Fundoscopy use in neurology departments and the utility of smartphone photography: a prospective prevalence and crossover diagnostic accuracy study amongst neurology inpatients.

BACKGROUND AND PURPOSE: Although fundoscopy is a crucial part of the neurological examination, it is challenging, under-utilized and unreliably performed. The aim was to determine the prevalence of fundus pathology amongst neurology inpatients and the diagnostic accuracy of current fundoscopy practice compared with systematic screening with smartphone fundoscopy (SF) and portable non-mydriatic fundus photography (NMFP). METHODS: This was a prospective cross-sectional surveillance and diagnostic accuracy study on adult patients admitted under neurology in an Australian hospital. Inpatients were randomized to initial NMFP (RetinaVue 100, Welch Allyn) or SF (D-EYE) followed by a crossover to the alternative modality. Images were graded by neurology doctors, using telemedicine consensus neuro-ophthalmology NMFP grading as the reference standard. Feasibility parameters included ease, comfort and speed. RESULTS: Of 79 enrolled patients, 14.1% had neurologically relevant pathology (seven, disc pallor; one, hypertensive retinopathy; three, disc swelling). The neurology team performed direct ophthalmoscopy in 6.6% of cases and missed all abnormalities. SF had a sensitivity of 30%-40% compared with NMFP (45.5%); however, it had a lower rate of screening failure (1% vs. 13%, p < 0.001), a shorter examination time (1.10 vs. 2.25 min, p < 0.001) and a slightly higher patient comfort rating (9.2 vs. 8/10, p < 0.001). CONCLUSION: Our study demonstrates a clinically significant prevalence of fundus pathology amongst neurology inpatients which was missed by current fundoscopy practices. Portable NMFP screening appears more accurate than SF, whilst both are diagnostically superior to routine fundoscopic practice, feasible and well tolerated by patients.

Acute disseminated encephalomyelitis with bilateral optic neuritis following ChAdOx1 COVID-19 vaccination.

BACKGROUND: Acute disseminated encephalomyelitis (ADEM) is a rare immune-mediated inflammatory demyelinating disease of the central nervous system. We report a case of ADEM presenting with bilateral optic neuritis temporally associated with the ChAdOx1 vaccine against SARS-COVID19 virus. CASE PRESENTATION: A 36-year-old female presented with bilateral optic neuritis following her first dose of the ChAdOx1 vaccine. Initial MRI Brain showed evidence of demyelination within the subcortical white matter, with no radiological involvement of the optic nerves. Visual evoked potentials were consistent with bilateral optic neuritis which was confirmed radiologically on follow up MRI. She was treated with intravenous steroids with improvement both in symptoms and radiological appearance. A pseudo-relapse occurred which was treated with a further course of intravenous steroids followed by an oral taper. The clinical, radiological and serological results were most consistent with diagnosis of ADEM. CONCLUSIONS: ADEM is an exceedingly rare complication of ChAdOx1 vaccine despite millions of doses. While it is imperative clinicians remain aware of neurological complications of vaccines, the importance of vaccination to control a pandemic should not be undermined.

Ophthalmological consequences of cyanotic congenital heart disease: vascular parameters and nerve fibre layer.

BACKGROUND: This study investigated the long-term ophthalmological consequences of cyanotic congenital heart disease (CHD). DESIGN: Cross-sectional study, tertiary referral setting. PARTICIPANTS: Thirteen adults with cyanotic CHD (40 ± 4 years). Age- and sex-matched healthy controls underwent aspects of the protocol. METHODS: Cyanosed subjects had a full ophthalmic examination, visual fields, scanning laser ophthalmoscopy and optical coherence tomography to assess retinal nerve fibre layer (RNFL), retinal photography and cerebral magnetic resonance imaging (MRI). MAIN OUTCOME MEASURES: RNFL thickness and quantitative analysis of retinal vessels with fractal dimension, branching and central retinal arterial equivalent (CRAE) and central retinal venous equivalent (CRVE). RESULTS: No abnormalities of anatomy, motility, intraocular pressure or anterior segments were detected apart from one subject who had bilateral cataracts. Corrected visual acuity was normal in all but one cyanosed subject. Clinical examination revealed dilated retinal vasculature in 12/13 cyanosed subjects and increased tortuosity in 8/13. In the setting of cyanosis, skeletonized retinal arterial and venous beds had higher fractal dimension and increased branching (P ≤ 0.01, n = 11 for all); retinal vessels were dilated (CRAE: 227 vs. 183, n = 11, P < 0.0001; CRVE: 254 vs. 221, n = 11, P = 0.01). Visual fields showed scotomas in two subjects associated with RNFL thinning. No disc oedema was detected. 6/13 subjects' RNFL thickness fell below the normal 95% confidence interval in at least one sector without explanatory cerebral pathology (P < 0.0001, n = 13). Mean RNFL thickness correlated with MRI cerebral white matter volume (R = 0.67, P = 0.035). CONCLUSIONS: Cyanosed subjects had vessel dilatation, increased branching and tortuosity. RNFL and visual field thresholds were reduced suggesting impaired neuro-ophthalmological functioning.

