Risk of newly developing visual field defect and neurodegeneration after pars plana vitrectomy for idiopathic epiretinal membrane
Akino K, Nagai N, Watanabe K, et al. Risk of newly developing visual field defect and neurodegeneration after pars plana vitrectomy for idiopathic epiretinal membrane. Br J Ophthalmol. 2021 Dec;105(12):1683–1687. doi: 10.1136/bjophthalmol-2020-317478
Idiopathic epiretinal membranes are found in as many as 4% of adults over the age of 40 years. Consequently, pars plana vitrectomy, with or without peeling of the internal limiting membrane (ILM), is becoming an increasing frequent surgical procedure. The authors analysed the data of 30 patients who developed visual field defects (VFDs) following the procedure.
Thirty eyes of 30 patients who had normal preoperative visual fields (SITA 30–2 programme) were included in the study. The authors assessed the impact of ILM peeling on the risk of developing a VFD. They also looked at changes in the thickness of each retinal neural layer to help determine the pathogenesis of these defects. Seventeen of the eyes underwent peeling of the ILM and 28 eyes received Brilliant Blue G staining during surgery.
Twenty-two eyes (73.3%) developed VFDs following pars plana vitrectomy. These patients were more likely to have undergone simultaneous cataract surgery (59.1%), peeling of the ILM (77.3%) and the use of Brilliant Blue G staining (100%). For most patients (86.4%), the VFDs were located in the nasal field, most commonly (63.6%) in the superior nasal quadrant.
Optical coherence tomography (OCT) obtained in these patients showed a thickening of the ganglion cell layer in patients who did not develop a VFD. On the other hand, patients who acquired a VFD showed a 10.7 µm decrease in retinal ganglion cell layer thickness, primarily in the temporal retina.
OCT was also correlated with peeling of the ILM. They found that patients who underwent ILM peeling suffered an 18.6 µm decrease in retinal nerve fibre layer thickness and an 11.1 µm reduction in ganglion cell layer thickness. Patients who did not undergo ILM peeling showed increases in both measurements.
The ILM is the basement membrane for Müller glial cells. The authors postulate that stripping of the ILM injures the Müller cells thereby disrupting the homoeostasis of the neural microenvironment. There may also be a mechanical stress to the neurons at the time of peeling.
Peeling the ILM at the time of surgery for an epiretinal membrane has been shown to decrease the rate of recurrence of the membrane. However, one should consider the possibility of creating a VFD in these patients.
David A. Bellows
Optic neuritis as the initial presentation in the MSBase registry
Kenney R, Liu M, Patil S, et al. Long-term outcomes in patients presenting with optic neuritis: Analyses of the MSBase registry. J of Neurol Sci. 2021;430:118067 doi: 10.1016/j.jns.2021.118067
This multi-centre retrospective observational cohort study aimed to evaluate the long-term trajectory in clinically isolated syndrome (CIS) patients with optic neuritis (ON) as the first clinical demyelinating event and determine the association of treatment with sustained expanded disability status scale (EDSS) score and visual function score (VFS) over time. From the international dataset, the MSBase registry, they identified 1317 subjects from 60933 patients from 41 centres with a baseline visit after 1995 (introduction of the first multiple sclerosis [MS] disease modifying therapy in Europe).
After excluding 198 patients who converted to clinically definite MS (CDMS) within 3 months of onset, 741 (66.2%) of the 1119 CIS patients converted to CDMS with a median time from enrolment to the cohort of 1.0 (range 0.3–17.7) years. As compared to 50% of ON patients developing MS at the 15-year follow-up in the Optic Neuritis Treatment Trial (ONTT), this higher frequency of conversion is likely due to difference in study designs as well as ascertainment patterns between the ONTT and MSBase Registries.
