Diagnostic dilemma of papilledema and pseudopapilledema.

BACKGROUND: Papilledema is the optic disc swelling caused by increased intracranial pressure (ICP) that can damage the optic nerve and cause subsequent vision loss. Pseudopapilledema refers to optic disc elevation without peripapillary fluid that can arise from several optic disc disorders, with optic disc drusen (ODD) being the most frequent cause. Occasionally, pseudopapilledema patients are mistakenly diagnosed as papilledema, leading to the possibility of unneeded procedures. We aim to thoroughly examine the most current evidence on papilledema and pseudopapilledema causes and several methods for distinguishing between both conditions. METHODS: An extensive literature search was conducted on electronic databases including PubMed and google scholar using keywords that were relevant to the assessed pathologies. Data were collected and then summarized in comprehensive form. RESULTS: Various techniques are employed to distinguish between papilledema and pseudopapilledema. These techniques include Fundus fluorescein angiography, optical coherence tomography, ultrasonography, and magnetic resonance imaging. Lumbar puncture and other invasive procedures may be needed if results are suspicious. CONCLUSION: Papilledema is a sight-threatening condition that may lead to visual affection. Many disc conditions may mimic papilledema. Accordingly, differentiation between papilledema and pseudopailledema is crucial and can be conducted through many modalities.

Concomitant optic disk drusen and papilledema due to idiopathic intracranial hypertension in a pediatric cohort.

BACKGROUND: Optic disk drusen (ODD) in pediatric patients typically presents with pseudopapilledema. Diagnosing concomitant papilledema due to idiopathic intracranial hypertension (IIH) in these patients can be challenging. The purpose of this study was to evaluate the incidence and clinical features of papilledema due to IIH among pediatric patients with a new diagnosis of ODD and to discuss the clinical and paraclinical findings that helped diagnose this group. METHODS: The medical records of children <15 years of age with ODD confirmed by B-scan ultrasound at their first visit over a 4-year period (2019-2022) were reviewed retrospectively. Patients with concurrent IIH were identified, and the demographic and clinical characteristics were reviewed. RESULTS: A total of 83 children with confirmed ODD at the initial presentation were included, of whom 4 (4.8%) were diagnosed with concomitant IIH. Patients ranged in age from 7 to 15 years; 3 of the 4 were female, and 3 had IIH-related symptoms at presentation (1 was asymptomatic). None of the 4 patients had papilledema greater than Frisen grade 2. CONCLUSIONS: We recommend that clinicians review pertinent IIH symptoms and risk factors in children with ODD and follow the standard workup for IIH in suspicious cases. In asymptomatic patients with a new diagnosis of ODD, we recommend obtaining a follow-up optic nerve evaluation and optical coherence tomography scan to detect any significant interval change that might serve as a possible indicator of concomitant papilledema.

The Presence of Optic Disc Drusen in Eyes with Uveitis.

PURPOSE: To evaluate the coexistence of optic disc drusen (ODD) in eyes with uveitis. METHODS: In this retrospective, observational study, patients followed up in a uvea clinic with all types of uveitis were evaluated. ODD were confirmed by ocular ultrasonography, optic nerve head enhanced-depth imaging optical coherence tomography, fundus autofluorescence, and fundus photography. RESULTS: ODD were detected in 17 of 545 (3.1%) uveitis patients. The mean age was 18.9 ± 10.4 years, and 76.5% were female. 45.5% were anterior, 42.4% were panuveitis, 6.1% were intermediate, and 6.1% were posterior uveitis. ODD were found bilaterally in all 17 patients; uveitis was unilateral in one patient. 58.8% were under the age of 18, and in this group, the rate of buried ODD was 78.9% (p = 0.039). In adults (seven patients), ODD were buried in 42.9%. CONCLUSION: ODD can be detected in eyes with uveitis and may clinically mimic optic disc edema, lead to misdiagnosis and/or overtreatment.

Influence of Patient Age and Presence of Optic Disc Drusen on Fluctuations in Retinal Nerve Fiber Layer Thickness.

