Ophthalmic manifestations of Cryptococcus gattii species complex: a case series and review of the literature

AIM: To report 4 cases of Cryptococcus gattii (C. gattii) species complex infection with diverse ophthalmic manifestations, and to review the literature to examine pathobiology of disease, classical ophthalmic presentations and outcomes, and treatment modalities for this emerging pathogen. METHODS: Cases of C. gattii meningoencephalitis with ophthalmic manifestations were identified via chart review at two institutions in Australia and one institution in the mid-west region of the United States and are reported as a case series. Additionally, a MEDLINE literature review was conducted to identify all reported cases of C. gattii with ophthalmic manifestations from 1990-2020. Cases were reviewed and tabulated, together with our series of patients, in this report. RESULTS: Four cases of C. gattii with ophthalmic manifestations are presented; three from Australia and one from the USA. A literature review identified a total of 331 cases of C. gattii with visual sequelae. The majority of cases occurred in immunocompetent individuals. Blurred vision and diplopia were the most common presenting symptoms, with papilloedema the most common sign, reported in 10%-50% of cases. Visual loss was reported in 10%-53% of cases, as compared to rates of visual loss of 1%-9% in C. neoformans infection. Elevated intracranial pressure, cerebrospinal fluid (CSF) fungal burden, and abnormal neurological exam at presentation correlated with poor visual outcomes. The mainstays of treatment are anti-fungal agents and aggressive management of intracranial hypertension with serial lumbar punctures. CSF diversion procedures should be considered for refractory cases. Acetazolamide and mannitol are associated with high complication rates, and adjuvant corticosteroids have demonstrated higher mortality rates; these treatments should be avoided. CONCLUSION: Permanent visual loss represents a devastating yet potentially preventable sequelae of C. gattii infection. Intracranial hypertension needs to be recognised early and aggressively managed. Referral to an ophthalmologist/neuro-ophthalmologist in all cases of cryptococcal infection independent of visual symptoms at time of diagnosis is recommended.

Ophthalmic manifestations are associated with reduced tear lymphotoxin-α levels in chronic ocular graft-versus-host disease

Purpose To determine the role tear lymphotoxin-α (LT-α) in chronic ocular graft-versus-host disease (oGVHD). Methods Twenty-two chronic oGVHD and 17 control tear samples were collected, and commercial test strips were used to detect LT-α concentrations. Concentration differences between patients with and without oGVHD were determined via Mann-Whitney U test. The correlation between LT-α levels and ophthalmic parameters was analyzed using Spearman’s test. Results The concentration of LT-α was significantly lower in oGVHD patients than in controls. LT-α levels were significantly correlated with OSDI, NIH eye score, T-BUT, and CFS among all participants. ROC analysis revealed that the area under the curve of LT-α was 0.847, and the cutoff value for chronic oGVHD diagnosis was 0.203 ng/mL. Conclusion Our study revealed the significant decrease of tear LT-α in oGVHD, and suggested LT-α as a promising marker for chronic oGVHD diagnosis.

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.

Epidemiology of disease-activity related ophthalmological manifestations in Systemic Lupus Erythematosus: A systematic review

Objective Ophthalmic complications in Systemic Lupus Erythematosus (SLE) are broad and can occur in up to a third of patients. The British Isles Lupus Assessment Group (BILAG) 2004 Index identifies 13 ocular manifestations of active SLE, as opposed to those related to previous disease activity and/or the consequences of therapy. We conducted a systematic review of published literature to determine the frequency of ophthalmic manifestations of active SLE. Methods A systematic literature search of Ovid MEDLINE and EMBASE from their respective inceptions to July 2020 was conducted to identify cohort, case–control and cross-sectional studies. Results 22 studies meeting eligibility criteria were included. Most studies featured small sample sizes and were judged to have a high risk of methodological bias. The number and quality of studies did not allow us to confidently estimate the incidence of the conditions. No studies reported epidemiological data for orbital inflammation/myositis/proptosis. The prevalence of each of the other ocular manifestations, with the exception of retinal vaso-occlusive disease, was consistently less than 5%. Retinal vasculitis, uveitis and isolated cotton wool spots tended to be associated with more active SLE disease. Conclusion The prevalence of eye disease due to SLE activity is uncommon, but clinicians should be aware that some conditions tend to be associated with more active systemic disease. Further studies to determine the incidence and risk factors for these ophthalmic manifestations are needed.

Gyrate Atrophy of the Choroid and Retina: A Review

Gyrate atrophy (GA) of the choroid and retina is a rare autosomal recessive genetic condition characterized by elevation of the plasma level of the amino acid ornithine due to deficiency of the enzyme ornithine ketoacid aminotransferase. Accumulation of ornithine occurs in various body tissues but leads primarily to characteristic ophthalmic manifestations including myopia, cataract, progressive chorioretinal atrophy, and macular changes. Patients usually present with night blindness that starts in the first decade of life followed by visual field constriction and eventually diminution of the central visual acuity and blindness. The condition has been reported worldwide and its differential diagnosis is broad and includes choroideremia and retinitis pigmentosa. Treatment currently depends on life-long dietary modifications including restriction of the amino acid arginine in diet. This article describes in detail the pathogenesis, clinical features, multimodal imaging findings, and treatment options for GA of the choroid and retina and its complications.