The results from this study also showed that treatment with disease modifying therapies may delay onset and reduce the risk of conversion to CDMS, sustained EDSS progression and sustained VFS progression in CIS patients with ON onset. Recent discussions of the International Panel on Diagnosis of MS addressed the inclusion of the optic nerve as a fifth magnetic resonance imaging lesion site in the diagnostic criteria for MS. Although the optic nerve was not incorporated in the 2017 revisions to the McDonald Criteria, the committee discussed obtaining more data to justify the inclusion. The authors commented that these CIS patients would have been diagnosed earlier upon inclusion of optic nerve lesions for dissemination in space and time. According to their study results, such patients may benefit from better preservation of visual and physical function upon earlier treatment with MS disease-modifying therapies. Nevertheless, it is important to beware of misdiagnosing MS after a monophasic acute ON given the presence of other mimickers such as neuromyelitis optica spectrum disorder and myelin oligodendrocyte antibody disease.
In terms of disease modifying agents, no difference in VFS or EDSS progression was identified between high potency and low potency treatment groups. Twelve percent of subjects in this observational study sustained visual disability. This study also highlights the difference in VFS and EDSS for reflection of visual function as VFS relies heavily on high-contrast visual acuity measurements while EDSS scoring is heavily based on ambulatory function. High-contrast acuity may under-estimate the true amount of disability following ON and thus may under-estimate the effects of treatment.
Noel C.Y. Chan
Red desaturation is more common in normal individuals than we thought
Mikolajczyk B, Ritter A, Larson C, et al. Red desaturation prevalence and severity in healthy patients. Neurology: Clinical Practice 12.1 (2022): 1–5. doi: 10.1212/CPJ.0000000000001011
Red desaturation is common after optic neuropathies and therefore testing for relative red desaturation between eyes is often used in clinical practice to provide evidence of a prior unilateral optic neuropathy, especially optic neuritis. However, the prevalence of asymmetrical red desaturation has not been examined in a normal population. Therefore, the authors recruited 101 adults with a normal eye examination who were asked if they perceived a difference in the redness of a red tropicamide bottle cap between their two eyes and to estimate the interocular percentage difference if present. Strikingly, 24 (23.8%) reported some degree of red desaturation with an average interocular difference of 9% (range 2–25%). There was no statistical relationship between red desaturation and race, sex, or age.
The limitations of this study include the sample size of 101 patients, which may be too small to detect differences in race, sex, or age. Furthermore, this study did not evaluate the percentage difference of red desaturation in patients with optic nerve pathology and therefore the degree of red desaturation may still be a helpful clinical test.
In summary, this study is important because it shows that nearly a quarter of healthy individuals have some degree of asymmetrical red desaturation. This means that the specificity of the red desaturation test for asymmetrical optic neuropathy may not be as high as we had thought. Future studies will be helpful to determine if there is a threshold that is helpful for separating pathological from physiological red desaturation.
John J. Chen
Papilloedema and venous sinus thrombosis from vaccine-induced thromboticthrombocytopaenia.
Qian J, Lutchman C, Margolin E. Papilloedema due to vaccine-induced thrombocytopenia. Ophthalmology. 2022 Feb;129(2): 190. doi:10.1016/j.ophtha.2021.07.016
The authors report a case of a 45-year-old woman who developed papilloedema and venous sinus thrombosis 8 days after receiving the AstraZeneca vaccine for COVID-19. The patient also had a pulmonary embolism and bilateral adrenal haemorrhage. She was found to be thrombocytopaenic and had a positive heparin-induced thrombocytopaenia assay leading to a diagnosis of vaccine-induced thrombotic thrombocytopaenia. She was treated with argatroban, immunoglobulins, and hydrocortisone. Ophthalmologists should be aware of this rare phenomenon that can occur with these vaccines.
John J. Chen
Dual phase Valsalva-augmented computed tomography angiography may help to delineate the draining path of orbital vascular malformations
Roelofs KA, Duckwiler G, Gundlach B, et al. Orbital vascular malformations: determining outflow with Valsalva manoeuvre-augmented computed tomography angiography. Ophthalmology. 12 January 2022;S0161-6420(222)00003–3. doi: 10.1016/j.ophtha.2022.01.003.
