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Ocular manifestations of multiple sclerosis.

PURPOSE OF REVIEW: Multiple sclerosis is an autoimmune demyelinating disorder of the nervous system that is commonly manifested by visual system involvement and that may initially present with ophthalmologic symptoms. This paper reviews recent findings regarding the ocular manifestations in multiple sclerosis. RECENT FINDINGS: Manifestations of multiple sclerosis in the eye include both the afferent and efferent visual pathways. Optic neuritis, the most common ocular manifestation of multiple sclerosis, may be the initial clinical disease manifestation. Recent long-term follow-up data show that most patients with demyelinating optic neuritis have an excellent prognosis for recovery of central visual acuity. Evidence is emerging, however, for significant and broad reduction in both contrast sensitivity and color perception in multiple sclerosis patients despite near-normal visual acuities. Ocular motor deficits in multiple sclerosis include internuclear ophthalmoplegia and nystagmus, resulting in diplopia, oscillopsia, blurred visual, loss of stereopsis, and reading fatigue. Multiple sclerosis also may be associated with ocular inflammatory diseases, in particular pars planitis and retinal periphlebitis. SUMMARY: Ocular findings may be initial manifestations of multiple sclerosis and may predict additional demyelinating events. Recognizing these syndromes and signs will help clinicians to properly evaluate the patient, formulate an appropriate differential diagnosis, be able to discuss the prognosis with the patient, and help develop an effective therapeutic plan.

Eye Diseases↗

Cannula thrombophlebitis: a study in volunteers comparing polytetrafluoroethylene, polyurethane, and polyamide-ether-elastomer cannulae.

Cannulae made of polytetrafluoroethylene (PTFE: n = 11), thermoplastic polyether-urethane (TPEU: n = 11), and a new test material, polyamide-ether-elastomer (XLON: n = 10) were inserted into the veins of the dorsum of the hand in 32 healthy volunteers (10 women and 22 men), 21-50 years old. The cannulae were intended to be left in place for 5 days. No infusion was given and the dressings were not exchanged. The resulting thrombophlebitis, defined as two or more of the symptoms pain, redness, oedema and hardness, was estimated on a scale which took into account the incidence, location, intensity, and duration of the symptoms. Except for one volunteer in the XLON group, all the volunteers developed thrombophlebitis, generally observed on the third day of cannulation, and being more frequent and intense over the cannulae (P less than 0.001) and at the tip (P less than 0.01) than at the insertion sites. Pain and oedema were, on the whole, the most frequent and severe symptoms during the period of indwelling. After withdrawal, hardness was the most intense, and together with pain, the most long-lasting (up to 10 days) symptom. The differences between the materials in thrombophlebitis incidence and intensity were statistically significant only when each symptom was analysed separately. Thus, the PTFE cannulae caused more pain and hardness (probably because of greater platelet adhesion and a relatively greater stiffness), while the TPEU and XLON cannulae produced more periphlebitis (redness and oedema), probably because of potentially irritant and antigenic substances leaking from them (polyurethane oligomers and polyamide/polyethyleneglycol oligomers).

Adult↗

Vascular involvement in cutaneous sarcoidosis.

Sarcoidosis is a systemic granulomatous disease with systemic vascular involvement, that is, granulomatous angiitis and microangiopathy. To determine if there is vascular involvement in cutaneous sarcoidosis, we examined 42 skin specimens taken from 32 patients with cutaneous lesions of sarcoidosis. Cutaneous sarcoidosis was prevalent in older females with high serum angiotensin-converting enzyme (ACE) levels. Most skin lesions appeared during the following-up of sarcoidosis. Granulomatous angiitis was present in 12 specimens of sarcoid skin lesions (30.8%). Eight of the 12 specimens showed venous involvement in the dermis. There was no correlation between the incidence of granulomatous angiitis and the gross pattern of cutaneous sarcoidosis. Immunohistochemically, thrombomodulin was negative in the vascular endothelium close to the granuloma or a periphlebitis lesion. Electron microscopy revealed endothelial swelling, luminal narrowing, and basal lamina layering of the basement membrane in the capillaries and venules in the dermis. These findings demonstrated that granulomatous angiitis and microangiopathy coexist in cutaneous sarcoidosis.