Widespread endotheliopathy in adults with cyanotic congenital heart disease.

INTRODUCTION: Cyanotic congenital heart disease is associated with functional limitation and vascular events. The nature and extent of endothelial dysfunction in cyanotic adults is poorly understood. We sought to characterise endothelial function in this setting. METHODS: A total of fourteen adults with cyanotic congenital heart disease (40±3 years) together with age- and sex-matched healthy controls underwent assessment of nitric oxide-dependent vascular responses, including flow-mediated dilatation of the brachial artery and dynamic vessel analysis of the retina in response to flickering light. Plasma levels of the endothelium-derived vasoconstrictor endothelin-1 and the nitric oxide antagonist, asymmetric dimethylarginine, were measured. Circulating endothelial progenitor cells were assessed by flow cytometry. RESULTS: Flow-mediated dilatation was significantly lower in cyanosed adults than controls (4.0±0.8 versus 7.2±1.0%, p=0.019, n=11 per group). Retinal arterial and venous dilatory responses were also impaired (2.9±0.8 versus 5.0±0.6%, p=0.05 and 3.4±0.3 versus 5.2±0.7%, p=0.04, n=13). Serum levels of endothelin-1 and asymmetric dimethylarginine were higher in cyanosed adults (3.0±0.6 versus 1.1±0.1 pg/ml, p=0.004 and 0.68±0.05 versus 0.52±0.02 µmol/L, p=0.03, n=11). Endothelial progenitor cells (CD34+CD45dimCD133+KDR+) were reduced in those with chronic cyanosis (17±4 versus 40±6 per million white blood cells, p=0.005, n=11). CONCLUSIONS: Endothelial function is impaired in the systemic arteries and retinal vessels in adults with cyanotic congenital heart disease, suggesting a widespread endotheliopathy. Diminished numbers of endothelial progenitor cells might potentially contribute to these observations.

Spontaneous retinal venous pulsatility in patients with cyanotic congenital heart disease.

Spontaneous retinal venous pulsations (SRVP) are assessed as a clinical marker for patients with ophthalmic or neurological disorders. The pulsations are influenced by intraocular pressure (IOP), cerebrospinal fluid pressure (CSFp), and retinal venous pressure (RVP). However, little is known about the effect of cyanosis with polycythemia, a common finding in adults with complex congenital heart disease (CHD), on SRVP. This study investigated 11 subjects with long-standing cyanosis secondary to CHD and 11 control subjects to determine if there were measurable differences in resting pulsatility for a given IOP level. Intraocular pressure was measured using Goldman tonometry, and dynamic SRVP was recorded noninvasively using a retinal vessel imaging system. Peak amplitude of SRVP at each cardiac cycle was measured and compared with IOP. Heart rate was also monitored during the tests. Results show that for a similar baseline IOP, SRVP amplitudes are significantly lower in cyanotic patients compared with normal subjects (P < 0.0001). This may be explained by an increased RVP or high CSFp in these patients. Mean venous diameter is also significantly higher in cyanotic patients (P < 0.01), but no significant relationship was found between SRVP or diameter with blood parameters.

Correlation of structural retinal nerve fibre layer parameters and functional measures using Heidelberg Retinal Tomography and Spectralis spectral domain optical coherence tomography at different levels of glaucoma severity.

