Peripapillary Hyperreflective Ovoid Mass-Like Structures: Is It Optic Disc Drusen or Not?

Letters to the Editor Peripapillary Hyperreflective Ovoid Mass-Like Structures: Is It Optic Disc Drusen or Not? W e read with great interest the recent recommendations for diagnosing optic disc drusen (ODD) put forth by Malmqvist et al (1). As suggested by the authors, we agree that establishing guidelines for the diagnosis of ODD using spectral domain optical coherence tomography (SD-OCT) through the enhanced depth imaging (EDI) technique is very important. The suggested Optic Disc Drusen Studies (ODDS) Consortium diagnostic recommendations posit that ODD always have a hyporeflective core, and that the peripapillary hyperreflective ovoid mass-like structure (PHOMS), which are often regarded as buried ODD, should not be diagnosed as ODD. Although we mostly agree with the consensus of the consortium, we would like to raise the following question: If PHOMS is not diagnosed as ODD, then what does it represent? ODD with signal-poor cores on B-scan SD-OCT images are often visible on funduscopy (2,3). We thought they would show high attenuation with acoustic shadowing on B-scan ultrasonography and show a fundus autofluorescence given that these findings are likely related to calcification (4). We believe it would be more appropriate if the consortium decides to restrict the meaning of ODD to only include the calcified mass within the optic nerve head. Then, how could pseudopapilledema be explained? As the authors have stated, ODD were always detected above the lamina cribrosa. Considering the transparency of the retina, the nonvisualization of the signals in patients with pseudopapilledema could be understood in two ways. First, ODD could be buried deep (beneath the lamina cribrosa) obscuring full visualization. Second, it could be that ODD have insufficient signals for detection. In the former case, it is highly unlikely that large ODD can pass through the small pores of the lamina cribrosa. Therefore, most of the pseudopapilledema cases in the past should have been classified as PHOMS, acellular deposits without enough signals of calcification. Hence, if we were to exclude PHOMS from ODD, it becomes difficult diagnosing such cases that are not either normal or ODD. At this point, we want to stress that PHOMS should be regarded as a separate diagnostic entity if the current definition of ODD, based on EDI SD-OCT, is adopted. In addition, it should be noted that PHOMS is more important clinically than ODD since the differentiation of PHOMS from optic disc edema is more difficult than that of ODD. Although, the authors did not mention it as a limitation of their report, only patients 18 years and older were studied. Because presumed PHOMS cases (pseudopapilledema or buried ODD) would be more frequent in young subjects (2,5,6), this inclusion criteria might lead to selection bias: ODD with signal- Letters to the Editor: J Neuro-Ophthalmol 2018; 38: 566-574 poor cores in elderly people would have been selectively included. Recently, Traber et al (3) reported that PHOMS on SD-OCT images corresponded to the granulation tissue in the histologic section of ODD. This granulation tissue also was observed around the calcium flecks of ODD in a histologic study (4). Therefore, PHOMS may form during evolution to ODD. If PHOMS are herniated nerve fibers as the authors speculated, then a connection between the PHOMS and axons should be present. This would require neuronal marker staining or electron microscopic evidence because PHOMS may consist of non-neural glial cells mixed with extracellular matrix. We believe that the previous histologic study results favor a mixture of various cells and extracellular material over the herniated nerve fibers as the origin of PHOMS (4,7). The relationship between PHOMS and ODD remains unclear. We speculate that PHOMS could turn into ODD through cystic degeneration (hyporeflectance core) and calcification (hyperreflectance dots) in elderly patients. Our reasoning is two-fold. First, in all cases of ODD, PHOMS existed around ODD. In other words, ODD appeared within PHOMS (2,8). Second, we previously reported a case of PHOMS having a fundus autofluorescence (9), although the ODDS consortium asserted that PHOMS do not autofluoresce (1). Our case may represent a transition status between PHOMS and ODD. Proof of this would require a long-term, longitudinal study. In conclusion, we assert that if ODD are defined according to the current guidelines, then PHOMS should be regarded as a different diagnostic entity. Many alleged cases of buried ODD and pseudopapilledema may belong to this entity. PHOMS should be evaluated with great caution and it may be that PHOMS is a transitional structure leading to formation of ODD (9). Kyoung Min Lee, MD Department of Ophthalmology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea Se Joon Woo, MD, PhD Department of Ophthalmology, Seoul National University Bundang Hospital, Seongnam, Korea Jeong-Min Hwang, MD, PhD Department of Ophthalmology, Seoul National University Bundang Hospital, Seongnam, Korea The authors report no conflicts of interest. 567 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Letters to the Editor REFERENCES 1. Malmqvist L, Bursztyn L, Costello F, Digre K, Fraser JA, Fraser C, Katz B, Lawlor M, Petzold A, Sibony P, Warner J, Wegener M, Wong S, Hamann S. The Optic Disc Drusen Studies Consortium recommendations for diagnosis of optic disc drusen using optical coherence tomography. J Neuroophthalmol. [published online ahead of print October 24, 2017] doi: 10.1097/ WNO.0000000000000585. 2. Lee KM, Woo SJ, Hwang JM. Morphologic characteristics of optic nerve head drusen on spectral-domain optical coherence tomography. Am J Ophthalmol. 2013;155:1139-1147. 3. Traber GL, Weber KP, Sabah M, Keane PA, Plant GT. Enhanced depth imaging optical coherence tomography of optic nerve head drusen: a comparison of cases with and without visual field loss. Ophthalmology. 2017;124:66-73. Peripapillary Hyperreflective Ovoid MassLike Structures: Is It Optic Disc Drusen or Not?: Response W e thank Lee et al for their letter regarding our recently published recommendations regarding the diagnosis of optic disc drusen (ODD) (1) because they raise several important questions. The main purpose of our study was to establish welldefined recommendations for the diagnosis of ODD using optical coherence tomography (OCT). During this process, we came across the peripapillary hyperreflective mass-like structures (PHOMS). Several studies previously have diagnosed PHOMS as buried ODD (2- 5). We argue that PHOMS are not ODD but are in fact 4. Tso MO. Pathology and pathogenesis of drusen of the optic nerve head. Ophthalmology. 1981;88:1066-1080. 5. Lee KM, Woo SJ, Hwang JM. Differentiation of optic nerve head drusen and optic disc edema with spectral-domain optical coherence tomography. Ophthalmology. 2011;118:971-977. 6. Chang MY, Pineles SL. Drusen of the optic disc. A retrospective study in cadaver eyes. Surv Ophthalmol. 2016;61:745-758. 7. Friedman AH, Gartner S, Modi SS. Drusen of the optic disc. A retrospective study in cadaver eyes. Br J Ophthalmol. 1975;59:413-421. 8. Sato T, Mrejen S, Spaide RF. Multimodal imaging of optic disc drusen. Am J Ophthalmol. 2013;156:275-282.e271. 9. Lee KM, Woo SJ, Hwang JM. Fundus autofluorescence in the buried optic disc drusen: optical coherence tomography findings. Can J Ophthalmol. 2017;52:e52-e53. herniating nerve observations: fibers based on the following 1) The morphology of PHOMS on OCT differs from ODD that has been verified by fundus photography or autofluorescence (6). 2) Histopathology from eyes with papilledema stains positive for nerve fibers in areas corresponding to PHOMS (7). 3) Histopathology of PHOMS from eyes with ODD is indistinguishable from PHOMS seen in eyes with papilledema (8). 4) PHOMS are always located in the peripapillary circumference, corresponding to the area of optic disc margin blurring in patients with papilledema or pseudopapilledema (1). 5) PHOMS are found in a variety of conditions with optic disc swelling such as idiopathic intracranial hypertension (IIH) (9). FIG. 1. A. Enhanced depth imaging optical coherence tomography (EDI-OCT) of a 12-year-old girl with buried optic disc drusen (ODD) (red arrow). B. Follow-up EDI-OCT of the same girl acquired 5 years later. The buried ODD (red arrow) has become larger and exhibits a more calcified margin. 568 Letters to the Editor: J Neuro-Ophthalmol 2018; 38: 566-574 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.