BACKGROUND:Nonarteritic anterior ischemic optic neuropathy (NAION) or optic nerve stroke is the most common acute optic neuropathy in patients older than 50 years and results in severe vision loss. Endogenous flavoprotein fluorescence (FPF) imaging is a novel imaging modality to quantify axonal mitochondrial stress in the living central nervous system. We investigated the evolution of optic disc and macular FPF, and other ophthalmic measurements in the first 6 months after NAION onset. METHODS:We retrospectively analyzed 10 patients (15 eyes) with acute NAION and performed serial assessments of visual function, optic disc FPF, macular FPF, and spectral-domain optical coherence tomography for 6 months. Longitudinal trends in optic disc FPF and peripapillary retinal nerve fiber layer (pRNFL) were modeled using generalized additive models with random effects to account for repeated measures. Linear mixed-effects models were used to assess changes from baseline to the 2-4 and 5-7-month follow-up periods. RESULTS:In the acute phase (<45 days), pRNFL thickness was elevated, consistent with optic disc edema, while optic disc FPF values were within the normal range. Over time, optic disc FPF increased, and pRNFL thickness decreased, with relative stabilization after approximately 3 months, whereas visual acuity remained stable. Linear mixed-effects analysis of eyes with baseline imaging ≤45 days and follow-up at 2-4 months (5 eyes) and/or 5-7 months (6 eyes) demonstrated a significant increase in optic disc FPF (Δ = 5.77 dB, P < 0.001) and a significant decrease in pRNFL thickness by 2-4 months (Δ = -153.02 µm, P < 0.001), with no significant changes from the 2-4-month to the 5-7-month period. CONCLUSIONS:Optic disc FPF is normal in acute NAION because of masking by optic disc edema. As optic disc edema resolves, optic disc FPF score increases, reaching a plateau at around 3 months after onset, consistent with increased axonal metabolic stress.
Background: Evaluation and treatment of giant cell arteritis (GCA) is multidisciplinary, with high morbidity if not promptly treated. Ophthalmologists may be involved due to the presence of visual symptoms and/or ischemic vision loss. The goal of this study was to characterize the health care journey of patients suspected of having GCA and elucidate the role that ophthalmologists and other specialists play in their prebiopsy evaluation. Methods: This retrospective study included patients at a single large academic institution who underwent a temporal artery biopsy (TAB) as part of a GCA evaluation over a 10-year period. Demographics, symptoms, laboratory testing, ancillary imaging, treatment initiation, biopsy results, and final diagnosis were extracted from the medical record. Types of specialists involved in different aspects of the prebiopsy evaluation for GCA were tabulated. A Sankey plot was created to visualize the included patients' journeys. Results: Among 162 subjects undergoing TAB (average age of 74 years SD 11.3, 64.8% female, 60% ocular symptoms), 43 were diagnosed with GCA (30 positive TAB). Subjects saw an average of 3.31 providers (SD 1.15) from different specialties during their prebiopsy evaluation, with multiple patients seeing 6 different specialists. Within our cohort, 51% (n = 83) of patients saw ophthalmologists before TAB and 33% (n = 53) had their TAB performed by an ophthalmologist. Seeing an ophthalmologist during the prebiopsy period was not associated with a positive biopsy result ( P = 0.80) or prebiopsy steroid treatment for GCA ( P = 0.90). Conclusions: GCA suspects have a convoluted journey through our health care system and are commonly seen by multiple medical subspecialists during their evaluation. This may benefit patients due to multiple expert perspectives or may contribute to fragmentation of care and delays in treatment. These results reinforce the number of subspecialists, including ophthalmologists, who play a role in the evaluation of GCA. Multidisciplinary fast-track GCA clinics can both provide access to subspeciality care and simplify the patient journey.
BACKGROUND:Optic disc drusen (ODD), which can mimic papilledema and pose a diagnostic challenge to ophthalmologists, can be effectively detected using computed tomography (CT). In this retrospective study, we investigated how often radiologists report the presence of drusen on CT scans when the indication may not have been ODD. METHODS:This was a retrospective chart review of consecutive patients with ODD with previous brain CT scan performed for various unrelated reasons. The inclusion criteria included patients with fundus autofluorescence, or optical coherence tomography-enhanced depth imaging-proven ODD who already had CT scan done for any reason. RESULTS:Twenty-five CT scan reports from 23 patients (43 eyes; 17 women, 6 men) were included, with a mean age of 37.0 ± 19.2 years (range, 10-74). ODD were bilateral in 20 patients (87.0%) and unilateral in 3 (13.0%). Five CT scans were performed with contrast (20.0%) and 20 without contrast (80.0%). ODD were explicitly mentioned in only 8 of 25 reports (32.0%), despite being present in all patients. It was mentioned in all 5 scans performed for unrelated neuro-ophthalmic indications. CONCLUSIONS:In conclusion, ODD were underreported on CT scans, with only 32% of reports explicitly mentioning their presence. This has implications for radiologists, who should be aware of the importance of ODD to ophthalmologists, who may look back at previous CT scans. Ophthalmologists should be aware that the absence of an ODD mention in a CT report does not indicate the absence of ODD on the imaging.