Adult↗

Definite multiple sclerosis and uveitis: a two cases report.

Uveitis has infrequently been described as a manifestation of ocular inflammation in patients with multiple sclerosis (MS). Two patients with pre-existing definite MS and uveitis were described. The first patient had features of intermediate uveitis, and the second case had a features of retinal periphlebitis. However, each patient had neurologic signs consistent with MS and a negative laboratory tests for inflammatory and infectious diseases. The presence of neurological involvement with uveitis need a sequential diagnostic search.

Adult↗

Changes in the retinal veins in acute optic neuritis.

OBJECTIVE: To investigate patients with acute optic neuritis (ON) for changes of the retinal veins. MATERIAL AND METHODS: Seventy-six patients with acute ON were extensively neuro-ophthalmologically examined. RESULTS: Multiple sclerosis (MS) was found in 41 patients of whom 1 had periphlebitis retinae (PR) and 2 had venous sheathing (VS). Probable MS was found in 15 patients without prior symptoms of MS. One had PR and VS, and 2 had VS. Twenty patients had mono-symptomatic ON, none had retinal changes. CONCLUSION: Changes of the retinal veins should alert the clinician to a probable diagnosis of MS. ON appears frequently as the initial symptom of MS. Our observation of VS in these patients suggest that clinically silent retinal disease activity had occurred prior to the ON.

Acute Disease↗

Course and complications of intermediate uveitis.

Intermediate uveitis is associated with a wide variety of complications, particularly in patients attending uveitis referral centres, but little information exists on the frequency of these complications in a general pool of patients. We reviewed all the cases known to have originated in one English county. 86 eyes of 48 patients with a mean follow-up of 48 months were affected. The principal threat to sight was cystoid macular oedema (31%). Other complications included vitreous haemorrhage (8%), disc swelling (5%), periphlebitis (21%) and cataract (5%). Most patients required no treatment other than observation and overall the visual outcome was good with 85% of patients and 63% of eyes having vision of 6/9 or better. Cystoid macular oedema and snowbanking were significantly associated with a worse visual outcome, whilst the other complications were not.

Adolescent↗

Ocular manifestations of Behçet's disease.

The manifestations, possible etiological factors and therapeutical modalities of ocular Behçet are outlined. The major ocular findings involve both the anterior and posterior uvea. The vasculitis retinae, the periphlebitis and the pipe stem sheathing along with the recurrent vitreous hemorrhages lead to the visual impairment. Exacerbation and remission of the ocular inflammatory processes are characteristic. However, the impairment of visual function occurring after each attack is generally irreversible. The effectiveness of the present modalities of treatment is uncertain. Chlorambucil in doses of 6-8 mg daily appears to have an outstanding beneficial effect. However, carefully monitored control studies are lacking and should be conducted before any unequivocal conclusions can be reached. It appears to us that the etiology-pathology of Behçet's disease might be a sequence of events triggered by an interaction between a virus and specific receptors on the host cell membrane (HLA determined?). This initial interaction is followed by a malregulation of the host immune mechanism leading to autoimmune phenomena which are characteristics of the disease.

Behcet Syndrome↗

Systematic pathogenesis and replication of avian hepatitis E virus in specific-pathogen-free adult chickens.