BACKGROUND: It is generally believed that optic disc drusen (ODD) change only over long periods of time. Because, in our experience, this does not apply to younger patients, we investigated the natural course of changes of the peripapillary retinal nerve fiber layer (RNFL) in patients with ODD. METHODS: In this retrospective study, 40 eyes with and 40 eyes without ODD were examined, both cohorts were equally subdivided into younger subjects (20 years or younger) and older subjects (21 years or older). Three optical coherence tomography (OCT) scans of the peripapillary RNFL that had an interval of at least 1 month were required for each patient to be included in this study. The largest difference in total RNFL thickness (delta RNFL-t) and in RNFL thickness of the most differing sector (delta RNFL max) measured by OCT was compared. RESULTS: The differences in total RNFL thickness and in the most differing RNFL sector in the group of patients with ODD younger than 21 years were significantly larger than in each of the other 3 groups ( P = 0.0001). The other 3 groups did not differ significantly. CONCLUSIONS: Patients with ODD younger than 21 years have distinct variations in peripapillary RNFL thickness without evidence of increased intracranial pressure. In the absence of further pathological findings or neurological symptoms, an observational approach seems adequate in these patients.

Rates of Visual Field Change in Eyes With Optic Disc Drusen.

BACKGROUND: Optic disc drusen (ODD) are calcified deposits in the prelaminar portion of the optic nerve head. Although often asymptomatic, these deposits can cause progressive visual field defects and vision loss. The purpose of this study was to evaluate rates of functional loss in eyes with ODD and to investigate risk factors associated with rates of visual field progression. METHODS: This was a retrospective cohort study including 65 eyes of 43 patients with ODD from the Duke Ophthalmic Registry. All eyes had at least 12 months of follow-up and at least 3 reliable standard automated perimetry (SAP) tests. Linear mixed models were used to estimate rates of SAP mean deviation (MD) loss over time. Univariable and multivariable models were used to assess the effect of clinical variables and intraocular pressure (IOP) on rates of change. RESULTS: Subjects were followed for an average of 7.6 ± 5.3 years. The mean rate of SAP MD change was -0.23 ± 0.26 dB/year, ranging from -1.19 to 0.13 dB/year. Fifty-seven eyes (87.7%) had slow progression (slower than -0.5 dB/year), 6 eyes (9.2%) had moderate progression (between -0.5 dB/year and -1 dB/year), and 2 eyes (3.1%) had fast progression (faster than -1 dB/year). In multivariable models, older age and worse SAP MD at baseline were significantly associated with faster rates of change. Mean IOP was not associated with faster rates of MD change in both univariable and multivariable analyses. CONCLUSIONS: Most eyes with ODD had slow rates of visual field loss over time. Age and baseline severity were significantly associated with faster rates of visual field loss.

The visual morbidity of optic nerve head drusen: a longitudinal review.

BACKGROUND: The ophthalmologic complications of optic nerve head drusen (ONHD) in adults have been documented, whereas data on the degree of visual morbidity from OHND in children are limited. METHODS: The medical records of all patients diagnosed with ONHD at a single, tertiary care ophthalmology department from January 1, 2010, until July 1, 2018, were reviewed retrospectively. Patients were identified using ICD-9 and ICD-10 codes. Inclusion criteria were age ≤18 years of age and formal documentation of ONHD by ancillary testing. RESULTS: A total of 213 patients (386 eyes with ONHD) met inclusion criteria. Mean age at diagnosis was 10.13 ± 4.09 years, and mean follow-up was 2.76 ± 2.91 years. Formal visual fields were available for 208 eyes. Repeatable visual field defects were noted in 24 eyes (11.5%). The most common defect was a nasal step, which occurred in 11 eyes (45.8%). Fifteen eyes had visual field defects at presentation, and 9 eyes developed field loss within 1.39 ± 0.55 years of diagnosis. There was no correlation found between intraocular pressure and degree of visual field loss. Choroidal neovascular membranes were clinically apparent in 5 eyes and treatment was required in 3 eyes. Nonarteritic ischemic optic neuropathy developed in 2 eyes. CONCLUSIONS: Visual morbidity associated with ONHD in children is common and may develop in a short period of time after initial diagnosis. There was no correlation found with intraocular pressure.

Inner retinal degeneration associated with optic nerve head drusen in pseudoxanthoma elasticum.

