Examination: A, Two pearls (50 and 10 μm) at base of dentate processes. B, Detail shows pearl partially covered by retinal pigment epithelium. Photomicrographs: C, Calcified pearl (fractured during microtomy) (hematoxylin-eosin). D, Pearl without attachment to the Bruch membrane, still partially covered by retinal pigment epitheliumand retinal tuft (hematoxylin-eosin ×400).
Scanning electron microscopy (backscattered electron image) of pearl at low power (A) and high power (B). C, X-ray spectrum shows peaks for calcium and phosphorus, consistent with calcium phosphate.
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Wright L, Eagle RE, Abraham JL, Barker-Griffith AE. Elemental Composition of Ora Serrata Pearls—A Form of Focal Nodular Drusen. JAMA Ophthalmol. 2016;134(5):601–603. doi:10.1001/jamaophthalmol.2016.0327
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 structures have not been described, although there is suggestion that they consist of drusenlike material. In this study, scanning electron microscopy with energy dispersive x-ray spectroscopy (SEM-EDS) was applied in conjunction with classic histochemical staining techniques to characterize the elemental content of these pearls.
A formalin-fixed enucleated globe was submitted for routine pathological examination and found to contain 3 pearls at the region of the ora serrata. Sections of the gross specimen 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. Specimens were embedded in paraffin and submitted for hematoxylin-eosin, periodic acid–Schiff, and van Gieson elastic stains. A section was placed on a carbon stub for SEM-EDS using the FEI Aspex personal scanning electron microscope (FEI Inc).
On gross examination, 3 pearls were located at the dentate 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 discrete heterogeneous masses that demonstrated emission peaks corresponding to calcium and phosphorus, suggesting the presence of calcium phosphate.
Ora serrata pearls have been described in the literature as idiopathic drusenlike material based on their general appearance and simple staining patterns. In this study, we described the histopathological appearance (Figure 1) and elemental composition of ora serrata pearls. As in past studies, pearls were observed by light microscopy as eosinophilic periodic acid–Schiff–positive spheres located within or beneath retinal tissue, projecting from the Bruch membrane and covered by retinal pigment epithelium.1 Using SEM-EDS, we have demonstrated that the calcium within ora serrata pearls is in the form of calcium phosphate (Figure 2), the same calcium salt seen in dystrophic calcification of drusen.2 We found ora serrata pearls to be morphologically consistent with focal nodular drusen, indistinguishable from drusen previously described.3
The presence of drusen in any form in the furthest extent of the peripheral retina may help explain the pathophysiologic mechanism of its formation. We found ora serrata pearls only in elongations of dentate processes, which lie anterior to the termination of the choriocapillaris in an area made up mostly of veins.4 The propensity of pearls to form in this low-oxygen tension area, and not in areas of richer oxygen supply, such as the oral bays, is well documented.1,5,6 This pattern of formation suggests a pathophysiologic mechanism involving ischemia-induced retinal degeneration. In light of our SEM-EDS analyses that characterize pearls as calcified drusen, we may infer that a similar ischemic process underlies the formation of other retinal drusen. Because ischemia is a known trigger for phosphate-dependent calcium accumulation (eg, in mitochondria), the paucity of arterioles at dentate processes would similarly explain the extensive calcification that can be seen in pearls of the ora serrata.
In conclusion, we propose that pearls are not idiopathic developmental bodies, but rather drusen that result from physiologic, age-related, or other ischemic change. While pearls do not affect vision, they remain clinically relevant because their composition and distribution may support an ischemic basis for the development of drusen-related disease.
Corresponding Author: Ann E. Barker-Griffith, MD, FRCSC, State University of New York Upstate Medical University, 766 Irving Ave, Room 2137-WH, Syracuse, NY 13210 (email@example.com).
Published Online: March 24, 2016. doi:10.1001/jamaophthalmol.2016.0327.
Author Contributions: Drs Barker-Griffith and Abraham had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Abraham, Barker-Griffith.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Wright, Abraham, Barker-Griffith.
Critical revision of the manuscript for important intellectual content: Eagle, Abraham, Barker-Griffith.
Administrative, technical, or material support: Barker-Griffith, Abraham.
Study supervision: Abraham.
Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Barker-Griffith 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 York, Upstate Medical University. Allergan had no role in the funding of this project. No other conflicts were reported.
Funding/Support: This study was supported by unrestricted grants from Research to Prevent Blindness Inc; Lions District 20-Y1 of Central New York, Syracuse; and Empire State Development–Division of Science, Technology and Innovation.
Role of the Funder/Sponsor: The funding sources had no role in the design and conduct of this study; collection, management, analysis, and interpretation of the data preparation; review or approval of the manuscript; and decision to submit the manuscript for publication.
Additional Contributions: We thank Henry D. Friedman, MD, State Univeristy of New York Upstate Medical University, for graciously offering time and expertise in pathology and German translation. He was not compensated for this work.
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