Central Retinal Artery Occlusion in Rhino-Orbital-Cerebral Mucormycosis: An Inflammatory-Prothrombotic State.

PURPOSE: The aim was to evaluate patient profiles of rhino-orbital-cerebral mucormycosis (ROCM) cases with central retinal artery occlusion (CRAO) postcoronavirus disease 2019. DESIGN: A nonrandomized retrospective case-control study. METHODS: The ROCM cases presenting with CRAO were compared with a control ROCM group without CRAO at a tertiary care center. Demography, systemic status, clinical features, histopathology, imaging, and blood profile were assessed for any specific risk factors. RESULTS: A total of 12 patients were seen in the CRAO group and 16 in the non-CRAO group. The male-to-female ratio was 3:1 with a mean age of 49.5 years. In the CRAO group, 75% had diabetes mellitus with mean hemoglobin A1c of 9.03%, and 66.7% had received steroid treatment. All cases were histopathologically confirmed positive for mucor. There was a significant difference in mean D-dimer and serum ferritin between the 2 groups, with higher level in the CRAO group. All patients with CRAO had light perception-negative vision, with total ophthalmoplegia and proptosis seen in 66.7% of cases. Four patients had orbital apex involvement, 5 had cavernous sinus involvement, and 8 had intracranial involvement in the CRAO group. CONCLUSIONS: Inflammatory markers D-dimer and serum ferritin were significantly associated with CRAO, suggestive of hyperinflammatory and hypercoagulable state. A high index of suspicion should be maintained in cases with elevated markers and prophylactic anticoagulants can be started to prevent CRAO in a subset of patients.

ANCA-Negative Churg-Strauss Syndrome Presenting as Bilateral Central Retinal Artery Occlusion: A Case Report

A 42-year-old man with undiagnosed Churg-Strauss syndrome (CSS) developed bilateral central retinal artery occlusion (CRAO). His medical history included bronchial asthma and irregular prednisolone usage but no atherosclerotic risk factors. At presentation, visual acuity (VA) was hand motion in the right eye and counting fingers in left eye. On fundoscopy, retinal whitening and a cherry red spot were observed in the right eye, while the fundus was normal in the left eye. After eyeball massage and systemic intraocular pressure lowering agents, his VA improved. On day 5 of treatment, he experienced right limb weakness and purpura on his right foot, and electromyography revealed mononeuritis multiplex. Laboratory tests indicated eosinophilia (52%). Based on the presence of hypereosinophilia, bronchial asthma, mononeuritis multiplex, vasculitis purpura, and sinusitis that was detected during etiological investigations, the patient was diagnosed as having CSS according to the American College of Rheumatology diagnostic criteria. Intravenous methylprednisolone 1 g/day was administrated for 3 consecutive days and 1 g cyclophosphamide was started and continued monthly for 6 months. Foot drop and vasculitic purpura improved after 7 days, but there was no further improvement in visual acuity. In conclusion, in the presence of bilateral CRAO and lack of atherosclerotic risk factors, CSS should be considered as a predisposing factor and investigations should be conducted accordingly.

Diagnostic Dilemma in Sequential Branch Retinal Vein and Artery Occlusion.

PURPOSE: To report on an unusual case of a branch retinal vein occlusion followed by occlusion of the respective branch retinal artery of the same eye 7 years later, in a young, otherwise healthy man with marginal elevation of antiphospholipid antibodies. CASE REPORT: On first presentation, a 30-year-old male patient was diagnosed as having a branch retinal vein occlusion with the sole risk factor of slightly increased diastolic pressure. On second presentation, 7 years later, a transient occlusion of the respective branch retinal artery was diagnosed on the same patient. Extensive ophthalmologic and general medical evaluations were performed including cardiovascular, coagulation, and immunology testing. Coagulopathy screening revealed slightly elevated titers of anticardiolipin IgM and anti-beta 2 glycoprotein-I IgM antibodies, and aspirin prophylaxis was initiated. CONCLUSIONS: Retinal vascular occlusions are typically associated with well-defined, classical risk factors in older people. In younger, otherwise healthy patients, further autoimmune hypercoagulable disorders are often causal. Our case suggests the contribution of slightly elevated antiphospholipid IgM antibodies, although this remains to be proven.