BACKGROUND/AIMS: To determine the association of age, presence of optic nerve head drusen (ONHD) and number of previous intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections with inner retinal layer thicknesses in patients with pseudoxanthoma elasticum (PXE). METHODS: In this retrospective case-control study, longitudinal spectral-domain optical coherence tomography imaging data from patients with PXE were compared with controls. A custom deep-learning-based segmentation algorithm was trained and validated to quantify the retinal nerve fibre layer (RNFL) and ganglion cell layer (GCL). The association of age, number of anti-VEGF injections and ONHD with the RNFL and GCL thickness in the outer ETDRS subfields as dependent variables was investigated using mixed model regression. RESULTS: Fourty-eight eyes of 30 patients with PXE were compared with 100 healthy eyes. The mean age was 52.5±12.9 years (range 21.3-68.2) for patients and 54.2±18.7 years (range 18.0-84.5) for controls. In patients, ONHD were visible in 15 eyes from 13 patients and 31 eyes had received anti-VEGF injections. In the multivariable analysis, age (-0.10 µm/year, p<0.001), the diagnosis of PXE (-2.03 µm, p=0.005) and an interaction term between age and the presence of ONHD (-0.20 µm/year, p=0.001) were significantly associated with the GCL thickness. Including the number of intravitreal injections did not improve the model fit. The RNFL thickness was not significantly associated with any of these parameters. CONCLUSIONS: This study demonstrates a significant association of ageing and ONHD with GCL thinning in patients with PXE, but not with the number of anti-VEGF injections. Given the severity of inner retinal degeneration in PXE, a clinical trial investigating neuroprotective therapy warrants consideration.

Diabetic papillopathy in patients with optic disc drusen: Description of two different phenotypes.

PURPOSE: To describe two cases of severe acute bilateral optic disc edema that occurred in patients with diabetes mellitus shortly after the initiation of intensified antihyperglycemic therapy. METHODS: Retrospective observational case report. CASE DESCRIPTION: Two patients with type 1 diabetes presented for routine retinopathy screening with asymptomatic optic disc edema. One case was bilateral, the other unilateral. Neither patient had visual complaints. Both patients' glycemia history was characterized by a recent bout of poor regulation and both had optic disc edema consistent with diabetic papillopathy in combination with prominent Optic disc drusen (ODD). The swelling that appeared to constitute the edematous diabetes-related component of the disease resolved within 10-12 weeks during which diabetes therapy was optimized. Visual field deficits were seen early on in both patients and had resolved to some extent in one patient after 9 months but persisted in the one affected eye in the other patient up to at least 30 months. CONCLUSION: Two cases of ODD-associated diabetic papillopathy were observed: One with classic, bilateral disc edema and minor visual field defects, the other with unilateral disc edema, severe visual field defects and a phenotype that resembled non-arteritic anterior ischemic optic neuropathy. The cases suggest that ODD may increase the risk of diabetic papillopathy, a condition that is associated with rapid glycemia reduction and crowded optic discs, which may combine to produce nerve fiber swelling and hypoperfusion with venous congestion in a compartment with limited room for expansion.

Peripapillary hyperreflective ovoid mass-like structures: Multimodal imaging-A review.

Peripapillary hyperreflective ovoid mass-like structures (PHOMS) are a laterally bulging herniation of distended axons into the peripapillary region above the level of Bruch's membrane opening. Increased use of enhanced depth imaging-optical coherence tomography (EDI-OCT) in our evaluation of the optic nerve head (ONH) and greater recognition of the vast range of optic nerve pathologies with which PHOMS is associated provides convincing evidence that PHOMS is not just buried optic disc drusen (ODD) as previously described. The frequent coexistence of PHOMS with ODD, papilloedema, anterior ischaemic optic neuropathy, tilted optic disc syndrome, inflammatory demyelinating disorders and other diseases associated with axoplasmic stasis provides insight into its underlying pathophysiology. The present review will discuss the role of key imaging modalities in the differential diagnosis of PHOMS, explore the current literature on the relationship between PHOMS and common neuro-ophthalmic conditions, and highlight the gaps in our knowledge, with respect to disease classification and prognosis, to pave the way for future directions of research.

MFRP variant results in nanophthalmos, retinitis pigmentosa, variability in foveal avascular zone.