The authors conducted a retrospective study to investigate if findings on dynamic dual phase Valsalva-augmented computed tomography angiography (CTA) can predict which orbital vascular malformation (VMs) drain directly to the cavernous sinus (CS), which may allow pre-operative optimisation of the embolisation technique. They enrolled nine patients with orbital VMs, who received both dual-phase Valsalva CTA and conventional venography (CV). They found that lesions with direct drainage to the CS tended to be located much closer to the orbital apex (p = .008). On dual-phase Valsalva CTA, the ipsilateral superior ophthalmic vein (SOV) tended to show a greater increase in size with Valsalva in lesions draining directly to the CS. In addition, patients with direct drainage to the CS were more likely to have an absolute change in SOV asymmetry of ≥ 0.5 mm (p = .048). The authors concluded that Valsalva CTA may be a minimally invasive imaging study that can be performed as part of the work-up and planning process for orbital VMs.
Hui-Chen Cheng
Charles Bonnet syndrome-related symptoms may happen in patients with late age-related macular degeneration and impact quality of life
Le JT, Peprah D, Agron E, et al. Associations between age-related eye diseases and Charles Bonnet syndrome in participants of the age-related eye disease study 2: Report Number 26. Ophthalmology. 2022 Feb;129(2):233–235. doi: 10.1016/j.ophtha.2021.08.012.
Using 10-year data from the Age-Related Eye Disease Study 2 (AREDS2), the authors described the prevalence and characteristics of Charles Bonnet syndrome (CBS) among older adult participants and examined associations between two age-related eye conditions (late age-related macular degeneration [AMD] and cataract surgery). Certified interviewers assessed participants for CBS symptoms at trial close-out and at the end of the follow-up period. Of 3651 AREDS2 participants who had responded to CBS-related questions, 12% (446/3651) reported having experienced CBS symptoms. The majority of these had late AMD (86%) or cataract surgery (64%) in one or both eyes by 10 years. Most (68%) had best-corrected visual acuity < 20/40 in the worse eye at trial close-out. Having late AMD (odds ratio [OR], 1.95) or cataract surgery (OR, 1.42) was associated with reporting CBS symptoms. Reporting CBS symptoms was associated with having depressive symptoms (OR, 1.51) but not with cognitive impairment. The authors concluded that CBS-related symptoms, while often not functionally disabling, can be distressing and impact quality of life. These findings may support a call to raise awareness for the need for detection and management of CBS in the ophthalmology community.
Hui-Chen Cheng
Multimodal imaging features of optic disc drusen
Yan Y, Ludwig CA, Liao YJ. Multimodal imaging features of optic disc drusen. Am J Ophthalmol. 2021;225:18–26. doi: 10.1016/j.ajo.2020.12.023.
The authors aimed to identify key en face multimodal imaging features of optic disc drusen (ODD). This study was a retrospective, cross-sectional study of 61 eyes from 38 patients with ODD and high quality enhanced depth imaging-optical coherence tomography (EDI-OCT), en face fundus autofluorescence (FAF) and near-infrared reflectance (NIR) imaging. The latter two provide intuitive assessment of the entire optic disc in one image compared with EDI-OCT, potentially making it less time-intensive and experience-dependent for physicians to evaluate.
The en face multimodal imaging modalities included: (1) blue-light FAF; (2) green-light FAF; (3) NIR imaging; and (4) colour fundus imaging. The EDI-OCTs were acquired using either Cirrus HD-OCT or Spectralis Heidelberg Retina Angiograph plus OCT in EDI mode. Two reviewers independently graded FAF, NIR and colour fundus images from each patient to reach a mutual consensus.
The authors found that on EDI-OCT, ODD appeared as one or multiple masses with signal-poor cores and hyper-reflective anterior margins of various sizes in the unmyelinated optic nerve, usually in the nasal portion, with 83% being above and below Bruch’s membrane opening. On green-light FAF, the ODD were homogenously bright, while on blue-light FAF they were heterogeneous. On en face NIR, ODD appeared grey, often associated with the appearance of “pearls”, “bubbles” or “super-bright dots” which can be helpful additional features to make the diagnosis. Overall, green-light FAF had the highest sensitivity for detecting ODD, followed by blue-light FAF, NIR and then colour fundus photos.
The authors recommended that green-light FAF can be a simple, non-mydriatic screening test for ODD. If this was negative and a high suspicion remained then EDI-OCT could be considered next.
The limitations of this study include its retrospective and cross-sectional design, which limited standardisation of some of the parameters including OCT source and FAF measurements. The average age in this study was 29-years-old, and there could be differences in younger versus older populations, given we know that ODD can migrate with age. Future studies evaluating changes in visual fields would also be useful.
