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Biomedical subjects

M A Thiel

Publications and source records attributed to M A Thiel.

At least 19 recordsLinked to original sources

Phosphate concentration in artificial tears.

BACKGROUND: Irrigating solutions and eye drops may contain phosphates as part of their buffer system. In the presence of epithelial keratopathy, a high concentration of phosphate favours corneal calcification. Knowledge of the phosphate concentration in artificial tear products helps to prevent this sight-threatening complication. This study gives an overview on the amount of phosphate contained in artificial tears. METHODS: Fifty-nine samples of commercially available artificial tear preparations were tested. The quantification of phosphate was performed using the molybdate method on a Modular P autoanalyzer. RESULTS: Twenty-six of 59 (44%) artificial tear products had a phosphate concentration above physiological levels (>1.45 mmol/l). A phosphate concentration above 25 mmol/l was found in nine products (15%), a concentration higher than 50 mmol/l in three (5%). CONCLUSIONS: Many artificial tear formulations contain unphysiological levels of phosphate, but very high concentrations are found only in a few products. These preparations have the potential to favour the formation of insoluble crystalline calcium phosphate deposits when used on a damaged corneal surface, and should therefore be used cautiously.

Autoanalysis↗

[Corneal and conjunctival findings in systemic silver intoxication].

BACKGROUND: Chronic silver intoxication is a rare disease and therefore the typical ocular findings may be missed. Based on a case with severe intoxication, the clinical and histological findings as well as the prognosis in argyria are presented. HISTORY: A 33-years-old-employee of a battery production plant developed a biopsy proven systemic argyria. On slit lamp examination the conjunctiva showed a dark, blue-grey discoloration in the areas of the tear flow and the small conjunctival arteries. Diffuse silver deposits were noticed on the level of Descemet's membrane without endothelial damage. Silver deposits were also visible in the trabecular meshwork. Chemical reaction of the silver particles upon exposure to UV light results in irreversible tissue discoloration. Without options for an effective treatment, early diagnosis and prevention of overexposure are most important. CONCLUSIONS: The typical ocular findings in systemic argyria are helpful in occupational medicine for establishing the correct diagnosis.

Adult↗

[Risk of bacterial contamination after povidone-iodine disinfection for cataract surgery].

BACKGROUND: Povidone-iodine alone or in combination with antibiotics is commonly used for presurgical disinfection in cataract surgery. In spite of the use of the combination Povidone-iodine and ofloxacin, the rate of ocular contamination as assessed from surgical knives was reported to be as high as 26 %. The aim of this study was to investigate the efficacy of diluted Povidone-iodine alone for surgical disinfection. PATIENTS AND METHODS: 126 consecutive patients undergoing elective cataract surgery with a conjunctival wound and a scleral tunnel received prior to surgery a disinfection with diluted Povidone-iodine eye drops (Braunol 1:10 diluted = 0.8 % Povidone-iodine, 3 times every 5 min). To assess residual bacteria on the ocular surface after disinfection, the surgical knives for the side ports and the scleral tunnel were cultured in thioglycolate broth. RESULTS: In 8 out of 126 (6 %) patients the culture from the surgical knives revealed a positive result (89 % coagulase negative Staphylococci). Four of these 8 cases occurred during a single list. All control cultures remained negative. CONCLUSION: Diluted Povidone-iodine eye drops alone are highly effective for bacterial disinfection when applied properly. The rate of contamination using 0.8 % Povidone-iodine in our series was considerably lower as compared to that of other studies.

Adult↗

[Povidone-iodine for treatment of adenoviral conjunctivitis: an in vitro study].