Altered Static and Dynamic Interhemispheric Resting-State Functional Connectivity in Patients With Thyroid-Associated Ophthalmopathy

Purpose: Thyroid-associated ophthalmopathy (TAO) is a debilitating and sight-threatening autoimmune disease that severely impairs patients’ quality of life. Besides the most common ophthalmic manifestations, the emotional and psychiatric disturbances are also usually observed in clinical settings. This study was to investigate the interhemispheric functional connectivity alterations in TAO patients using resting-state functional magnetic resonance imaging (rs-fMRI).Methods: Twenty-eight TAO patients and 22 healthy controls (HCs) underwent rs-fMRI scans. Static and dynamic voxel-mirrored homotopic connectivity (VMHC) values were calculated and compared between the two groups. A linear support vector machine (SVM) classifier was used to examine the performance of static and dynamic VMHC differences in distinguishing TAOs from HCs.Results: Compared with HCs, TAOs showed decreased static VMHC in lingual gyrus (LG)/calcarine (CAL), middle occipital gyrus, postcentral gyrus, superior parietal lobule, inferior parietal lobule, and precuneus. Meanwhile, TAOs demonstrated increased dynamic VMHC in orbitofrontal cortex (OFC). In TAOs, static VMHC in LG/CAL was positively correlated with visual acuity (r = 0.412, P = 0.036), whilst dynamic VMHC in OFC was positively correlated with Hamilton Anxiety Rating Scale (HARS) score (r = 0.397, P = 0.044) and Hamilton Depression Rating Scale (HDRS) score (r = 0.401, P = 0.042). The SVM model showed good performance in distinguishing TAOs from HCs (area under the curve, 0.971; average accuracy, 94%).Conclusion: TAO patients had altered static and dynamic VMHC in the occipital, parietal, and orbitofrontal areas, which could serve as neuroimaging prediction markers of TAO.

Pseudotumor Cerebri in the Setting of Differentiation Syndrome in a Patient with Acute Promyelocytic Leukemia Treated with All-trans Retinoic Acid During Induction Therapy

Introduction: Differentiation syndrome, a well-known complication of all-trans retinoic acid (ATRA) in patients with acute promyelocytic leukemia (APML), can very rarely have ophthalmic manifestations. Pseudotumor cerebri (PC) in the setting of differentiation syndrome (DS) in patients undergoing induction with all-trans retinoic acid has rarely been reported elsewhere. We herein report one such case. Case Presentation: A 28-year-old, non-obese female diagnosed as acute promyelocytic leukemia underwent induction with all- trans retinoic acid and Idarubicin. On day 4 of the treatment, she developed high grade fever (104 – 105 F), dry cough, hypotension, tachycardia, and tinnitus. Chest X ray showed floppy shadows in bilateral lungs. On physical examination, bilateral lower limb edema was noted. She also experienced sudden weight gain of 5 kilogram in 48 hours. After careful exclusion of systemic infection, she was suspected as having DS. She also noticed a reduction in vision in right eye. On eye examination, her best-corrected visual acuity (VA) was 6/60 in the right eye (RE) and 6/6 in the left eye (LE). Fundus evaluation revealed bilateral disc edema with peripapillary hemorrhages along with slight tortuosity of vessels and a yellowish lesion over the fovea in RE. Suspecting DS, she was treated with injection dexamethasone 10 mg twice daily and all- trans retinoic acid was temporarily discontinued. Immediately after its discontinuation, her headache lessened and vision improved gradually. After 2 weeks, her VA was 6/12 in RE and 6/6 in LE which improved to 6/6 in both eyes at 3 months. The patient was also receiving oral voriconazole for fungal prophylaxis and the potentiation effect of all- trans retinoic acid could thus be explained. Conclusion: Pseudotumor cerebri associated with all-trans retinoic acid treatment in acute promyelocytic leukemia, even though frequently reported in pediatric patients, is rare in adults. Ophthalmological evaluation is mandatory in all these patients under all-trans retinoic acid therapy.

Ophthalmic manifestations of herpes virus infection in dogs

This article describes the main aspects of the epizootology and pathogenesis of Cahv-1 (canine herpesvirus), also, the clinical forms of manifestations of pathology in dogs of different ages and physiological status are described. Particular attention is paid to ocular pathologies developing at Cahv-1, such as herpetic conjunctivitis, blepharitis, ulcerative and stromal keratitis. The features of the diagnosis and differentiation of these pathologies are described. The systematic and local medicines used by us in the practice of treating dogs with herpetic eye, the principles and algorithms of their prescription are presented. The difficulties of diagnostics Cahv-1 are described, and the reasons for frequent false-negative results during PCR explained in the article. Besides additional laboratory verification methods for Cahv-1 as well as methods of prevention of herpetic infection of dogs are indicated.

Bilateral neurorethinovasculitis associated with COVID-19 infection in a girl 17 years old

Despite dominant lung lesions, new coronavirus infection (COVID-19) can influence almost any organ, including eyes. According to modern data, frequency of eye damage by COVID-19 reaches 32%, and spectrum of clinical manifestations is diverse. Changes are observed both in the anterior (mainly conjunctivitis) and posterior (mostly retinal vascular thrombosis, optic neuritis, neuroretinitis) segments of the eye, and the timing of their occurrence varies from the first (sometimes the only) clinical symptoms of the disease to the development at the peak or during the period of convalescence from COVID-19. In children symptomatic COVID-19 infection is diagnosed less frequently than in adults, and ophthalmic manifestations are less investigated. This article describes a case of bilateral neuroretinovasculitis in a 17-year-old girl with a mild course of COVID-19, that arose 3 weeks after the onset of the disease, which broadens the understanding of ocular manifestations of COVID-19 in children. We emphasize that an ophthalmologist should know ocular manifestations of COVID-19, which can help in the diagnosis and further study of the frequency and spectrum of ophthalmic symptoms, especially in children