BACKGROUND: To compare the structure/function relationship in glaucoma cases at different levels of severity, and with different disc sizes, between the Heidelberg Retinal Tomography and Spectralis spectral domain optical coherence tomography. DESIGN: Retrospective study of glaucoma patients attending a Sydney-based private practice. PARTICIPANTS: 169 eyes of 169 patients with a clinical diagnosis of glaucoma. METHODS: Patients were divided on visual field criteria into early (mean deviation > -4 dB), moderate (-4 dB < mean deviation < -10 dB) and severe (mean deviation < -10 dB) disease. Bivariate correlation (Spearman's rho) between mean threshold scores for each area and the corresponding mean retinal nerve fibre layer thickness sectoral measurement were calculated. MAIN OUTCOME MEASURES: Correlation, as measured by Spearman's rho, between retinal nerve fibre layer measurements and mean threshold scores. Comparison of correlation strengths between the two scanning modalities with analysis of the effect of disease severity and disc size. RESULTS: Both imaging techniques showed only moderate correlations at best. Spectral domain optical coherence tomography (global retinal nerve fibre layer Spearman's rho = 0.670, P < 0.01) had higher correlation coefficients compared with Heidelberg Retinal Tomography rim area (Spearman's rho = 0.449, P < 0.01) and retinal nerve fibre layer (Spearman's rho = 0.421, P < 0.01). Disc size did not have a significant influence on the structure/function relationship. CONCLUSIONS: Spectral domain optical coherence tomography retinal nerve fibre layer measurements demonstrated closer correlations to visual field threshold reductions using a structure/function model in varying stages of glaucoma.

Bruch's Membrane Opening Minimum Rim Width Provides Objective Differentiation between Glaucoma and Nonglaucomatous Optic Neuropathies.

PURPOSE: A challenging clinical scenario is distinguishing between normal tension glaucoma (NTG) and non-glaucomatous optic neuropathies (NGON). The key to the assessment remains identifying the presence of optic nerve head cupping. Recent optical coherence tomography (OCT) measurements now allow objective assessment of cupping by minimum rim width at Bruch's membrane opening (MRW-BMO). This study assessed the hypothesis that the MRW-BMO measurement quantifies cupping and therefore can differentiate between NTG and NGON. DESIGN: Diagnostic evaluation with area under the curve. METHODS: Setting: multicenter tertiary hospitals and outpatient clinics. PATIENT POPULATION: 81 eyes of 81 patients were enrolled, 27 with NTG and 54 with NGON, including ischemic optic neuropathy, previous optic neuritis, and compressive and inherited optic neuropathies. All NGON patients with intraocular pressure >21 mm Hg, narrow drainage angles, or a family history of glaucoma were excluded. Observational procedure: optic disc OCT images were obtained of both the retinal nerve fiber layer thickness and the MRW-BMO. MAIN OUTCOME MEASUREMENTS: the utility of the MRW-BMO in differentiating GON from NGON was assessed using the area under the curve (AUC) estimated from a logistic regression model. RESULTS: The 5-fold cross-validated AUC for glaucoma versus nonglaucoma from logistic regression models using MRW-BMO values from all sectors was 0.95 (95% confidence interval: 0.86-1.00). CONCLUSIONS: The measurement of MRW-BMO effectively differentiates between NTG and NGON with a high level of sensitivity and specificity. Incorporating this measurement into routine glaucoma assessment may provide a robust method of assisting clinicians to improve diagnosis and therefore treatment of optic nerve diseases.

Identifying preperimetric functional loss in glaucoma: a blue-on-yellow multifocal visual evoked potentials study.

PURPOSE: To determine the ability of blue-on-yellow multifocal visual evoked potentials (BonY mfVEP) to identify functional loss in preperimetric glaucoma. DESIGN: Prospective case series. PARTICIPANTS: Thirty patients with glaucomatous optic discs and normal standard visual fields. METHODS: All patients underwent BonY mfVEP, dilated optic disc stereophotography, and optical coherence tomography (Fast RNFL protocol). Optic disc photographs were assessed by 2 independent examiners in a masked fashion. MAIN OUTCOME MEASURES: The mfVEP amplitude asymmetry and latency values were analyzed and compared topographically with findings of disc assessment. Average retinal nerve fiber layer (RNFL) thickness, RNFL asymmetry, and sectors with RNFL thinning were compared between patients with and without mfVEP defects. RESULTS: Fourteen (46.7%) patients demonstrated significant abnormality on amplitude asymmetry deviation plots of BonY mfVEP. In all 14 cases, the defect was monocular and corresponded to the eye with the worse disc. In 13 of 14 patients, the defect also corresponded to the location of the worst affected rim. Average RNFL thickness of eyes with mfVEP defects was 81.2+/-9.9 microm, significantly lower than that of patients without defects (90+/-10.5 microm; P = 0.035). Mean asymmetry of RNFL (better minus worse eye) also was significantly higher for patients with mfVEP defects compared with those without such defects (9.0+/-6.4 microm vs. 3.0+/-7 microm; P = 0.03). Average latency of both eyes of glaucomatous patients was delayed compared with that of controls, with no difference in latency between worse and better eyes of glaucoma patients. There was no association of latency delay with either the location of disc changes or mfVEP amplitude defects. CONCLUSIONS: Amplitude asymmetry of the BonY mfVEP seems to be a promising tool to identify functional loss in preperimetric glaucoma. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Dynamic association between intraocular pressure and spontaneous pulsations of retinal veins.