BACKGROUND: Adenoviral conjunctivitis causes high socioeconomic costs due to high contagiousness and therefore the need for extended quarantine. To date the only potentially active, topical antiviral agent is povidone-iodine (PVI). The aim of this study was to investigate the effect of diluted PVI on free adenovirus and adenoviral infected cells as well as to evaluate the cellular toxicity of PVI on non-infected cells. MATERIAL AND METHODS: PVI was diluted to a final concentration of 0.0008 %. Virucidal activity was measured IN VITRO using adenovirus 8 and A549 human epithelial cell cultures. Cytotoxicity effects on healthy cells after short- and long-term exposure to diluted PVI were measured in A549 cell cultures. RESULTS: Exposure to PVI at a concentration of 1:10 (0.8 %) completely extinguishes infectivity of free adenovirus after an exposure time of 10 minutes. PVI is less effective against intracellular adenovirus resulting in a decreased infectivity and viral activity for approximately one day with a narrow spectrum between toxicity and virucidal activity. Healthy epithelial cells can be exposed to PVI for up to 6 hours without a cytotoxic effect. CONCLUSIONS: PVI is highly effective against free adenovirus but less effective against intracellular adenoviral particles in already infected cell. Short- and long-term exposure of PVI causes little cytotoxicity for healthy cells. Therefore, administration of diluted PVI at a concentration of 1:10 is a potential option to reduce contagiousness in cases of adenoviral infections.

Adenoviridae↗

Corneal calcification following intensified treatment with sodium hyaluronate artificial tears.

AIM: To report a potential adverse effect of intensified treatment with sodium hyaluronate artificial tears. METHODS: Five cases of deep calcium deposition in the cornea associated with ocular surface disease and frequent use of hyaluronic acid artificial tears are described. All patients used one formulation of phosphate buffered hyaluronate eye drops when rapid calcification developed. All eyes required corneal graft surgery for visual rehabilitation. Specimens at keratoplasty were available for light microscopy and investigation by dispersive x ray analysis. The phosphate concentration in the medication used for topical treatment was measured and compared to alternative hyaluronate preparations. RESULTS: Light microscopy showed dense mineralisation of the entire stroma. The crystalline deposits consisted of hydroxyapatite, Ca5(PO4)3OH. A 50-fold higher concentration of phosphate was measured in the sodium hyaluronate eye drops used for treatment (50.9 mmol/l) when compared with normal serum. The other hyaluronate formulations showed phosphate concentrations from <0.1 mmol/l to 10.9 mmol/l. CONCLUSIONS: The hyaluronate artificial tear formulation "Hylo-Comod" favours the formation of insoluble crystalline calcium phosphate deposits in presence of epithelial keratopathy. This is because of its high phosphate concentration and typically frequent instillation. Manufacturers and prescribers should be aware that topical preparations may contain considerable amounts of phosphate which may lead to sight threatening corneal complications.

Aged↗

Lethal Epstein-Barr virus associated NK/T-cell lymphoma with primary manifestation in the conjunctiva.

BACKGROUND: Lethal midline granulomas (LMG) are very rare angiocentric NK/T-cell lymphomas in association with Epstein-Barr virus. LMG are reported mainly in East Asia occurring in immune compromised patients. HISTORY AND SIGNS: A 41-year old male patient presented with a conjunctival swelling of his upper left eyelid. The lesion had increased over a period of 2 months despite topical corticosteroid treatment. Conjunctival biopsy revealed a highly malignant, CD3 + and BCL2 + extranodal T-cell lymphoma with features of an NK/T-cell origin (CD56 +, TIA + TCR-rearrangement: germline). All lymphoma cells were positive for Epstein-Barr virus RNA. The proliferation rate was highly elevated at 100 %. THERAPY AND OUTCOME: Systemic 1 (st) cycle chemotherapy with cyclophosphamide, doxorubicin, vincristin and prednisone resulted in a complete remission of the swelling within 4 days. However, one week later a massive conjunctival tumour reappeared with only partial regression after combined chemo- and radiotherapy. The patient died within a month because of untreatable pancytopenia due to malignant bone marrow infiltration. CONCLUSIONS: LMG is a rare but highly malignant Epstein-Barr virus associated NK/T-cell lymphoma that can occur in healthy, immune competent Caucasians. This is the first reported case of an LMG in an immune-competent Caucasian patient with primary ocular manifestation. The LMG has a high mortality rate despite systemic treatment and can be lethal within a few months or even weeks.