BACKGROUND:Pulsations and pressure changes in the retinal vein are known to be implicated in glaucoma and are sensitive to changes in both intraocular and intracranial pressures (IOP and ICP). This study evaluates the feasibility and physiological concordance of estimating ICP from spontaneous retinal venous pulsation (SVP) thresholds using noninvasive negative-pressure (NP) goggles and comparing these estimates with reference ICPs measured through manometry during lumbar puncture (LP). METHODS:This prospective, single-center pilot study evaluated the capacity of the Ocular Pressure Adjusting Pump (OPAP) to aid in estimating ICP. Adults who were scheduled for clinically indicated LP underwent noninvasive IOP modulation with sealed negative-pressure goggles (OPAP) within 24 hours before LP. An increasing magnitude of NP was applied until SVP was extinguished. Masked examiners determined IOP at the last presence of SVP and first absence of SVP at the optic disc, as measured through the OPAP goggles. Predicted ICP was defined as the midpoint between those 2 IOP values. OPAP measurements were performed twice for each eye: once in an upright seated position and again in the left lateral decubitus (LLD) position. Agreements between OPAP-predicted and LP-measured ICPs were evaluated with a Bland-Altman analysis using 80% limits of agreement (LoA). RESULTS:Of 15 participants, 11 had visible SVPs that could be extinguished during NP application with OPAP and were included in the analysis. Four participants did not exhibit SVPs at baseline; all had LP-measured ICP exceeding IOP (mean ± SD: 17.6 ± 5.3 and 13.5 ± 1.1 mm Hg, respectively; P < 0.001). For eyes with measurable SVP thresholds, the mean OPAP-predicted ICP was 12.7 ± 3.2 mm Hg in an upright seated position and 17.5 ± 3.1 mm Hg in a lateral position. In the upright analysis, mean bias (predicted-reference ICP) was -0.17 mm Hg with 80% LoA ±6.19 Hg. In the lateral analysis, mean bias was +4.66 mm Hg with 80% LoA ±3.56 mm Hg. CONCLUSIONS:In this pilot feasibility study, SVP-threshold-derived ICP estimates demonstrated minimal bias when OPAP measurements were taken with patients in an upright position and systematic overestimation when OPAP measurements were taken with patients in the LLD position. Conversely, OPAP's ICP estimations demonstrated better consistency (narrower 80% LoAs) with measurements taken in the LLD as compared with upright measurements (wider 80% LoAs). These pilot study findings are exploratory in nature and are not intended to guide individual patient care. Larger studies with standardized positioning and contemporaneous reference measurements are required to define accuracy, identify sources of bias, and demonstrate clinical utility.
BACKGROUND:Current knowledge regarding the causes, clinical course, treatment response, and long-term outcomes of pediatric optic neuritis remains largely derived from case reports and retrospective series. Considering the ethnic variability in its presentation and the critical role of antibody-based differential diagnoses in guiding treatment strategies, further research is necessary. The aim of this study was to provide insights into the etiology and clinical findings of pediatric optic neuritis, thereby improving our knowledge of the condition in the era of antibody-based approaches. METHODS:This prospective multicenter cohort study was conducted at 31 referral medical centers. Patients younger than 18 years with first-episode optic neuritis were included. All patients underwent comprehensive neuro-ophthalmic examinations, including aquaporin-4-IgG and myelin oligodendrocyte glycoprotein-IgG testing and brain/orbit MRI. The primary outcome measure was best-corrected visual acuity (BCVA) at 6 months. Best-corrected visual acuity was further categorized into high vision (BCVA ≥ 20/40), moderate vision (20/200 < BCVA < 20/40), and low vision (BCVA ≤ 20/200). RESULTS:Overall, 44 pediatric patients were enrolled, with a mean age at onset of 10.7 ± 3.5 years. Bilateral optic neuritis and optic disc swelling were observed in 56.8% and 81.8% of patients, respectively. The mean BCVA at enrolment was 0.99 ± 0.89 logMAR, which improved significantly to 0.24 ± 0.52 logMAR at 6 months. The final 6-month diagnoses included myelin oligodendrocyte glycoprotein antibody-associated disease (n = 30 [68.2%]), isolated optic neuritis (n = 11 [25.0%]), acute disseminated encephalomyelitis (n = 2 [4.5%]), multiple sclerosis (n = 1 [2.3%]). No patients had neuromyelitis optica. At the 6-month follow-up, 50.0% showed improvement in the visual category, 50.0% maintained their visual category, and none experienced deterioration. There were no significant predictors related to poor BCVA at enrolment and at 6 months. CONCLUSION:Pediatric optic neuritis exhibits severe visual deficits but shows good recovery. Myelin oligodendrocyte glycoprotein antibody-associated disease is the most common etiology. These findings reflect the distinct characteristics of pediatric optic neuritis and provide important baseline data for developing tailored treatment strategies.