[Susac syndrome: an interdisciplinary challenge]. / Susac-Syndrom : Eine interdisziplinäre Herausforderung.

Susac syndrome, named after John Susac, the first to describe this condition, is characterized by the clinical triad of encephalopathy, branch retinal artery occlusion, and sensorineural hearing loss. Although certainly a rare disease, Susac syndrome needs to be considered in the differential diagnosis of a broad variety of diseases. The pathogenesis is not yet clear. Autoimmune processes leading to damage and inflammation-related occlusion of the microvessels in brain, retina, and inner ear are thought to play a causal role. The diagnosis is based primarily on the clinical presentation, the documentation of branch retinal artery occlusion by fluorescence angiography, and characteristic findings on cerebral MRI. Usually, immunosuppressive therapy is required, though controlled therapy trials are missing so far. The intention of this review article is to raise awareness of this disease among neurologists, psychiatrists, ophthalmologists, and ENT specialists as a high number of unreported cases probably exists. Accordingly, the focus is on the clinical presentation and the diagnostic approach.

Susac's syndrome: 1975-2005 microangiopathy/autoimmune endotheliopathy.

Susac's syndrome (SS) consists of the clinical triad of encephalopathy, branch retinal artery occlusions (BRAO) and hearing loss. It is due to a microangiopathy affecting the precapillary arterioles of the brain, retina, and inner ear (cochlea and semicircular canals). Women are more commonly affected than men (3:1); the age of onset ranges from 9 to 58 years; but young women between the ages of 20 and 40 are most vulnerable. The encephalopathy is almost always accompanied by headache which may be the presenting feature. Multifocal neurological signs and symptoms, psychiatric disturbances, cognitive changes, memory loss, and confusion may rapidly progress to dementia. The MRI shows a distinctive white matter disturbance that always affects the corpus callosum. The central callosal fibers are particularly vulnerable and central callosal holes develop as the active lesions resolve. Linear defects (spokes) and rather large round lesions (snowballs) sometime dominate the MRI findings, which include cortical, deep gray (70%) and leptomeningeal involvement (33%). Frequently, the lesions enhance and may be evident on diffusion weighted imaging (DWI). The BRAO are best evaluated with fluorescein angiography, which may show the pathognomonic multifocal fluorescence. Gass plaques are frequently present and reflect endothelial damage. Brain biopsy shows microinfarction to be the basic pathology, but more recent pathological studies have shown endothelial changes that are typical for an antiendothelial cell injury syndrome. Elevated levels of Factor VIII and von Willebrand Factor Antigen reflect the endothelial perturbation. Despite extensive evaluations, a procoagulant state has never been demonstrated. SS is an autoimmune endotheliopathy that requires treatment with immunosuppressants: steroids, cyclophosphamide, and intravenous immunoglobulin, usually in combination. Aspirin is a useful adjunct.

Treatment of Susac's syndrome.

Susac's syndrome (SS) is an immune-mediated endotheliopathy that affects the microvasculature of the brain, retina, and inner ear. SS responds well to immunosuppressive therapies when treatment is prompt, aggressive, and sustained. Striking similarities exist between SS and dermatomyositis (DM), regarding immunopathogenesis, natural history, and treatment needs. We apply lessons learned from study of DM to SS, and offer our current treatment protocol for SS. Since these treatment guidelines are based mainly on anecdotal evidence, they represent only preliminary recommendations.

Antiphospholipid antibodies in ocular arterial and venous occlusive disease.

PURPOSE: It was the aim of this study to evaluate antiphospholipid antibodies (APA), i.e. lupus anticoagulants (LA) and anticardiolipin (ACA) IgG and IgM, in ophthalmic occlusive disease. METHODS: Over a 3.5-year period, APA were evaluated in 368 patients. RESULTS: Eighty-six patients (23.4%), compared to 5% in the general population, tested positive for APA. APA did not differ significantly between patients with venous (20.6%) or arterial (25.5%) occlusive disease. This included 93 patients with central retinal vein occlusion (18% APA positive), 67 with retinal branch vein occlusion (24% APA positive), 41 with central retinal artery occlusion (22% APA positive), 53 with retinal branch artery occlusion (32% APA positive), 71 with anterior ischemic optic neuropathy (23% APA positive), 12 with posterior ischemic optic neuropathy (33% APA positive) and 31 patients with amaurosis fugax (23% APA positive). Excluding patients with accepted main risk factors, APA were positive in 15.3% of 85 patients. CONCLUSION: The high APA prevalence confirms its relevance in ocular occlusive disorders.