Antineoplastic Combined Chemotherapy Protocols↗

[Pepper spray injuries of the anterior segment of the eye].

BACKGROUND: A wide variety of pepper sprays is currently available and gaining increasing popularity among both professional guardians and amateurs. Adverse side effects to the anterior segment of the eye are known but underestimated. HISTORY AND SIGNS: We present two cases with severe corneal and conjunctival damage after accidental self injury by a pepper spray (Jet Protector Guardian Angel), benzyl alcohol 90.1 %, capsaicinoids 2.6 %). THERAPY AND OUTCOME: Despite immediate and intensive irrigation, a complete epithelial defect, extensive ischemia to the limbus and the conjunctiva and a circular conjunctival chemosis were diagnosed. After slow re-epithelialization in both cases, a neurotrophic superficial keratitis, a reduced corneal sensibility and in one case deep stromal scarring were noted. CONCLUSIONS: Pepper spray application to the eye might result in severe and permanent damage to the corneo-conjunctival tissue which is not adequately addressed in the current literature. From the present case reports arise the discussion whether the irritative and lipophilic capsacin/benzyl alcohol mixture or the pyrotechnical additives nitrocellulose und sinoxide are responsible for the anterior segment injuries.

Administration, Topical↗

[Loa loa infection of the eye -- a case series].

BACKGROUND: With increasing migration tropical diseases such as Loa loa infections are becoming more frequent in Europe. While the ocular diagnosis is usually straight forward, systemic work-up and treatment requires an interdisciplinary approach. We review the diagnostic and therapeutic work-up of ocular Loa loa infections based on a series of 4 cases that presented between 1998 and 2004. HISTORY AND SIGNS: The first symptoms in all cases were ocular irritations occurring 2 months to 8 years after a trip to West Africa. One case presented with a swollen upper eyelid without a visible worm. In three patients microfilariae were detected in the blood. THERAPY AND OUTCOME: In two cases visible subconjunctival worms could be removed under the slit lamp. Three cases required systemic treatment as inpatients while one case could be observed without systemic treatment. All 4 cases had a favourable outcome with complete eradication of the disease. CONCLUSION: Surgical removal of adult Loa loa worms from the subconjunctival space only improves the ocular symptoms. An interdisciplinary approach (ophthalmology, infectious disease and parasitology) for a systemic work-up and treatment is usually required.

Adolescent↗

Influence of format on in vitro penetration of antibody fragments through porcine cornea.

AIM: Antibody fragments, appropriately formulated, can penetrate through the ocular surface and thus have potential as therapeutic agents. The aim was to investigate the influence of protein fragment format on the kinetics and extent of ocular penetration in vitro. METHODS: Immunoglobulin single chain variable domain fragments of a murine monoclonal antibody with specificity for rat CD4 were engineered with a 20 or 11 amino acid linker by assembly polymerase chain reaction, expressed in Escherichia coli and purified by chromatography. Fab fragments of the parental antibody were prepared by papain digestion. Antibody fragments were formulated with a penetration and a viscosity enhancer and were applied to the surface of perfused pig corneas for up to 10 hours in vitro. Penetration was quantified by flow cytometry on rat thymocytes. RESULTS: 20-mer antibody fragments formed natural monomers and dimers following purification that could be separately isolated, while 11-mer fragments were dimeric. All formats of fragment (20-mer monomers and dimers, 11-mer dimers, Fab) showed penetration through the pig cornea after 6 hours of intermittent topical administration. CONCLUSION: Antibody fragments of different shapes and sizes can penetrate the cornea after topical administration, thereby increasing the potential of this class of proteins for topical ophthalmic use.

Administration, Topical↗

Normalisation of ocular pulse amplitude after embolisation of dural cavernous sinus arteriovenous fistula.