Peter W. MacIntosh
Invasive fungal sinusitis in patients with coronavirus disease 2019 seen in South India
Hema VK, Kumar K, Shah VM. Invasive fungal sinusitis in patients with coronavirus disease 2019 seen in South India. J Neuroophthalmol. 6 January 2022. doi: 10.1097/WNO.0000000000001516.
The authors retrospectively reviewed the electronic medical records of 10 patients affected with COVID-19 disease who presented with cranial nerve palsies at the neuro-ophthalmology department of a tertiary eye care hospital in South India. Most of the patients presented with multiple cranial nerve palsies with poor visual acuity. Six were from fungal involvement while four were thought to be inflammatory. Two of the 10 cases succumbed to death due to the intracranial involvement. All cases had uncontrolled diabetes mellitus with a history of systemic corticosteroids, and neuroimaging of these cases showed sinusitis of varying severity, most of which were suggestive of fungal invasive type. The authors emphasised the need to screen for fungal involvement in COVID-19 cases presenting with multiple cranial nerve palsies, especially in diabetic patients treated with systemic corticosteroids.
Michael S. Vaphiades
Paraneoplastic neuromyelitis optica spectrum disorder associated with lung adenocarcinoma: a case report
Maiorca C, Moret F, Martines V, et al. Paraneoplastic neuromyelitis optica spectrum disorder associated with lung adenocarcinoma: a case report. Front Med (Lausanne). 2022;8:743798. doi: 10.3389/fmed.2021.743798
Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disease affecting the central nervous system, which most commonly causes optic neuritis, transverse myelitis, and area postrema syndrome. Antibodies directed against aquaporin 4, a water channel expressed on the astrocytic membrane, are detected in approximately 80% of cases. In this article, the authors discuss a case of a 76-year-old woman with a 2-month history of confusion, dysarthria, and progressive bilateral leg weakness, which was associated with adenocarcinoma. They conclude that signs of NMOSD in elderly patients should arouse the suspicion of a paraneoplastic aetiology.
Michael S. Vaphiades
COVID-19-Associated optic neuritis – A case series and review of literature
Jossy A, Jacob N, Sarkar S, Gokhale T, Kaliaperumal S, Deb AK. COVID-19-associated optic neuritis – A case series and review of literature. Indian J Ophthalmol. 2022;70:310–316. doi: 10.4103/ijo.IJO_2235_21
Only a few reports have been published describing COVID-19-associated neuro-ophthalmological manifestations. The authors present a series of three cases, each of whom developed optic neuritis during the recovery period from COVID-19 infection. Among these three patients, demyelinating lesions were identified in two cases, while another case was associated with serum antibodies against myelin oligodendrocyte glycoprotein. All three patients received intravenous methylprednisolone and visual recovery was noted in all patients, which was maintained at 2 months. The authors add to the sparse body of literature regarding the neuro-ophthalmological manifestations of COVID-19 infections.
Michael S. Vaphiades
Stroke risk before and after central retinal artery occlusion: A population-based analysis
Chodnicki KD, Tanke LB, Pulido JS, Hodge DO, Klaas JP, Olsen TW, Bhatti MT, Chen JJ. Stroke risk before and after central retinal artery occlusion: a population-based analysis. Ophthalmology. 2022 Feb;129(2):203–208. doi:10.1016/j.ophtha.2021.07.017
The authors sought to determine the risk of stroke, transient ischaemic attack (TIA), and transient monocular vision loss (TMVL) before and after a central retinal artery occlusion (CRAO) in a population-based, retrospective case series of 89 patients with CRAO. The study demonstrated that the risk of symptomatic ischaemic stroke was 2.2% in the 15 days before and after a CRAO, which is slightly lower than most studies from tertiary centres. They concluded that these data should be considered as practice recommendations are developed regarding the urgency of neurovascular workup in patients with acute CRAO.