Chlamydia pneumoniae in central retinal artery occlusion.

PURPOSE: There is increasing evidence that the common respiratory human pathogen Chlamydia pneumoniae has a causative role in atherosclerosis. We investigated the association of this pathogen with acute central retinal artery occlusion (CRAO). PATIENTS AND METHODS: Sera of 14 consecutive patients with CRAO and of 14 age- and sex-matched control subjects were examined. Antibodies against chlamydial lipopolysaccharide (LPS) and outer membrane proteins of C. pneumoniae were determined by an enzyme-linked immunosorbent assay (ELISA). RESULTS: In the CRAO group, seven patients (50%) were found to be IgA positive, 12 (86%) were IgG positive and one (7%) was IgM positive for chlamydial LPS antibodies. In the control group 36%, 79% and 14% were IgA, IgG and IgM positive, respectively. The results showed no significant difference between the groups. In the CRAO group, IgA, IgG and IgM antibodies to C. pneumoniae were found in 43%, 79% and 0% of subjects, respectively. These findings did not differ significantly from those pertaining to matched controls. CONCLUSIONS: These data do not support an association between acute CRAO and current C. pneumoniae infection.

Recurrent arterial thrombosis in a child: primary antiphospholipid antibody syndrome.

Antiphospholipid antibody syndrome (APS) is characterized by the association of recurrent arterial or venous thrombosis or recurrent fetal wastage and the presence of circulating antiphospholipid antibodies, detected as anticardiolipin antibodies or lupus anticoagulant. The authors report an 8-year-old girl, who presented with central retinal artery occlusion and live do reticularis and was diagnosed as APS. Despite the proper anticoagulant treatment she had several cerebral ischemic events and died 29 months after the diagnosis. A larger number of pediatric case investigations will be required for better understanding and treating this rare thrombotic disorder.

Antiphospholipid antibodies: a risk factor for occlusive retinal vascular disorders. Comparison with ocular inflammatory diseases.

OBJECTIVE: To evaluate the prevalence of antiphospholipid antibodies (aPL) together with immunological characteristics of patients with occlusive retinal vascular disorders (ORVD) with and without risk factors (systemic arterial hypertension, diabetes mellitus, hyperlipidemia, and embolizing cardiac disease) for retinal occlusions compared to patients with ocular inflammatory diseases (OID) and healthy controls. METHODS: Sixty-eight patients with ORVD, 45 patients with OID, and 49 healthy persons were prospectively studied. Serologic studies included determination of anticardiolipin antibodies, lupus anticoagulant, antinuclear antibodies (ANA), levels of complement 4 and 3, total hemolytic complement (CH100), and circulating immune complexes (CIC). RESULTS: Elevated levels of aPL were detected in 16 (24%) patients with ORVD compared to 4 (9%) patients with OID (OR 3.15, p < 0.05) and 4 (8%) controls (OR 3.46, p < 0.05). No significant differences were seen in the prevalence of aPL comparing risk factor-positive patients with ORVD (8 of 33, 24%) to risk factor-free patients with ORVD (8 of 35, 23%). A higher frequency of positive ANA, elevated IgA, and increased CIC were detected in aPL positive patients with ORVD compared to patients with OID. CONCLUSION: Detection of aPL in patients with ORVD may help determine which patients are eligible for prophylactic treatment. An immunologic profile characterized by high prevalence of ANA, CIC, and elevated IgA distinguishes ORVD patients with aPL from inflammatory ophthalmologic disorders.

Antiphospholipid antibodies and retinal thrombosis in patients without risk factors: a prospective case-control study.