Hepatitis E virus (HEV) is an important human pathogen. Due to the lack of a cell culture system and a practical animal model for HEV, little is known about its pathogenesis and replication. The discovery of a strain of HEV in chickens, designated avian HEV, prompted us to evaluate chickens as a model for the study of HEV. Eighty-five 60-week-old specific-pathogen-free chickens were randomly divided into three groups. Group 1 chickens (n=28) were each inoculated with 5 x 10(4.5) 50% chicken infectious doses of avian HEV by the oronasal route, group 2 chickens (n=29) were each inoculated with the same dose by the intravenous (i.v.) route, and group 3 chickens (n=28) were not inoculated and were used as controls. Two chickens from each group were necropsied at 1, 3, 5, 7, 10, 13, 16, 20, 24, 28, 35, and 42 days postinoculation (dpi), and the remaining chickens were necropsied at 56 dpi. Serum, fecal, and various tissue samples, including liver and spleen samples, were collected at each necropsy for pathological and virological testing. By 21 dpi, all oronasally and i.v. inoculated chickens had seroconverted. Fecal virus shedding was detected variably from 1 to 20 dpi for the i.v. group and from 10 to 56 dpi for the oronasal group. Avian HEV RNA was detected in serum, bile, and liver samples from both i.v. and oronasally inoculated chickens. Gross liver lesions, characterized by subcapsular hemorrhages or enlargement of the right intermediate lobe, were observed in 7 of 28 oronasally and 7 of 29 i.v. inoculated chickens. Microscopic liver lesions were mainly lymphocytic periphlebitis and phlebitis. The lesion scores were higher for oronasal (P=0.0008) and i.v. (P=0.0029) group birds than for control birds. Slight elevations of the plasma liver enzyme lactate dehydrogenase were observed in infected chickens. The results indicated that chickens are a useful model for studying HEV replication and pathogenesis. This is the first report of HEV transmission via its natural route in a homologous animal model.

Animals↗

Neuro-ophthalmic sarcoidosis.

Sarcoidosis is a multisystem disorder in which ocular involvement occurs in about one-quarter and neurosarcoidosis in 7 per cent of patients. When the retina is involved, the reported incidence of central nervous system sarcoidosis is 37 per cent. The patient described had a transient papular eruption of the legs, bilateral hilar lymphadenopathy, polyarthralgia with knee effusions, and bilateral facial and peripheral neuropathy. Ocular involvement was characterized by anterior uveitis (in the initial stages), vitreous flare, bilateral disc oedema, macular oedema, streak haemorrhages, peripheral periphlebitis, nerve fibre bundle defects, and candle-wax spots. Fluorescein angiography showed no fluorescence of the candle-wax spots nor of the adjacent vessels. However, there was hyperfluorescence of two retinal lesions. This patient had unilateral internal ophthalmoplegia, only three cases of which have been reported in the literature. Her health was restored by heavy, prolonged corticosteroid therapy. Her family history revealed that an uncle died of sarcoidosis complicated by cryptococcal meningitis. The literature on retinopathy in sarcoidosis is reviewed and the lesions noted in the posterior segment are listed.

Adult↗

Experimental posterior uveitis. I: A clinical, angiographic, and pathological study.

The clinical, angiographic, and histopathological features of experimental posterior uveitis in the black hooded Lister rat are described. This mild form of experimental allergic uveoretinitis (EAU) is induced by sensitisation with retinal S antigen in Freund's complete adjuvant, and the inflammation produced is confined to the posterior segment of the eye. This allows for the first time precise photographic and angiographic documentation of the evolution of clinical signs, because there is minimal clouding of the vitreous by inflammatory cells. Clinically the disease is characterised by the appearance of disc oedema and periphlebitis, followed by focal infiltrates in the deep retinal layers, with eventual atrophy of the pigment epithelium. Histologically, retinal vasculitis is associated with focal mononuclear cell infiltration and necrosis of the photoreceptor layers. This model closely resembles the clinical features of idiopathic retinal vasculitis seen in man.

Animals↗

Fuchs' heterochromic uveitis and sarcoidosis.

