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

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. Letters to the Editor FIG. 2. A. Enhanced depth imaging optical coherence tomography (EDI-OCT) of a healthy 12-year-old boy with a congenitally small optic disc with slight blurring of the disc margin nasally and peripapillary hyperreflective ovoid mass-like structure (PHOMS) (red arrow) corresponding to the area of disc blurring. B. Follow-up EDI-OCT of the same boy acquired 5 years later. The PHOMS (red arrow) has not evolved into ODD but has slightly regressed over the years corresponding to a diminished appearance of pseudopapilledema. 6) We have evidence that PHOMS regress in patients with IIH after intracranial pressure (ICP) lowering therapy (unpublished data). The concept of PHOMS as herniating nerve fibers above the Bruch membrane layer is supported by Wang et al (6) in a recently published study. We agree with Lee et al that PHOMS have only been possible to visualize because of emerging OCT techniques, but as PHOMS are located close to the inner limiting membrane, the use of enhanced depth imaging is not a requirement. Furthermore, we agree with Lee et al that PHOMS should be regarded as a different entity. We believe it is a nonspecific marker of distended or displaced axons, axoplasmic stasis, or congestion in the prelaminar optic nerve head. In patients with papilledema, axoplasmic stasis is most likely caused by increased retrolaminar tissue pressure induced by high ICP. In ODD patients with pseudopapilledema, PHOMS is most likely caused by local congestion, possibly due to a primary axonopathy or mass effect compressing neighboring axons, although the specific pathophysiology is still not understood. When it comes to the diagnosis of ODD using OCT, we do not agree with Lee et al that we need to restrict our definition of ODD to include only calcified masses within the optic nerve head. In our study, we also included buried ODD. These ODD were situated deep in the optic nerve head and were hyporeflective, with minimal or no hyperreflective margin. In 5-year follow-up of enhanced depth Letters to the Editor: J Neuro-Ophthalmol 2018; 38: 566-574 imaging OCT scans from a previously published study of children with ODD (10), we saw that hyporeflective areas in the deep layer of the optic nerve head (what we define as buried ODD) evolved into larger and slightly more calcified ODD (Fig. 1). However, when looking through the followup data, we never saw PHOMS evolve into ODD (Fig. 2). Could PHOMS be an early form of ODD or turn into ODD as speculated by Lee et al and previously by Traber et al (4)? We, too, have seen ODD located inside PHOMS. ODD can be found everywhere among the axonal tissue of the prelaminar optic nerve head, and there is no reason not to expect them within the nerve fibers of PHOMS as well. We believe that there is currently no evidence to support the theory that PHOMS are early ODD or might evolve into ODD. As we argue above, PHOMS should not be seen as a differential diagnosis of optic disc edema but rather as a manifestation of the edema. PHOMS do not always correlate with the degree of papilledema or pseudopapilledema, and sometimes, we see PHOMS in individuals with healthy eyes (Fig. 2). Most likely, congenital optic disc anatomy and other factors play a role in the development and degree of PHOMS, rather than being an independent disease process. By recognizing PHOMS as a marker of axoplasmic stasis, we might be able to use PHOMS in the diagnostics and disease tracking of different optic neuropathies. Only future studies will tell us the possible impact of this finding, meanwhile we would caution against confusing PHOMS with early or buried ODD, although they may sometimes coexist. 569 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Letters to the Editor Lasse Malmqvist, MD Department of Ophthalmology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark Judith Warner, MD John A. Moran Eye Centre, University of Utah, Salt Lake City, Utah Lulu Bursztyn, MSc, MD Department of Ophthalmology, Western University, London, Canada Marianne Wegener, MD Department of Ophthalmology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark Fiona Costello, MD, PhD Departments of Clinical Neurosciences and Surgery, University of Calgary, Calgary, Canada Sui Wong, MD Moorfields Eye Hospital, London, United Kingdom Neuro-ophthalmology Expertise Centre, VUmc, Amsterdam, Netherlands Kathleen Digre, MD John A. Moran Eye Centre, University of Utah, Salt Lake City, Utah J. Alexander Fraser, MD Department of Ophthalmology, Western University, London, Canada Department of Clinical Neurological Sciences, Western University, London, Canada Clare Fraser, MMed Save Sight Institute, University of Sydney, Sydney, Australia Bradley Katz, MD, PhD John A. Moran Eye Centre, University of Utah, Salt Lake City, Utah Mitchell Lawlor, FRANZCO, PhD Sydney Eye Hospital, Sydney, Australia Axel Petzold, MD, PhD Moorfields Eye Hospital, London, United Kingdom Neuro-ophthalmology Expertise Centre, VUmc, Amsterdam, Netherlands Patrick Sibony, MD Department of Ophthalmology, State University of New York at Stony Brook, Stony Brook, New York 570 Steffen Hamann, MD, PhD Department of Ophthalmology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark The authors report no conflicts of interest. 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 ahead of print October 24, 2017] doi: 10.1097/ WNO.0000000000000585. 2. 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. 3. 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.e1. 4. 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. 5. Bassi ST, Mohana KP. Optical coherence tomography in papilledema and pseudopapilledema with and without optic nerve head drusen. Indian J Ophthalmol. 2014;62:1146-1151. 6. Wang DD, Leong JCY, Gale J, Wells AP. Multimodal imaging of buried optic nerve head drusen. Eye (Lond). [published online ahead of print January 30, 2018] doi: 10.1038/s41433-0170009-8. 7. Paton L, Holmes G. The pathology of papilledema: a historical study of sixty eyes. Brain. 1911;33:389-432. 8. Tso MO. Pathology and pathogenesis of drusen of the optic nerve head. Ophthalmology. 1981;88:1066-1080. 9. Malmqvist L, Fraser C, Fraser JA, Lawlor M, Hamann S. RE: Traber et al: enhanced depth imaging optical coherence tomography of optic nerve head drusen: a comparison of cases with and without visual field loss. Ophthalmology. 2017;124:e55-e56. 10. Malmqvist L, Li XQ, Eckmann CL, Skovgaard AM, Olsen EM, Larsen M, Munch IC, Hamann S. Optic disc drusen in children: the Copenhagen Child Cohort 2000 eye study. J Neuroophthalmol. 2018;38:140-146. Letters to the Editor: J Neuro-Ophthalmol 2018; 38: 566-574 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.