BACKGROUND: The difference in the ocular pulse amplitude between an individual's eyes may reflect abnormalities of the cerebrovascular circulation and has been shown to be helpful in assessing patients with cavernous sinus arteriovenous fistulas. HISTORY AND SIGNS: A 71-year-old woman presented with episcleral injection, proptosis, bruit and retro-orbital pain on the left side. Ocular pulse amplitude as measured by dynamic contour tonometry was 4.38 +/- 1.23 mm Hg in the right and 9.57 +/- 2.71 mm Hg in the left eye. Angiography revealed the haemodynamics of a dural left cavernous sinus arteriovenous fistula. THERAPY AND OUTCOME: Successful occlusion of the fistula was performed by transvenous embolisation. After embolisation, ocular pulse amplitude was 2.84 +/- 0.60 mm Hg in the right and 1.88 +/- 0.29 mm Hg in the left eye. CONCLUSION: In this case of a dural arteriovenous fistula the ocular pulse amplitude as measured by dynamic contour tonometry parallels closely both clinical findings and neuroimaging.

Aged↗

Follicular conjunctivitis caused by a mantle cell lymphoma.

BACKGROUND: Lymphoma of the conjunctiva as part of a systemic disease is rare. The follicular appearance of the lymphocyte hyperplasia may mimic the clinical picture of infectious or allergic conjunctivitis. We report on a case of marked chronic follicular conjunctivitis, finally diagnosed as mantle cell lymphoma. HISTORY AND SIGNS: A 52-year old male with a history of epiphora for one year, presented with follicular conjunctivitis in both eyes, a nodal mass in the upper right eyelid and nuchal lymphadenopathy. No infectious or allergic aetiology could be found. Conjunctival biopsy revealed a mantle cell lymphoma. Magnetic resonance tomography showed a bilateral spread into the orbital cavity. Other sites of involvement were the epipharynx and the cervical, axillary and paratracheal lymph nodes. THERAPY AND OUTCOME: Chemotherapy with hyper-CVAD (cyclophosphamide, vincristine, doxorubicine, dexamethasone) was initiated. After 4 of 6 cycles, all clinical tumour manifestations had disappeared completely. CONCLUSIONS: Conjunctival lymphoma may clinically resemble follicular conjunctivitis. Conjunctival biopsy may lead to early diagnosis and initiation of therapy.

Antineoplastic Combined Chemotherapy Protocols↗

Penetration of engineered antibody fragments into the eye.

Antibodies are powerful immunotherapeutic agents but their use for treating ocular disorders is limited by their poor penetration into the eye. We hypothesized that antibody fragments of relatively small size might penetrate the cornea more readily. Monovalent single chain variable region (scFv) antibody fragments and divalent miniantibodies were engineered from existing monoclonal antibodies, expressed in a bacterial expression system, and purified by metal ion affinity chromatography. Corneoscleral preparations from normal pig and cat eyes were mounted in a corneal perfusion chamber. Intact antibodies and antibody fragments were applied topically to the anterior corneal surface over 12-h periods, and samples were collected from the artificial anterior chamber. Similar experiments were performed with whole enucleated pig and human eyes. Penetration of antibodies and fragments was quantified by high-sensitivity flow cytometry on appropriate target cells. Both monovalent scFv and divalent miniantibody fragments (but not whole immunoglobulin molecules) passed through de-epithelialized and intact corneas after topical administration, and could be detected by antigen binding. Addition of 0.5% sodium caprate facilitated penetration through intact corneas. Topically-applied scFv was found to penetrate into the anterior chamber fluid of rabbit eyes in vivo. The engineered fragments were stable and resistant to ocular proteases. Monovalent and divalent antibody constructs of molecular weight 28 kD and 67 kD, respectively, can penetrate through intact corneas into the anterior chamber, with retention of appropriate antigen-binding activity. Such constructs may form novel therapeutic agents for topical ophthalmic use.