AIMS/BACKGROUND: The aetiology of Fuchs' heterochromic uveitis (FHU) is unknown although it can occur in combination with a number of different ocular conditions. Five patients with FHU who show an association with sarcoidosis were studied. METHODS: Four patients with clinical signs compatible with FHU who had elevated serum angiotensin converting enzyme levels (sACE), and a fifth case with a normal sACE and a positive Kveim test were described. RESULTS: All five cases had iris nodules, two later developed mutton fat keratic precipitates, and one had peripheral retinal periphlebitis. Of the four cases with elevated sACE, one had respiratory function test abnormalities and an abnormal chest x ray compatible with pulmonary sarcoidosis. Another had a chorioretinal scar and developed intermediate uveitis 2 years after presentation. CONCLUSIONS: In all of these cases a diagnosis of FHU may represent a specific secondary ocular response to sarcoidosis rather than a primary idiopathic uveitis syndrome. Although FHU remains a clinical diagnosis, routine uveitis investigations should still be performed in this group of patients.

Adolescent↗

Serum homocysteine level is increased and correlated with endothelin-1 and nitric oxide in Behçet's disease.

BACKGROUND/AIMS: Behçet's disease (BD) is a systemic inflammatory vasculitis of young adults with unknown aetiology, characterised by endothelial dysfunction and occlusion in both deep venous and retinal circulation. Ocular involvement occurs in 70% of cases and is characterised by periphlebitis, periarteritis, vascular occlusion, and thrombosis leading to blindness despite vigorous treatment. Endothelin-1 (ET-1) is a vasoconstricting peptide while nitric oxide (NO) is a relaxing molecule and both are released by endothelium for blood flow regulation. Homocysteinaemia is a newly defined term connected to the increased risk of atherothrombotic and atherosclerotic systemic and retinal vascular occlusive diseases, and its role in the course of BD has not been previously described. The authors aimed to detect serum total homocysteine (tHcy), ET-1, and NO in BD and to assess if tHcy, ET-1, and NO are associated with ocular BD or disease activity. METHODS: 43 consecutive patients with ocular (n = 27) or non-ocular (n = 16) BD (36.95 (SD 9.80) years, 22 male, 21 female) satisfying international criteria, and 25 age and sex matched healthy control subjects (37.88 (8.73) years, 13 male, 12 female) without a history of systemic or retinal venous thrombosis were included in this study. Patients were examined by two ophthalmologists with an interest in BD. Serum tHcy, ET-1, and NO concentrations were measured in both groups. Hyperhomocysteinaemia was defined as a tHcy level above the 95th percentile in the control group. Patients were divided into active and inactive period by acute phase reactants including alpha(1) antitrypsin, alpha(2) macroglobulin, erythrocyte sedimentation rate, and neutrophil count. RESULTS: The overall mean serum tHcy, ET-1, and NO levels were significantly higher in patients with BD than in control subjects (tHcy = 15.83 (4.44) v 7.96 (2.66) ng/ml, p <0.001; ET-1 = 17.47 (4.33) v 5.74 (2.34) micromol/ml, p <0.001; NO = 37.60 (10.31) v 27.08 (7.76) micromol/l, p <0.001). Serum tHcy, ET-1, and NO levels were significantly higher in active patients than in inactive patients and control subjects. In addition, among patients with ocular BD, the mean tHcy levels were significantly increased and correlated with ET-1 and NO levels when compared with non-ocular disease and control subjects. All acute phase reactant levels were significantly higher in active period than in inactive stage and controls. CONCLUSIONS: Elevated tHcy may be responsible for the endothelial damage in BD and may be an additional risk factor for the development of retinal vascular occlusive disease, contributing to the poor visual outcome in these patients. Assessment of tHcy may be important in the investigation and management of patients with BD, especially with ocular disease.

Acute-Phase Proteins↗

Retinal vasculitis.

Evidence is now accumulating on both clinical and experimental grounds that the retina is an a priori source of inflammatory activity. Reactive inflammation in the retina may produce many of the clinical signs previously ascribed to uveal inflammation. Autoimmune mechanisms are probably responsible for the majority of cases of retinal vasculitis. Autoimmune retinal vasculitis occurs without other classical signs of inflammatory response in any other parts of the body. When associated systemic manifestations occur they may reflect different underlying immunopathogenic abnormalities. Thus in diseases with predominantly arterial involvement (e.g. systemic lupus erythematosus, polyarteritis nodosa) the retinal arteries bear the brunt of this disease. In Behçet's disease the systemic involvement is usually venous and ocular involvement produces diffuse capillary and venous inflammation with areas of retinal necrosis and major vascular occlusion. The retinal appearances differ from sarcoidosis in which a granulomatous response produces characteristic periphlebitis. Finally, autoimmune retinal vasculitis produces diffuse capillary and venous damage, without any systemic signs. In the next decade the search will be for the identification of the specific antigens initiating these disparate retinal features. Retinal S antigen is a potent antigen, but rhodopsin, interphotoreceptor binding protein, and transducin all need further experimental investigation. Precise documentation will herald the dawn of new therapeutic measures based on a sound immunological fabric.

Adult↗

Glioblastoma associated with multiple sclerosis: coincidence or induction?

A 63-year-old man died of a brain tumor 29 years after onset of multiple sclerosis (MS). The MS diagnosis was based upon clinical evidence of two brain stem lesions, separate in time, retinal periphlebitis, a fluctuating course of the disease, and supported by the observation of definite cognitive impairment at the age of 41 years, and an increased number of lymphocytes in the cerebrospinal fluid which normalized during gradual recovery. The MS diagnosis was confirmed at autopsy, which also revealed a glioblastoma developing adjacent to typical MS plaques.

Brain↗

Ophthalmic manifestations of acquired immunodeficiency syndrome. A study of thirty-four patients.

Ophthalmic manifestations were studied in 34 patients suffering from AIDS. Ophthalmic disorders were found in 20 of these (58%), the most frequent being a cotton-wool-type spot (94.7%). Three patients showed an ophthalmic state compatible with choroid ischemia and atrophy of the pigmented epithelium of the retina. Three patients had necrotizing retinitis probably of viral etiology (cytomegalovirus). Other disorders observed were intraretinal hemorrhages, Roth's spots, microaneurysms, periphlebitis and ocular infiltration by Kaposi's sarcoma.

Acquired Immunodeficiency Syndrome↗

Drug injection in jugular veins: a new risk factor for vascular diseases in HIV-infected patients? A case report.

The authors describe a rare case of diffused thrombosis of the superficial veins in the whole body and periphlebitis with perivascular abscesses in an human immunodeficiency virus (HIV)-infected drug abuser who was using neck veins to inject cocaine and heroin. In addition the patient presented oral candidiasis, hepatitis C virus infection, bronchopneumonitis, and endocarditis of the tricuspid valve with valvular failure. The conditions of the patient needed repeated vascular catheterizations for therapy administration. Similar pathologies, in HIV-infected patients, highly increase the risk of opportunistic infections, especially in the encephalic territory; in addition the need for vascular catheterizations represents a further risk factor for bacterial infections.

Abscess↗

Histopathology of herpes simplex virus keratouveitis.

Twenty-four eyes removed for complications of HSV keratitis were studied histopathologically. There were 20 men and 4 women with an average age of 61 years. Severe keratitis was seen in 14, moderate in 7, and mild in 3 eyes. Common features associated with severe keratitis were: acute perforation, granulomatous keratitis with giant cells in the stroma and Descemet's region, stromal inflammatory cells, angle-closure, severe iridocyclitis with diffuse or focal infiltration of lymphocytes and plasma cells, low-grade vitritis, choroiditis, and/or retinal periphlebitis. Specimens with moderate to mild keratitis had a similar distribution of inflammation but a lower incidence of granulomatous keratitis.

Adult↗

Familial pars planitis.

Pars planitis is an intraocular inflammatory disorder which usually affects children or young adults and is characterized by vitreous cells and debris ('snowballs'), exudate, and 'snowbank' formation along the pars plana, variable periphlebitis, and cystoid macular edema. Although no inheritance pattern has been defined, familial cases of pars planitis have been reported. This report describes pars planitis in two sisters, one of whom had evidence of demyelinating disease at presentation. The literature on familial pars planitis is reviewed. To the author's knowledge this is the first case of familial pars planitis as the presenting sign of possible demyelinating disease.

Administration, Oral↗