Amantadine-induced corneal edema: A case and literature review

Purpose: To present a case of irreversible corneal edema after 10 years of amantadine use. A literature review was carried out to describe the clinical characteristics and outcomes of amantadine-induced corneal edema. Observations: A 36-year-old woman presented with a 6-week history of gradually progressive bilateral painless visual loss with visual acuity (VA) of 20/350 and 20/300 in the right and left eye, respectively. Examination showed bilateral diffuse central corneal edema with multiple Descemet membrane folds without endothelial guttata, keratic precipitates or intraocular inflammation. This did not respond to hypertonic saline drops and empirical treatment for presumed herpetic endotheliitis with oral acyclovir. Medication review revealed the use of amantadine 100mg daily for the past 10 years, prescribed by her neurologist for fatigue. Despite discontinuing amantadine, corneal edema was irreversible due to a markedly reduced endothelial cell count of 625 (right) and 680 cells/mm2 (left). Conclusions and Importance: This case highlights the need to consider amantadine as a cause of unexplained bilateral non-guttae corneal edema. A literature review of 33 case reports revealed broadly similar features of amantadine-induced corneal edema; whilst most cases had favorable outcomes with median VA 20/25 (interquartile range IQR 20/20–20/30) and complete resolution of corneal edema within 30 days (IQR 14–35) of amantadine discontinuation, most experienced low endothelial cell density 759 cells/mm2 (IQR 621–1078). Taken together, screening specular microscopy ought to be considered for those in whom amantadine is likely required long-term

Optical Coherence Tomography Angiography-Confirmed Paracentral Acute Middle Maculopathy Associated With SARS-CoV-2 Infection

Retinal manifestations have been reported in Covid-19 patients including paracentral acute middle maculopathy (PAMM) and vasculitis.1-4 A case series of 12 visually asymptomatic Covid-19 patients reported inner retinal hyper-reflective bands despite normal optical coherence tomography angiography (OCT-A).1 Concerns about this report have been raised in another article.5 We describe the first case of OCT-A confirmed SARS-CoV-2-related PAMM

Electrophysiological Measures of Retinal Function Obtained With a Portable Device In Idiopathic Intracranial Hypertension Patients

The photopic negative response (PhNR) of the electroretinogram (ERG) derives from retinal ganglion cells. We recorded ERGs with a portable device in patients with idiopathic intracranial hypertension (IIH) exploring inter-ocular correlation

Humoral and cellular immunogenicity to a second dose of COVID-19 vaccine BNT162b2 in people receiving methotrexate or targeted immunosuppression : a longitudinal cohort study

Background: COVID-19 vaccines have robust immunogenicity in the general population. However, data for individuals with immune-mediated inflammatory diseases who are taking immunosuppressants remains scarce. Our previously published cohort study showed that methotrexate, but not targeted biologics, impaired functional humoral immunity to a single dose of COVID-19 vaccine BNT162b2 (Pfizer-BioNTech), whereas cellular responses were similar. Here, we aimed to assess immune responses following the second dose. Methods: In this longitudinal cohort study, we recruited individuals with psoriasis who were receiving methotrexate or targeted biological monotherapy (ie, tumour necrosis factor [TNF] inhibitors, interleukin [IL]-17 inhibitors, or IL-23 inhibitors) from a specialist psoriasis centre serving London and South-East England. The healthy control cohort were volunteers without psoriasis, not receiving immunosuppression. Immunogenicity was evaluated immediately before, on day 28 after the first BNT162b2 vaccination and on day 14 after the second dose (administered according to an extended interval regimen). Here, we report immune responses following the second dose. The primary outcomes were humoral immunity to the SARS-CoV-2 spike glycoprotein, defined as titres of total spike-specific IgG and of neutralising antibody to wild-type, alpha (B.1.1.7), and delta (B.1.617.2) SARS-CoV-2 variants, and cellular immunity defined as spike-specific T-cell responses (including numbers of cells producing interferon-γ, IL-2, IL-21). Findings: Between Jan 14 and April 4, 2021, 121 individuals were recruited, and data were available for 82 participants after the second vaccination. The study population included patients with psoriasis receiving methotrexate (n=14), TNF inhibitors (n=19), IL-17 inhibitors (n=14), IL-23 inhibitors (n=20), and 15 healthy controls, who had received both vaccine doses. The median age of the study population was 44 years (IQR 33–52), with 43 (52%) males and 71 (87%) participants of White ethnicity. All participants had detectable spike-specific antibodies following the second dose, and all groups (methotrexate, targeted biologics, and healthy controls) demonstrated similar neutralising antibody titres against wild-type, alpha, and delta variants. By contrast, a lower proportion of participants on methotrexate (eight [62%] of 13, 95% CI 32–86) and targeted biologics (37 [74%] of 50, 60–85; p=0·38) had detectable T-cell responses following the second vaccine dose, compared with controls (14 [100%] of 14, 77–100; p=0·022). There was no difference in the magnitude of T-cell responses between patients receiving methotrexate (median cytokine-secreting cells per 106 cells 160 [IQR 10–625]), targeted biologics (169 [25–503], p=0·56), and controls (185 [133–328], p=0·41). Interpretation: Functional humoral immunity (ie, neutralising antibody responses) at 14 days following a second dose of BNT162b2 was not impaired by methotrexate or targeted biologics. A proportion of patients on immunosuppression did not have detectable T-cell responses following the second dose. The longevity of vaccine-elicited antibody responses is unknown in this population. Funding: NIHR Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust and King's College London; The Psoriasis Association.</p

The effect of methotrexate and targeted immunosuppression on humoral and cellular immune responses to the COVID-19 vaccine BNT162b2 : a cohort study

Background: Patients on therapeutic immunosuppressants for immune-mediated inflammatory diseases were excluded from COVID-19 vaccine trials. We therefore aimed to evaluate humoral and cellular immune responses to COVID-19 vaccine BNT162b2 (Pfizer-BioNTech) in patients taking methotrexate and commonly used targeted biological therapies, compared with healthy controls. Given the roll-out of extended interval vaccination programmes to maximise population coverage, we present findings after the first dose. Methods: In this cohort study, we recruited consecutive patients with a dermatologist-confirmed diagnosis of psoriasis who were receiving methotrexate or targeted biological monotherapy (tumour necrosis factor [TNF] inhibitors, interleukin [IL]-17 inhibitors, or IL-23 inhibitors) from a specialist psoriasis centre serving London and South East England. Consecutive volunteers without psoriasis and not receiving systemic immunosuppression who presented for vaccination at Guy's and St Thomas' NHS Foundation Trust (London, UK) were included as the healthy control cohort. All participants had to be eligible to receive the BNT162b2 vaccine. Immunogenicity was evaluated immediately before and on day 28 (±2 days) after vaccination. The primary outcomes were humoral immunity to the SARS-CoV-2 spike glycoprotein, defined as neutralising antibody responses to wild-type SARS-CoV-2, and spike-specific T-cell responses (including interferon-γ, IL-2, and IL-21) 28 days after vaccination. Findings: Between Jan 14 and April 4, 2021, 84 patients with psoriasis (17 on methotrexate, 27 on TNF inhibitors, 15 on IL-17 inhibitors, and 25 on IL-23 inhibitors) and 17 healthy controls were included. The study population had a median age of 43 years (IQR 31–52), with 56 (55%) males, 45 (45%) females, and 85 (84%) participants of White ethnicity. Seroconversion rates were lower in patients receiving immunosuppressants (60 [78%; 95% CI 67–87] of 77) than in controls (17 [100%; 80–100] of 17), with the lowest rate in those receiving methotrexate (seven [47%; 21–73] of 15). Neutralising activity against wild-type SARS-CoV-2 was significantly lower in patients receiving methotrexate (median 50% inhibitory dilution 129 [IQR 40–236]) than in controls (317 [213–487], p=0·0032), but was preserved in those receiving targeted biologics (269 [141–418]). Neutralising titres against the B.1.1.7 variant were similarly low in all participants. Cellular immune responses were induced in all groups, and were not attenuated in patients receiving methotrexate or targeted biologics compared with controls. Interpretation: Functional humoral immunity to a single dose of BNT162b2 is impaired by methotrexate but not by targeted biologics, whereas cellular responses are preserved. Seroconversion alone might not adequately reflect vaccine immunogenicity in individuals with immune-mediated inflammatory diseases receiving therapeutic immunosuppression. Real-world pharmacovigilance studies will determine how these findings reflect clinical effectiveness. Funding: UK National Institute for Health Research.</p