Animals↗

A simple corneal perfusion chamber for drug penetration and toxicity studies.

AIMS: Corneal perfusion chambers are important tools in the development and assessment of ophthalmic drugs. The aim of this study was to design and test a modified perfusion chamber suitable for topical application of drugs to isolated corneoscleral preparations, and which allowed continuous monitoring of endothelial cell function. METHODS: A polycarbonate and stainless steel perfusion chamber was designed to clamp corneas in a horizontal plane suitable for topical drug delivery. Endothelial cell function was assessed by ultrasonic pachymetry and specular microscopy during perfusion. Epithelial barrier function was assessed by penetration of fluorescein. Leakage was examined by measuring penetration of a large protein, IgG. Tissue architecture after perfusion was examined by conventional histology. RESULTS: Corneas maintained a functionally and morphologically intact endothelial monolayer during perfusion periods of up to 14 hours. The epithelial barrier function was well preserved. The tissue clamp sealed the preparation effectively against leakage of macromolecules. CONCLUSION: The new chamber device forms a reliable tool for in vitro drug penetration and toxicity studies in isolated perfused corneoscleral tissue.

Animals↗

[Clinical evaluation of impression cytology in diagnosis of superficial viral infections].

BACKGROUND: Impression cytology is a non invasive technique for the diagnosis of external eye disease. As infected epithelial cells are losing their adhesion to neighbouring cells they are an ideal target for impression cytology. Despite its diagnostic potential impression cytology has not yet become a routine diagnostic tool because of technical inconvenience in use of conventional membranes. The aim of this study was to evaluate a practicable technique of impression cytology for the rapid diagnosis of superficial viral eye disease. MATERIAL AND METHODS: 52 patients with suspected viral conjunctivitis or keratitis underwent impression cytology with a Biopore membrane device. After air fixation immunologic detection tests using either peroxidase antiperoxidase or fluorescent techniques were performed directly on the membrane. RESULTS AND CONCLUSIONS: 21 of 38 patients with suspected Herpes-simplex-virus (HSV), 3 of 4 patients with suspected Varicella-Zoster-virus (VZV) and 2 of 10 patients with suspected Adenovirus infection had a positive result on the impression cytology membrane. These results were confirmed by virus cultures or polymerase chain reactions (PCR) a few days later. No patient with a negative impression cytology had a positive culture result. Using impression cytology and an immunodetection test results became available within 1 to 4 hours. CONCLUSIONS: Impression cytology combined with immunologic detection tests is a rapid, sensitive and practicable diagnostic test for superficial viral eye diseases.

Adenovirus Infections, Human↗

Improved impression cytology techniques for the immunopathological diagnosis of superficial viral infections.

BACKGROUND: For epidemiological and therapeutic reasons early diagnosis of superficial viral infections is crucial. Conventional microbiological techniques are expensive, time consuming, and not sufficiently sensitive. In this study impression cytology techniques were evaluated to analyse their diagnostic potential in viral infections of the ocular surface. METHOD: A Biopore membrane device instead of the original impression cytology technique was used to allow better quality and handling of the specimens. The impressions were processed, using monoclonal antibodies and immunoperoxidase or immunofluorescence techniques to assess the presence of herpes simplex virus, varicella zoster virus, or adenovirus antigens. Ocular surface specimens from healthy individuals (n = 10) and from patients with suspected viral surface disease (n = 19) were studied. Infected and non-infected cell cultures served as controls. RESULTS: This modified technique of impression cytology allowed the collection of large conjunctival and corneal epithelial cell layers with excellent morphology. Immunocytological staining of these samples provided diagnostic results for all three viruses in patients with viral surface disease. CONCLUSIONS: The use of Biopore membrane devices for the collection of ocular surface epithelia offers new diagnostic possibilities for external eye diseases. Immunopathological methods that are applied directly on these membrane devices can provide virological results within 1-4 hours. This contributes considerably to the clinical management of patients with infectious diseases of the ocular surface.

Antigens, Viral↗