Michael S. Vaphiades
Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis
Bjornevik K, Cortese M, Healy BC, et al. Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis. Science. 21 January 2022;375(6578):296–301. doi: 10.1126/science.abj8222
The authors tested the hypothesis that multiple sclerosis (MS) is caused by Epstein-Barr virus (EBV) in a cohort comprising more than 10 million young adults on active duty in the United States military, 955 of whom were diagnosed with MS during their period of service. The risk of MS increased 32-fold after infection with EBV but was not increased after infection with other viruses, including the similarly transmitted cytomegalovirus. Serum levels of neurofilament light chain, a biomarker of neuroaxonal degeneration, increased only after EBV seroconversion. The authors concluded that the findings cannot be explained by any known risk factor for MS and suggested EBV as the leading cause of MS.
Michael S. Vaphiades
The best course of action
Vaphiades MS, Nudleman E. The best course of action. Surv Ophthalmol. 2022 Mar-Apr;67(2):623–627. doi:10.1016/j.survophthal.2021.01.013.
The authors report an 11-year-old girl who noted gradual visual loss in the right eye for 1 year to 20/100 in the right eye, compared with 20/20 in the left eye, with subfoveal yellow deposits in both eyes. Optical coherence tomography, electro-oculography, electro-retinography and colour fundus photographs illustrate the findings,which were in-keeping with Best’s disease, the second most common hereditary macular dystrophy. It is characterised by the accumulation of lipofuscin-like materials on the retinal pigment epithelium cell-photoreceptor interface. The disorder’s associated mutations may contribute to apoptosis of the retinal pigment epithelial cells by targeting Caspase-3 (a protein encoded by the CAPS3 gene) that may be one of the mechanisms in bestrophinopathies.
Michael S. Vaphiades
Ocular syphilis
Furtado JM, Simões M, Vasconcelos-Santos D, et al. Ocular syphilis. Surv Ophthalmol. 2022 Mar-Apr;67(2):440–462. doi: 10.1016/j.survophthal.2021.06.003.
Multiple studies around the world suggest that syphilis is re-emerging. It has become an increasingly common cause of ocular inflammation over the past 20 years. Ocular syphilis has a wide range of presentations, most of which are subtypes of uveitis, although, vitritis and papillitis are also common. Optic disc involvement may occur in isolation or associated with other retinal or vitreal signs, or conversely as retrobulbar or optic perineuritis. The authors review the demographics, epidemiology, clinical features, ocular imaging findings, diagnosis, and medical management of ocular syphilis
Michael S. Vaphiades
Sildenafil in ophthalmology: An update
Arora S, Surakiatchanukul T, Arora T, Cagini C, Lupidi M, Chhablani J. Sildenafil in ophthalmology: An update. Surv Ophthalmol. 2022 Mar-Apr;67(2):463–487. doi: 10.1016/j.survophthal.2021.06.004.
Sildenafil citrate, a selective oral phosphodiesterase 5 inhibitor, is a widely used drug for erectile dysfunction that acts by elevating cyclic guanosine monophosphate levels and causing smooth muscle relaxation. It also has 10% activity against phosphodiesterase 6, a key enzyme in the phototransduction cascade in the retina. Recent ocular imaging developments have further revealed the influence of sildenafil on ocular haemodynamics, particularly choroidal perfusion. Choroidal thickness is increased, and choroidal perfusion is also enhanced by autoregulatory mechanisms that are further dependent on age and microvascular abnormalities. Studies demonstrating high intraocular pressure via a “parallel pathway” from increased choroidal volume and blood flow to the ciliary body have challenged previous concepts. Another new observation is the effect of sildenafil on bipolar cells and cyclic-nucleotide gated channels. The authors discuss potential deleterious effects (central serous chorioretinopathy, glaucoma, ischaemic optic neuropathy, and risks to recessive carriers of retinitis pigmentosa), potential beneficial effects (amelioration of choroidal ischaemia, prevention of thickening of Bruch membrane, and promotion of recovery of the ellipsoid zone) in macular degeneration, as well as potential drug interactions of sildenafil.
Michael S. Vaphiades
FLAIR is more sensitive than the T1 sequence for early diagnosis of Susac’s syndrome
Bellanger G, Biotti D, Adam G, et al. Leptomeningeal enhancement on post-contrast FLAIR images for early diagnosis of Susac syndrome. Mult Scler. 2022 Feb;28(2):189–197. doi: 10.1177/13524585211012349.
Background: Leptomeningeal enhancement (LME) is included in the latest diagnostic criteria of Susac’s syndrome (SuS) but is only occasionally depicted on post-contrast T1-weighted imaging (T1-WI). As post-contrast fluid-attenuated inversion recovery (FLAIR) may be more sensitive, the aim of this study was to assess LME on FLAIR images and to explore its diagnostic value in SuS. Methods: The authors conducted a retrospective study of 20 patients with a definite SuS diagnosis from 2010 to 2020. Two radiologists independently assessed the number of areas of LME on post-contrast FLAIR and T1-WI acquisitions performed before any treatment. A chi-square test was used to compare both sequences and the inter-rater agreement was calculated. Results: Thirty-five magnetic resonance imaging (MRI) sessions were performed before treatment, including 19 post-contrast FLAIR images in 17 patients and 25 post-contrast T1-WIs in 19 patients. In terms of patients, LME was observed on all 17 post-contrast FLAIR images versus 15/19 (79%) of post-contrast T1-WIs (p < .05). In terms of sequences, LME was observed on all post-contrast FLAIR images versus 16/25 (64%) of post-contrast T1-WIs (p < .005). LME was disseminated at both supratentorial (19/19) and infratentorial (18/19) levels on post-contrast FLAIR, compared with post-contrast T1-WI (3/25 and 9/25, respectively). Inter-rater agreement was excellent for post-contrast FLAIR (κ = 0.95) but only moderate for post-contrast T1-WI (κ = 0.61). Conclusion: The authors concluded that LME was always observed and easily visible on post-contrast FLAIR images prior to SuS treatment. In association with other MRI features, it is highly indicative of SuS.
Comments: This new image finding of higher diagnostic sensitivity by the FLAIR sequence with contrast for early stage of SuS compared with the more commonly used T1-WI sequence, provides our clinicians especially Neuro-ophthalmologists, another MRI brain sequence to pay attention to while we suspect SuS and in the differential diagnosis of other central nervous system inflammatory and demyelinating conditions. One of the limitations of this study is the lack of a control group hence cannot information cannot be provided for the diagnostic specificity.
Xiaojun Zhang
Eye is the window to the soul: Retina on OCT correlated with cerebral cortex on MRI
Mizell R, Chen H, Lambe J, Saidha S, Harrison DM. Association of retinal atrophy with cortical lesions and leptomeningeal enhancement in multiple sclerosis on 7 T MRI. Mult Scler. 2022 Mar;28(3):393–405. doi: 10.1177/13524585211023343.
Background: Retinal atrophy in multiple sclerosis (MS), as measured by optical coherence tomography (OCT), correlates with demyelinating lesions and brain atrophy, but its relationship with cortical lesions (CLs) and meningeal inflammation is not well known. Objectives: To evaluate the relationship of retinal layer atrophy with leptomeningeal enhancement (LME) and CLs in MS as visualised on 7 Tesla (7 T) magnetic resonance imaging (MRI). Methods: Forty participants with MS underwent 7 T MRI of the brain and OCT. Partial correlation and mixed-effects regression evaluated relationships between MRI and OCT findings. Results: All participants had CLs and 32 (80%) participants had LME on post-contrast MRI. Ganglion cell/inner plexiform layer (GCIPL) thickness correlated with total CL volume (r = −0.45, p < .01). Participants with LME at baseline had thinner macular retinal nerve fibre layers (mRNFL; p = .01) and GCIPL (p < .01). Atrophy in various retinal layers was developed quicker with certain patterns of LME. For example, mRNFL declined – 1.113 (–1.974, – 0.252) μm/year faster in those with spread/fill-pattern LME foci at baseline compared with those without (p = .01). Conclusion: This study associates MRI findings of LME and cortical pathology with thinning of retinal layers as measured by OCT, suggesting a common link between meningeal inflammation, CLs, and retinal atrophy in MS.
Comments: OCT is certainly much cheaper and accessible than 7 T MRI. This finding provides more evidence and logic of using OCT as an additional tool for monitoring disability progression and worsening of cognitive function in MS patients.
Xiaojun Zhang