PURPOSE: To determine the prevalence of antiphospholipid antibodies and other immunologic abnormalities in patients with occlusive retinal vascular events, exempt from conventional risk factors of retinal thrombosis. METHODS: Forty patients with retinal vascular occlusion (26 with retinal vein occlusions, eight with arterial occlusions, two with combined venous and arterial occlusions, and four with venous occlusions plus vasculitis), free of main accepted risk factors for retinal thrombosis, were prospectively screened for antiphospholipid antibodies (anticardiolipin-antibodies and lupus anticoagulant) and other immunologic abnormalities. Fourteen patients were younger than 50 years. Prevalence and mean values of antiphospholipid antibodies (aPL) were compared with those in a homogeneous control group of 40 patients. RESULTS: The prevalence of antiphospholipid antibodies in the study group was 22.5% (nine of 40). Comparison with control group prevalence (5% [two of 40]) showed a statistically significant difference (P = .04). Six patients in the study group disclosed positivity for IgG-anticardiolipin antibodies, one patient for IgM anticardiolipin antibodies, and two patients for both isotypes IgG and IgM anticardiolipin antibodies. The antibody assay for lupus anticoagulant was negative for all patients. Three patients were diagnosed as having primary antiphospholipid antibody syndrome and are undergoing systemic anticoagulant therapy. Relevant immunologic abnormalities were also found (27.5% with antinuclear antibodies, 35% with elevation of circulating immune complexes, 35% with complement deficiency, 30% with positive rheumatoid factor, and 17.5% with positive C-reactive protein). Thirteen patients (32.5%) had more than four parameters altered. No significant association was found between prevalence or mean values of anticardiolipin antibody and patients younger than 50 years. CONCLUSIONS: The high prevalence of anticardiolipin antibodies in patients with vaso-occlusive retinopathy exempt from conventional risk factors, and the relevant diagnostic and therapeutic implications, lead us to recommend a systematic search for specific antiphospholipid antibodies in such patients.

Retinopatia vascular associada à Síndrome Antifosfolípide / Vascular occlusive retinopathy associated with anti-phospholipid antibodies

Os autores descrevem 2 casos (4 olhos) de retinopatia vaso-oclusiva periférica severa associada à síndrome antifosfolípide e descrevem também a fisiopatologia e alternativas terapêuticas desta condiçäo especial

Ocular involvement in primary antiphospholipid syndrome. Ocular involvement in primary APS.

UNLABELLED: The purpose of this study is to evaluate the ocular findings in patients with the primary antiphospholipid syndrome (APS). PATIENTS AND METHODS: Twenty-two patients (44 eyes) with primary APS (17 women, 5 men) were examined. All patients were younger than 50 years (median age; 37.5 years). In 18 patients, fundus flourescein angiography was performed in addition to the ophthalmologic examination. RESULTS: Sixteen patients (72.7%) described visual symptoms. Anterior segment was normal in 19 patients (86.4%). Posterior segment abnormalities were observed in 15 patients (68.2%). Venous dilatation and tortuosity were the most common ocular findings. Retinal vascular occlusive disease was detected in 5 patients (22.7%). Flourescein angiography abnormalities were noted in 14 of the 18 patients (77.8%). The most common angiographic finding was pigment epithelial window defects. CONCLUSIONS: Our results indicate that posterior eye segment involvement is relatively common in the primary APS. It also seems that the screening for APS is important in young patients with retinal vascular occlusion, especially in those without conventional risk factors.

Anticardiolipin antibodies and occlusive vascular disease of the eye: prospective study.

There is a recognized association between the presence of anticardiolipin antibodies and vascular occlusive disease. The purpose of our study is to detect the presence of high titers of anticardiolipin antibodies (ACA) in the serum and to correlate the titers with the severity of the vascular disease in patients with occlusive ocular vascular disease. 82 patients were included in a prospective study; 25 patients with anterior ischaemic optic neuropathy, 36 with retinal vein occlusion and 21 with retinal artery occlusion. ACA (IgG and IgM isotypes) were measured by ELISA in the sera of all patients. The group of the patients (group A) was compared to an age-matched control group of 79 healthy individuals (group B). IgG isotype (but not IgM) titers of ACA were found significantly higher in group A (P < 0.001). In patients with titers of ACA (IgG isotype) > 100 units we noted a higher incidence of a more severe disease (recurrency, involvement of both eyes or extraocular manifestations) especially among those with anterior ischaemic optic neuropathy and secondarily in those with retinal artery occlusion. Our results suggest that the association between high titers of ACA and occlusive vascular disease of the eye concerns only the IgG isotype. In addition, the detection of high titers of IgG/AGA in patients could be a useful marker for disease severity and prognosis and this observation seems to be more explicit in cases with arterial occlusive disease than in cases with venous occlusive disease.