieson elastic. Scanning electron microscopy with energy dispersive x-ray spectroscopy showed Examination: A, Two pearls (50 and 10 μm) at base of dentate processes. discrete heterogeneous masses that demonstrated emission B, Detail shows pearl partially covered by retinal pigment epithelium. peaks corresponding to calcium and phosphorus, suggesting the Photomicrographs: C, Calcified pearl (fractured during microtomy) presence of calcium phosphate. (hematoxylin-eosin). D, Pearl without attachment to the Bruch membrane, still partially covered by retinal pigment epitheliumand retinal tuft (hematoxylin-eosin ×400). Discussion | Ora serrata pearls have been described in the litera- ture as idiopathic drusenlike material based on their general ap- pearance and simple staining patterns. In this study, we de- to be morphologically consistent with focal nodular drusen, in- scribed the histopathological appearance (Figure 1) and distinguishable from drusen previously described.3 elemental composition of ora serrata pearls. As in past studies, The presence of drusen in any form in the furthest extent pearls were observed by light microscopy as eosinophilic peri- of the peripheral retina may help explain the pathophysi- odic acid–Schiff–positive spheres located within or beneath reti- ologic mechanism of its formation. We found ora serrata pearls nal tissue, projecting from the Bruch membrane and covered only in elongations of dentate processes, which lie anterior to by retinal pigment epithelium.1 Using SEM-EDS, we have dem- the termination of the choriocapillaris in an area made up onstrated that the calcium within ora serrata pearls is in the form mostly of veins.4 The propensity of pearls to form in this low- of calcium phosphate (Figure 2), the same calcium salt seen in oxygen tension area, and not in areas of richer oxygen supply, dystrophic calcification of drusen.2 We found ora serrata pearls such as the oral bays, is well documented.1,5,6 This pattern jamaophthalmology.com (Reprinted) JAMA Ophthalmology May 2016 Volume 134, Number 5 601 Copyright 2016 American Medical Association. All rights reserved. Downloaded From: http://jamanetwork.com/ by Sociedad Mexicana de Oftalmologia on 08/10/2017 Letters Figure 2. Scanning Electron Microscopy–Energy Dispersive X-ray Spectroscopy of an Ora Serrata Pearl A Low power B High power 270 µm 80.0 µm C X-ray spectrum Dead Time = 1.2% 561 Ca Live Time = 9.0 Real Time = 9.1 CPS = 1814 421 P Scanning electron microscopy 280 (backscattered electron image) of 140 C pearl at low power (A) and high SK NaMg Fe power (B). C, X-ray spectrum shows 0 0.00 1.28 2.56 3.84 5.12 6.40 7.68 8.96 10.24 peaks for calcium and phosphorus, consistent with calcium phosphate. of formation suggests a pathophysiologic mechanism in- Published Online: March 24, 2016. doi:10.1001/jamaophthalmol.2016.0327. volving ischemia-induced retinal degeneration. In light of Author Contributions: Drs Barker-Griffith and Abraham had full access to all of our SEM-EDS analyses that characterize pearls as calcified dru- the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. sen, we may infer that a similar ischemic process underlies the Study concept and design: Abraham, Barker-Griffith. formation of other retinal drusen. Because ischemia is a known Acquisition, analysis, or interpretation of data: All authors. trigger for phosphate-dependent calcium accumulation (eg, in Drafting of the manuscript: Wright, Abraham, Barker-Griffith. mitochondria), the paucity of arterioles at dentate processes Critical revision of the manuscript for important intellectual content: Eagle, Abraham, Barker-Griffith. would similarly explain the extensive calcification that can be Administrative, technical, or material support: Barker-Griffith, Abraham. seen in pearls of the ora serrata. Study supervision: Abraham. In conclusion, we propose that pearls are not idiopathic Conflict of Interest Disclosures: All authors have completed and submitted the developmental bodies, but rather drusen that result from physi- ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Barker-Griffith ologic, age-related, or other ischemic change. While pearls do received grant 1121175-69695-1 from Allergan Sales Inc for a different research project administered by the Research Foundation of the State University of New not affect vision, they remain clinically relevant because their York, Upstate Medical University. Allergan had no role in the funding of this composition and distribution may support an ischemic basis project. No other conflicts were reported. for the development of drusen-related disease. Funding/Support: This study was supported by unrestricted grants from Research to Prevent Blindness Inc; Lions District 20-Y1 of Central New York, Lauren Wright, MD Syracuse; and Empire State Development–Division of Science, Technology and Innovation. Ralph E. Eagle Jr, MD Role of the Funder/Sponsor: The funding sources had no role in the design and Jerrold L. Abraham, MD conduct of this study; collection, management, analysis, and interpretation of Ann E. Barker-Griffith, MD, FRCSC the data preparation; review or approval of the manuscript; and decision to submit the manuscript for publication. Author Affiliations: Department of Ophthalmology, State University of New Additional Contributions: We thank Henry D. Friedman, MD, State Univeristy York Upstate Medical University, Syracuse (Wright, Barker-Griffith); Department of New York Upstate Medical University, for graciously offering time and of Ophthalmology, University of Texas Health Science Center at San Antonio expertise in pathology and German translation. He was not compensated for (Wright); Wills Eye Hospital, Thomas Jefferson University, Philadelphia, this work. Pennsylvania (Eagle); Department of Pathology, State University of New York Upstate Medical University, Syracuse (Abraham, Barker-Griffith). 1. Lonn LI, Smith TR. Ora serrata pearls: clinical and histological correlation. Arch Ophthalmol. 1967;77(6):809-813. Corresponding Author: Ann E. Barker-Griffith, MD, FRCSC, State University of New York Upstate Medical University, 766 Irving Ave, Room 2137-WH, Syracuse, 2. Ulshafer RJ, Allen CB, Nicolaissen B Jr, Rubin ML. Scanning electron NY 13210 ([email protected]). microscopy of human drusen. Invest Ophthalmol Vis Sci. 1987;28(4):683-689. 602 JAMA Ophthalmology May 2016 Volume 134, Number 5 (Reprinted) jamaophthalmology.com Copyright 2016 American Medical Association. All rights reserved. Downloaded From: http://jamanetwork.com/ by Sociedad Mexicana de Oftalmologia on 08/10/2017 Letters 3. Kapur R, Pulido JS, Abraham JL, Sharma M, Buerk B, Edward DP. Histologic findings after surgical excision of optic nerve head drusen. Retina. 2008;28(1): Figure 1. Postmortem Eye Finding in a Patient With Ocular Exposure 143-146. 4. Fryczkowski A. Blood vessels of the eye and their changes in diabetes. In: Motta P, Murakami T, Fujita H, eds. Scanning Electron Microscopy Of Vascular Casts: Methods and Applications. New York, NY: Springer; 1992:293-311. 5. Daicker B, Eisner G. The drusen of the ora serrata; their clinical aspects and pathalogic anatomy. Albrecht Von Graefes Arch Klin Exp Ophthalmol. 1968;174 (4):336-343. 6. Barker-Griffith AE, Streeten BW, Fikhman M, Gutman J. The ciliary body. In: Tasman W and Jaeger EA, eds. Duane's Ophthalmology, 2011 Edition. [DVD-ROM]. Philadelphia, PA: Lippincott Williams & Wilkins; 2011. OBSERVATION A Postmortem Ocular Finding of Tache Noire in a Living Patient Patients
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