[Primary intrastromal iris cysts]. / Primäre stromale Iriszysten.

BACKGROUND: Cysts of the iris are uncommon and most of them occur secondarily after surgery or penetrating injury. The minority of the iris cysts is primary without a reasonable cause. They are classified into the more common pigment epithelial cysts and the rare cysts of iris stroma ("intrastromal cysts"). These intrastromal iris cysts are generally diagnosed in children and often cause symptoms such as a decrease of visual acuity because of ingrowth into the optical axis. A diagnosis of stromal cysts in adults is very rare. Most of these patients remain without any symptoms and do not need treatment. The cellular origin is so far unknown. Mesoderm, neuroectoderm and surface ectoderm have been discussed in this context. CASE REPORTS: Two patients with primary intrastromal iris cysts are presented, a 5-year-old boy and a 65-year-old woman. In both cases, the cyst affected the optical axis and was removed by sector iridectomy. In histological and electron-microscopic examinations both cysts presented a typical epithelial structure. Immunohistochemical examination revealed positivity for epithelial markers and negativity for mesenchymal and neuroectodermal markers. CONCLUSION: Primary intrastromal iris cysts can occur in advanced age and may cause symptoms due to progressive growth. The cellular origin of primary intrastromal iris cysts is controversially discussed in the literature. On electron microscopy and immunohistochemistry, the iris cysts presented here showed characteristic features of surface ectodermal origin.

TGFBI (BIGH3) gene mutations in German families: two novel mutations associated with unique clinical and histopathological findings.

BACKGROUND: To report the clinical, histopathological and immunohistochemical findings of two novel mutations within the TGFBI gene. METHODS: The genotype of 41 affected members of 16 families and nine sporadic cases was investigated by direct sequencing of the TGFBI gene. