Case Report: A Case of Cotton-Wool Spots After Intravitreal Injection of Conbercept in an Infant With Incontinentia Pigmenti

Introduction: Incontinentia pigmenti (IP) is a rare X-linked neuroectodermal dysplasia affecting multiple organs. One of its most significant ophthalmic manifestations is retinal neovascularization due to retinal ischemia, which has been traditionally treated with laser photocoagulation or cryotherapy. The application of anti-vascular endothelial growth factor (VEGF) has been reported for the treatment of retinopathy of IP with beneficial results. However, clinicians should be aware of the possible ocular and systemic side effects of the intravitreal injection of anti-VEGF agents.Case Report: A 4-month-old female infant with IP was treated with intravitreal injection of conbercept in both eyes. However, cotton-wool spots were noticed in the left eye 1 week after the injection. Laser photocoagulation was performed as an adjunct treatment. The cotton-wool spots were absorbed 1 month after the first intravitreal injection and have eventually disappeared.Discussion: The cotton-wool spots, after intravitreal injection of conbercept for the treatment of IP, indicated severe retinal ischemia resulting from the neutralization of excessive VEGF, which was shown on fundus photograph and fluorescent angiography. Anti-VEGF agents could cause retinal arteriolar vasoconstriction and artery occlusion on rare occasions. The administration of anti-VEGF agents in pediatric cases with severe neovascularization and retinal ischemia should be carefully considered.

Natural and iatrogenic ocular manifestations of rheumatoid arthritis: a systematic review

Purpose To provide an overview of the ocular features of rheumatoid arthritis (RA) and of the ophthalmic adverse drug reactions (ADRs) that may be associated with the administration of antirheumatic drugs. Methods A systematic literature search was performed using the PubMed, MEDLINE, and EMBASE databases. In addition, a cohort of 489 RA patients who attended the Authors’ departments were examined. Results Keratoconjunctivitis sicca, episcleritis, scleritis, peripheral ulcerative keratitis (PUK), and anterior uveitis were diagnosed in 29%, 6%, 5%, 2%, and 10%, respectively, of the mentioned cohort. Ocular ADRs to non-steroidal anti-inflammatory drugs are rarely reported and include subconjunctival hemorrhages and hemorrhagic retinopathy. In patients taking indomethacin, whorl-like corneal deposits and pigmentary retinopathy have been observed. Glucocorticoids are frequently responsible for posterior subcapsular cataracts and open-angle glaucoma. Methotrexate, the prototype of disease-modifying antirheumatic drugs (DMARDs), has been associated with the onset of ischemic optic neuropathy, retinal cotton-wool spots, and orbital non-Hodgkin’s lymphoma. Mild cystoid macular edema and punctate keratitis in patients treated with leflunomide have been occasionally reported. The most frequently occurring ADR of hydroxychloroquine is vortex keratopathy, which may progress to “bull’s eye” maculopathy. Patients taking tofacitinib, a synthetic DMARD, more frequently suffer herpes zoster virus (HZV) reactivation, including ophthalmic HZ. Tumor necrosis factor inhibitors have been associated with the paradoxical onset or recurrence of uveitis or sarcoidosis, as well as optic neuritis, demyelinating optic neuropathy, chiasmopathy, and oculomotor palsy. Recurrent episodes of PUK, multiple cotton-wool spots, and retinal hemorrhages have occasionally been reported in patients given tocilizumab, that may also be associated with HZV reactivation, possibly involving the eye. Finally, rituximab, an anti-CD20 monoclonal antibody, has rarely been associated with necrotizing scleritis, macular edema, and visual impairment. Conclusion The level of evidence for most of the drug reactions described herein is restricted to the “likely” or “possible” rather than to the “certain” category. However, the lack of biomarkers indicative of the potential risk of ocular ADRs hinders their prevention and emphasizes the need for an accurate risk vs. benefit assessment of these therapies for each patient.

Posterior segment manifestations and imaging features of COVID-19

Background: To report the posterior segment (uvea and retinal) manifestations and imaging characteristics of eyes of patients with and after coronavirus disease 2019 (COVID-19).Methods: We searched the PubMed/MEDLINE database to identify relevant articles using the following search terms: COVID-19, SARS-CoV-2, retina, uvea, optic nerve, retinal findings, posterior segment manifestations, and endophthalmitis. Articles published from December 1, 2019, to May 30, 2021, and indexed in PubMed/MEDLINE were screened.Results: For the purpose of this review, we included clinical features of 26 case reports and 8 case series. The posterior segment manifestations reported included cotton wool spots, retinal hemorrhages, central serous retinopathy, papillophlebitis, optic neuritis, panuveitis, multifocal retinitis, necrotizing retinitis, central retinal artery/vein occlusion, and Purtschner like retinopathy. In this review, we have also included optical coherence tomography angiography (OCTA) features that have been described in COVID-19 patients with pneumonia.Conclusions: COVID-19 patients can experience uveo-retinal manifestations even after recovery. These patients, even if asymptomatic for eye symptoms, should undergo an eye evaluation to rule out posterior segment involvement. OCTA performed in these patients revealed microvascular changes in the superficial and deep retinal plexuses. Some of these patients may require anticoagulant or antiplatelet therapy.

Safety, tolerability, pharmacokinetics, and pharmacodynamics of oral JNJ-64794964, a TLR-7 agonist, in healthy adults

Background This Phase I, two-part, first-in-human study assessed safety/tolerability and pharmacokinetics/pharmacodynamics of single-ascending doses (SAD) and multiple doses (MD) of the oral toll-like receptor-7 agonist, JNJ-64794964 (JNJ-4964) in healthy adults. Methods In the SAD phase, participants received JNJ-4964 0.2 ( N = 6), 0.6 ( N = 6), 1.25 ( N = 8) or 1.8 mg ( N = 6) or placebo ( N = 2/dose cohort) in a fasted state. Food effect was evaluated for the 1.25 mg cohort following ≥6 weeks washout. In the MD phase, participants received JNJ-4964 1.25 mg ( N = 6) or placebo ( N = 2) weekly (fasted) for 4 weeks. Participants were followed-up for 4 weeks. Results No serious adverse events (AEs) occurred. 10/34 (SAD) and 5/8 (MD) participants reported mild-to-moderate (≤Grade 2), transient, reversible AEs possibly related to JNJ-4964. Five (SAD) participants had fever/flu-like AEs, coinciding with interferon-α serum levels ≥100 pg/mL and lymphopenia (<1 × 109/L), between 24–48 h after dosing and resolving approximately 96 h after dosing. One participant (MD) had an asymptomatic Grade 1 AE of retinal exudates (cotton wool spots) during follow-up, resolving 6 weeks after observation. JNJ-4964 exhibited dose-proportional pharmacokinetics, with rapid absorption (tmax 0.5–0.75 h) and distribution, and a long terminal half-life (150–591 h). Overall, no significant differences in JNJ-4964 pharmacokinetic parameters were observed in the fed versus fasted state. JNJ-4964 dose-dependently and transiently induced cytokines with potential anti-HBV activity, including interferon-α, IP-10, IL-1 RA, and/or MCP-1, and interferon-stimulated genes (ISG15, MX1, and OAS1) in serum. Conclusions In healthy adults, JNJ-4964 was generally well-tolerated, exhibited dose-proportional pharmacokinetics and induced cytokines/ISGs, with possible anti-HBV activity.

Severe COVID-19 and Retina: Are There Any Retinal Manifestations?

Purpose To investigate whether there are retinal lesions associated with severe COVID-19. Methods We studied 232 symptomatic subjects aged 18 – 65 years who had severe COVID-19 and had received treatment. The evaluations included ophthalmological examinations, optical coherence tomography (OCT), imaging modalities with near infrared reflectance (NIR), fundus autofluorescence (FAF), and fundus photography (FP). Results The mean age of the patients was 49 years, and 67.6% of them were men. There were no findings of microhemorrhage, cotton wool spots (CWS), vitritis, or retinitis in the examination and imaging. Conclusions This study indicates that retinal involvement as a complication associated with COVID-19 is questionable, although some reports have demonstrated a relationship that may occur secondary to existing systemic diseases.

A Case of Onset and Treatment on Purtscher’s Retinopathy in a Single Eye

Background:Purtscher’s retinopathy is an occlusive microvasculopathy caused by traumatic injuries, especially like head and chest injuries. The exact mechanism of injury remains unclear, and Most case reports about Purtscher’s retinopathy focused on the symptoms of fundus, and did not provide detailed medical treatments. Case presentation: In this case, the patient suffered suddenly vision loss in the right eye one day after a traffic accident with moderate head and chest injuries. Ocular examinations revealed typical characteristics of cotton wool spots, and minimal intraretinal hemorrhages around the optic disc. 5 different drugs were used in this patient. 15 days after the treatment (corticosteroids and traditional Chinese medicine), the vision of the patient was improved and the symptoms (cotton wool spots, hemorrhages, retinal edema and visual field) were alleviated obviously. Conclusions: Corticosteroids and traditional Chinese medicines used in our case did improve the vision of the patient, and alleviated the symptoms of fundus.

Cerebral malaria: insight into pathology from optical coherence tomography

We aimed to investigate structural retinal changes in malarial retinopathy (MR) using hand-held optical coherence tomography (HH-OCT) to assess its diagnostic potential. Children with MR (n = 43) underwent ophthalmoscopy, fluorescein angiography and HH-OCT during admission, 1-month (n = 31) and 1-year (n = 8) post-discharge. Controls were comatose patients without malaria (n = 6) and age/sex-matched healthy children (n = 43). OCT changes and retinal layer thicknesses were compared. On HH-OCT, hyper-reflective areas (HRAs) were seen in the inner retina of 81% of MR patients, corresponding to ischaemic retinal whitening on fundus photography. Cotton wool spots were present in 37% and abnormal hyper-reflective dots, co-localized to capillary plexus, in 93%. Hyper-reflective vessel walls were present in 84%, and intra-retinal cysts in 9%. Vascular changes and cysts resolved within 48 h. HRAs developed into retinal thinning at 1 month (p = 0.027) which was more pronounced after 1 year (p = 0.009). Ischaemic retinal whitening is located within inner retinal layers, distinguishing it from cotton wool spots. Vascular hyper-reflectivity may represent the sequestration of parasitized erythrocytes in vessels, a key CM feature. The mechanisms of post-ischemic retinal atrophy and cerebral atrophy with cognitive impairment may be similar in CM survivors. HH-OCT has the potential for monitoring patients, treatment response and predicting neurological deficits.

Cotton-wool spots, red-lesions and hard-exudates distinction using CNN enhancement and transfer learning

<div>The automatic retinal disease diagnosis by artificial intelligent is an interesting and challenging topic in the medical field. It requires an appropriate image enhancement technique and a sufficient training dataset for the specific retina conditions. The aim of this study was to design an automatic diagnosis convolutional neural network (CNN) model which does not require a large training dataset to specifically identify diabetic retinopathy symptoms, which are cotton wool, exudates spots and red lesionin colour fundus pictures. A novel framework comprised image enhancement method by using upgraded contrast limited adaptive histogram equalization (UCLAHE) filter and transferred pre-trained networks was developed to classify the retinal diseases regarding to the symptoms. The performance of the proposed framework was evaluated based on accuracy, sensitivity and specificity metrics. The collected results have proven the robustness of the proposed framework in offering good accuracy in retina diseases diagnosis. </div>

Retinal Microcirculation as a Correlate of a Systemic Capillary Impairment After Severe Acute Respiratory Syndrome Coronavirus 2 Infection

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), affects the pulmonary systems via angiotensin-converting enzyme-2 (ACE-2) receptor, being an entry to systemic infection. As COVID-19 disease features ACE-2 deficiency, a link to microcirculation is proposed. Optical coherence tomography angiography (OCT-A) enables non-invasive analysis of retinal microvasculature. Thus, an impaired systemic microcirculation might be mapped on retinal capillary system. As recent OCT-A studies, analyzing microcirculation in two subdivided layers, yielded contrary results, an increased subdivision of retinal microvasculature might offer an even more fine analysis. The aim of the study was to investigate retinal microcirculation by OCT-A after COVID-19 infection in three subdivided layers (I). In addition, short-term retinal affections were monitored during COVID-19 disease (II). Considering (I), a prospective study (33 patientspost−COVID and 28 controls) was done. Macula and peripapillary vessel density (VD) were scanned with the Spectralis II. Macula VD was measured in three layers: superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP). Analysis was done by the EA-Tool, including an Anatomical Positioning System and an analysis of peripapillary VD by implementing Bruch's membrane opening (BMO) landmarks. Overall, circular (c1, c2, and c3) and sectorial VD (s1-s12) was analyzed. Considering (II), in a retrospective study, 29 patients with severe complications of COVID-19 infection, hospitalized at the intensive care unit, were monitored for retinal findings at bedside during hospitalization. (I) Overall (p = 0.0133) and circular (c1, p = 0.00257; c2, p = 0.0067; and c3, p = 0.0345). VD of the ICP was significantly reduced between patientspost−COVID and controls, respectively. Overall (p = 0.0179) and circular (c1, p = 0.0189) peripapillary VD was significantly reduced between both groups. Subgroup analysis of hospitalized vs. non-hospitalized patientspost−COVID yielded a significantly reduced VD of adjacent layers (DCP and SVP) with increased severity of COVID-19 disease. Clinical severity parameters showed a negative correlation with VD (ICP) and peripapillary VD. (II) Funduscopy yielded retinal hemorrhages and cotton wool spots in 17% of patients during SARS-CoV-2 infection. As VD of the ICP and peripapillary regions was significantly reduced after COVID-19 disease and showed a link to clinical severity markers, we assume that the severity of capillary impairment after COVID-19 infection is mapped on retinal microcirculation, visualized by non-invasive OCT-A.