BACKGROUND:To evaluate the effects of systemic corticosteroid therapy on visual and structural outcomes in patients with nonarteritic anterior ischemic optic neuropathy (NA-AION) treated with systemic corticosteroids vs those untreated, using optical coherence tomography (OCT) and OCT angiography (OCTA). METHODS:This retrospective study included 72 subjects: 23 steroid-treated patients with NA-AION, 24 untreated patients, and 25 age- and sex-matched healthy controls. All participants underwent comprehensive ophthalmic evaluation, including best-corrected visual acuity (BCVA), visual field testing, OCT, and OCTA imaging. Macular and peripapillary vessel densities were quantitatively analyzed. Additional analyses using analysis of covariance (ANCOVA) were performed to adjust for baseline visual acuity, age, sex, and systemic comorbidities. RESULTS:Baseline BCVA did not differ significantly between the patient groups. Greater unadjusted improvement in visual acuity was observed in the steroid-treated group ( P = 0.031). However, after adjustment for baseline visual acuity and covariates, ANCOVA revealed only a borderline trend favoring steroid therapy (F(2,65) = 2.51, P = 0.089, partial η 2 =0.072). Similarly, mean deviation in visual field testing showed a modest but nonsignificant improvement after adjustment (F(1,30) = 2.19, P = 0.149, partial η 2 =0.068). OCT demonstrated significant thinning of the retinal nerve fiber layer and ganglion cell-inner plexiform layer in both NA-AION groups compared with controls, with no significant differences between treated and untreated patients. OCTA revealed reduced vessel density in all macular and peripapillary sectors in NA-AION eyes relative to controls ( P < 0.001), without significant intergroup differences. CONCLUSIONS:Systemic corticosteroid therapy in NA-AION may be associated with greater functional improvement in visual acuity and visual field parameters; however, these findings should be interpreted with caution given the influence of baseline visual acuity and the retrospective study design. The absence of corresponding differences in structural and vascular OCT and OCTA parameters suggests that any potential functional benefit may occur independently of measurable microvascular restoration. Further prospective, controlled studies are required to clarify the role of corticosteroids in the management of NA-AION.
BACKGROUND:Peripapillary hyper-reflective ovoid mass-like structures (PHOMS) are commonly observed in optic disc swelling of various etiologies, but the factors contributing to their formation have not been fully elucidated. This study aimed to investigate the association between the presence of PHOMS and optical coherence tomography (OCT) parameters in eyes with optic disc edema secondary to various diseases. METHODS:This retrospective study included patients who underwent orbital and head MRI to determine the underlying cause of optic disc edema at the Department of Ophthalmology, Kyoto University Hospital, between April 2018 and March 2024. The data of the patients with optic disc edema detected using swept-source OCT were included in the analysis. The scleral canal diameter (SCD), peripapillary choroidal thickness, and optic nerve head height were measured. The background characteristics and OCT parameters of the eyes with and without PHOMS were compared. The associations between PHOMS and OCT parameters were determined using univariable and multivariable regression analyses based on generalized estimation equations. RESULTS:Fifty-one eyes of 41 patients (22 males and 19 females) were included in this study. PHOMS were detected in 26 eyes (51%). Multivariable regression analysis revealed a trend toward an association between narrower SCD and increased risk of PHOMS, but the association was not statistically significant (β = -0.0028; 95% confidence interval, -0.49 to 0.91; P = 0.067). CONCLUSIONS:Narrower SCDs in eyes with optic disc edema were associated with a higher risk of developing PHOMS. The structural characteristics of the optic disc may play an important role in the development of PHOMS in eyes with secondary optic disc edema.