PURPOSE: The amplitude of spontaneous retinal venous pulsations (SRVP) is known to be affected by intraocular pressure (IOP), retinal venous pressure, and intracranial pressure (ICP). This study characterized SRVPs adjacent to the disc and quantified changes in the amplitude of these pulsations during IOP manipulation in normal subjects. METHODS: The study included 12 subjects (40 ± 15, 4 females, 8 males). Baseline IOP (range 10-25 mmHg) was measured and SRVP recorded using the dynamic retinal vessel analyzer (DVA). IOP was lowered using aproclonidine 0.5% and measured every 15 min, followed by dynamic recording of SRVP. Two subjects were also tested with timolol 0.5%, and three were treated with a placebo drop. Mean amplitude of SRVP was determined within each sample at the same site. Blood pressure and heart rate were tracked continuously. RESULTS: Amplitude of SRVP decreased in all subjects with reduction of IOP with aproclonidine and timolol. Mean SRVP amplitude was 8.5 ± 6 µm at baseline and reduced to 2.5 ± 1.8 µm after 45 min (p < 0.0001). IOP fell from 14.4 ± 2.6 mmHg to 10.2 ± 2.9 mmHg over the same period (p < 0.001). Venous diameter, blood pressure, and heart rate did not change significantly from the baseline. Analysis of waveforms showed a slight phase shift only (150 ± 78.5 ms, p = 0.93) between disc veins and adjacent retinal vein. CONCLUSION: SRVPs in the peripapillary retina have similar waveform characteristics to those at the disc. SRVP amplitudes are reduced by manipulation of IOP downwards with pharmacological intervention. The relationship was consistent in all individuals tested for two classes of drugs and was independent of BP or heart rate changes.

Dichoptic suppression of mfVEP amplitude: effect of retinal eccentricity and simulated unilateral visual impairment.

PURPOSE: To investigate the effect of retinal eccentricity on the phenomenon of dichoptic suppression of the mfVEP amplitude and to examine the relationship between the degree of simulated unilateral visual impairment and the possible release of dichoptic suppression in the contralateral eye. METHOD: Eight subjects with corrected visual acuity (VAc) >6/6 and stereoacuity >60 sec arc underwent monocular and dichoptic pattern-pulse mfVEP. Dichoptic stimulation was repeated with refractively induced blur of one eye with +4-D and +6-D lenses above distance correction. RESULTS: Dichoptic recording resulted in significant reduction of averaged mfVEP amplitude (19.8% ± 4.9%, paired t-test, P = 0.00003). The magnitude of suppression, while statistically significant at all eccentricities, was significantly larger in the central part of the visual field and diminished toward the periphery. Refractive blur, used to simulate visual impairment produced variable degrees of amplitude reduction in the blurred eye and resulted in amplitude increases in the contralateral eye. There was a highly significant correlation between the magnitude of amplitude reduction in the blurred eye and increase in amplitude (i.e., release of dichoptic suppression) in the contralateral eye (r = 0.91, P < 0.0001). CONCLUSIONS: The study demonstrated that dichoptic stimulation results in eccentricity-dependent suppression of mfVEP amplitude. Factors affecting visual performance of one eye (monocular blur) promote the release of dichoptic suppression in the fellow (unaffected) eye. This phenomenon leads to an increase in intereye asymmetry and therefore may improve early detection of ocular diseases, especially monocular pathologic processes.