BACKGROUND: Membrane frizzled-related protein (MFRP) plays a critical role in ocular development. MFRP mutations are known to cause nanophthalmos and, in some cases, retinitis pigmentosa, foveoschisis, and/or optic nerve head (ONH) drusen. The broad clinical spectrum of MFRP mutations necessitates further investigation of specific genotype-phenotype relationships. MATERIALS AND METHODS: We reviewed ophthalmologic and genetic medical records of two affected siblings and one unaffected sibling. RESULTS: Genetic testing revealed variants MFRP c.855T>A, p.(Cys285*) and MFRP c.1235T>C, p.(Leu412Pro) in trans in the two affected siblings. In both cases, photopic and scotopic responses were markedly reduced on electroretinogram (ERG), with greater decrease in scotopic function. Optical coherence tomography for both siblings revealed non-cystoid thickening. Blunted foveal reflexes were also observed in both siblings. Notably, foveal avascular zone abnormalities were seen on fundus autofluorescence in only one affected sibling. CONCLUSIONS: MFRP-related ocular disease may be underrecognized due to its presentation with high hyperopia and possibly subtle retinal findings. Presence of variants MFRP c.855T>A, p.(Cys285*) and MFRP c.1235T>C, p.(Leu412Pro) in trans resulted in nanophthalmos and retinitis pigmentosa without associated foveoschisis or ONH drusen in our patients, consistent with the incomplete phenotype previously described in Neri et al. Abnormalities in the foveal avascular zone have been noted in other case studies and were inconsistently associated with the variants described here, representing a potential area for future investigation.

Bilateral Optic Nerve Head Drusen Complicated by Choroidal Neovascularization Misdiagnosed as Papilledema and Neuroretinitis.

We report a case of bilateral optic nerve head drusen complicated by choroidal neovascularization (CNV) in the left eye at presentation. The presence of optic disc and macular edema in addition to exudation led to the misdiagnosis of neuroretinitis at an outside medical center. Swept-source optical coherence tomography (SS-OCT) and SSOCT angiography were critical in establishing the diagnosis and follow-up in a noninvasive manner. Secondary CNV associated with optic nerve head drusen responded well to intravitreal injections of anti-vascular endothelial growth factor in the left eye. Asymptomatic nonexudative CNV that developed in the right eye during follow-up regressed spontaneously without treatment. [Ophthalmic Surg Lasers Imaging Retina 2022;53:518-521.].

An overview of peripapillary hyperreflective ovoid mass-like structures.

PURPOSE OF REVIEW: The purpose of this review is to provide an overview of the ophthalmic findings associated with peripapillary hyperreflective ovoid mass-like structures (PHOMS) in both adult and pediatric patients. RECENT FINDINGS: PHOMS have recently been identified in a number of different ophthalmic disease entities ranging from nonpathologic to pathologic, including but not limited to anatomic abnormalities (tilting in myopia), optic nerve head drusen, optic disc edema from inflammation (optic neuritis, white dot syndromes), vascular insults (ischemic optic neuropathy, retinal vascular occlusion), and papilledema. The mechanism underlying the formation of PHOMS has not been fully elucidated although it has been hypothesized that PHOMS occur secondary to axoplasmic stasis from crowding at the optic nerve head. SUMMARY: Although the clinical significance of the presence of PHOMS remains unclear, PHOMS are associated with several disease processes. Understanding the mechanism behind their formation and their impact on optic nerve head structure and visual function may be relevant in patients with optic nerve head pathology. The presence of PHOMS may also correlate with disease severity and duration. Future studies to evaluate whether the formation of PHOMS may be useful as an early indicator of disease or a prognostic tool are warranted.

Optic Disc Drusen in Patients With Ocular Hypertension: A Case Series and Review of the Literature.