BACKGROUND:Previous studies have identified inequities in stroke epidemiology. Given retinal artery occlusion (RAO) is a stroke equivalent, we investigated risk factors and social determinants of health (SDOH) associated with RAO. METHODS:This was a retrospective case-control study. The case group consisted of all patients diagnosed with RAO in the National Institutes of Health All of Us database from November 1992 to November 2020. The control group consisted of all patients without a diagnosis of RAO during that time frame. Associations of predictors of RAO were estimated using logistic regression models. RESULTS:There were 384 patients with an RAO diagnosis and 328,639 participants in the non-RAO group. Median age at RAO diagnosis was 66 years (interquartile range [IQR] 57-72). Median age at study was 74 years (IQR 67-81) for the RAO group and 58 years (IQR 42-69) for the control group. Age- and sex-adjusted multivariable analysis revealed factors positively associated with RAO, including older age {odds ratio [OR]: 2.19 (95% confidence interval [CI]: 2.01-2.39), P < 0.001}, male sex (OR: 1.54 [95% CI: 1.25-1.89], P < 0.001), Black race (OR: 1.62 [95% CI: 1.24-2.09], P < 0.001), military/Veterans Affairs insurance (OR: 2.44 [95% CI: 1.61-3.66], P < 0.001), and Medicaid (OR: 1.51 [95% CI: 1.06-2.15], P = 0.022). Having a college/advanced degree (OR: 0.76 [95% CI: 0.59-0.98], P = 0.031), annual household income between $50,000 and $100,000 (OR: 0.72 [95% CI: 0.52-0.98], P = 0.035), and annual household income between $100,000 and $200,000 (OR: 0.48 [95% CI: 0.32-0.70], P < 0.001) were protective against RAO. CONCLUSIONS:These findings confirm previously described associations between RAO and cardiovascular comorbidities and identified novel associations between RAO and SDOH, including Black race and Medicaid insurance. Stroke risk around the time of RAO was high in this cohort.
BACKGROUND:This study describes the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of serum angiotensin-converting enzyme (s-ACE), and serum lysozyme in the diagnosis of sarcoid optic neuropathy (SON). METHODS:We retrospectively reviewed the electronic medical record (EMR) of adult patients evaluated by neuro-ophthalmologists at Froedtert Hospital and the Medical College of Wisconsin clinics with a diagnosis of optic neuropathy (ON) from January 1, 2012, through July 1, 2023, who had s-ACE and/or serum lysozyme levels assessed. Potential patients for inclusion were identified using institutional data search tools. We then manually reviewed the EMR of each patient to verify whether inclusion parameters were met, and to gather relevant demographic and clinical data including s-ACE and lysozyme levels, and ON etiology. For the diagnosis of "Probable" or "Definite" SON, we relied on previously published consensus criteria for the diagnosis of neurosarcoidosis from the Neurosarcoidosis Consortium Consensus Group. The sensitivity, specificity, PPV, and NPV of s-ACE and lysozyme in the diagnosis of SON were calculated. For patients determined to meet criteria for a diagnosis of SON, we extracted additional data from the EMR including tissue biopsy location/s and findings; whether sarcoidosis diagnosis was already established before presentation with ON; whether the patient was taking corticosteroids or ACE-inhibitor (ACE-I) therapy at the time of laboratory evaluation; cerebrospinal fluid ACE (CSF-ACE) level; results of chest imaging; and results of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET) scans. RESULTS:A total of 706 patients with ON were included. Of these 706 patients, 395 (56%) were women and 311 (44%) were men, with a median age of 51 years (range: 18-90). All 706 had an s-ACE level available, while 110 also had a lysozyme level available. Fourteen of the 706 (2%) patients met criteria for a diagnosis of "Probable" (n = 13) or "Definite" (n = 1) SON. Of these, 7 (50%) were women and 7 (50%) were men, with a median age of 42 years (range: 19-60). Seven of the 14 (50%) patients had a previously established diagnosis of sarcoidosis before presenting with ON. We found a sensitivity for s-ACE in diagnosing SON of 21.4%, and a specificity of 97%. The PPV of s-ACE was 12.5%, and the NPV was 98.4%. For lysozyme, we found a sensitivity of 33.3%, a specificity of 98%, PPV of 60%, and NPV of 94.3%. CONCLUSIONS:In diagnosing SON, we have found s-ACE to have a sensitivity of 21.4%, and a specificity of 97%. The PPV of s-ACE was 12.5% and the NPV was 98.4%. We have determined lysozyme in this setting to have a sensitivity of 33.3% and a specificity of 98%. The PPV of lysozyme was 60% and the NPV was 94.3%. The fact that s-ACE and lysozyme have low sensitivity for the diagnosis of SON indicates that neither of these tests is suitable as a general screening tool in this setting.