BACKGROUND: The identification of glaucomatous optic neuropathy in the setting of optic disc drusen (ODD) is a challenge, and the decision of whether to offer treatment in the form of intraocular pressure (IOP) reduction is controversial. Here, we present a series of patients with coexisting ocular hypertension and ODD to evaluate clinical features, treatment options, and progression of optic neuropathy. In addition, a review of the literature on ODD with elevated IOP is provided. METHODS: Six patients with ODD and a history of ocular hypertension are presented. Components of the examination and imaging modalities used to establish the diagnosis of ODD were recorded and a description of ocular hypertension history, glaucoma testing, and the potential treatment of IOP were also provided. RESULTS: In this series, 4 of 6 patients with concurrent ocular hypertension and ODD showed progression of optic neuropathy as assessed by visual field or retinal nerve fiber layer thickness. Of the 2 patients who did not show evidence of progression, 1 was treated with IOP-lowering medications and 1 was observed off treatment. Of the 4 patients who showed evidence of progression, all 4 were initially treated with IOP-lowering medications and 2 ultimately went on to have trabeculectomy surgery. In the patients with progressive optic neuropathy, lowering the IOP seemed to halt the progression suggesting there was a pressure-sensitive component. CONCLUSIONS: Distinguishing changes to the optic nerve, particularly the structural changes at the lamina cribrosa of true glaucomatous optic neuropathy in the setting of ODD, is a challenge. Careful consideration of risk factors including age, presenting features, progression indicators, and management goals is to be accounted for in the decision to offer treatment. We see the presence ODD in the patients with ocular hypertension as an additional risk for progressive changes to the nerve fiber layer and visual field that needs to be considered when determining whether to initiate therapy. Our data suggest that treatment of IOP in the patients with ocular hypertension with ODD and evidence of progression reduces the risk of further progression. Further work is needed to determine whether progression of optic neuropathy in the setting of coexisting ODD and ocular hypertension is related mechanistically to predominantly an ODD-type process, a glaucomatous process, or a combination thereof.

Optic Nerve Head Anatomy and Vascular Risk Factors in Patients With Optic Disc Drusen Associated Anterior Ischemic Optic Neuropathy.

PURPOSE: Optic disc drusen (ODD) is an anatomical risk factor for nonarteritic anterior ischemic optic neuropathy (NA-AION). This study aimed to investigate the anatomical and vascular risk factors of patients with ODD-AION (ODD-associated NA-AION) and compare them with similar data from patients with nODD-AION (NA-AION without ODD). DESIGN: Case-control study. METHODS: Thirty-four ODD-AION and 34 nODD-AION patients who had all been systematically optical coherence tomography scanned using a standardized ODD scanning protocol were retrospectively analyzed and compared regarding demographics, vascular risk factors, clinical characteristics, and specific optic nerve head anatomical characteristics. RESULTS: In patients with ODD-AION, the ODD were predominantly deeply located (82%) but with no significant difference in size (52% large, 48% small). When compared with nODD-AION patients, ODD-AION patients were significantly younger at the time of diagnosis (P = .012) and had fewer vascular risk factors (P = .015). The ODD-AION patients had significantly more peripapillary hyperreflective ovoid mass-like structures (PHOMS) (P < .001) and prelaminar hyperreflective lines (P < .001) as well as smaller Bruch's membrane opening diameters (P = .017) compared with nODD-AION patients. No significant differences were found between ODD-AION and nODD-AION patients regarding visual acuity, refraction, lamina cribrosa position, ganglion cell layer volume, or retinal nerve fiber layer thickness. CONCLUSION: In ODD-AION, location of the ODD within the optic nerve head is important, while the size of the ODD is not. The ODD-AION and nODD-AION patients presented with distinctly different vascular risk factors and anatomical characteristics, establishing ODD and potentially also PHOMS as independent risk factors for developing NA-AION.

Juxtapapillary Choroidal Neovascular Membrane as a Complication of Optic Disc Drusen: Multimodal Imaging With Swept Source-Optical Coherence Tomography and Optical Coherence Tomography Angiography.

ABSTRACT: A 55-year-old Caucasian man presented to the neuro-ophthalmology department for follow-up evaluation due to long-standing bilateral optic nerve head drusen (ONHD). On examination, the BCVA was 20/20-2 in both eyes. Dilated fundus examination revealed extensive ONHD in both eyes, retinal hemorrhages, exudates inferonasal to the macula, and macular edema inferotemporal to the disc margin. Automated visual field testing revealed generalized depression in both eyes. Late phase leakage was observed on fluorescein angiography (FA). Optical coherence tomography angiography identified a small juxtapapillary choroidal neovascular membrane inferonasal to the macula in the right eye correlating with the area of retinal hemorrhage and exudates.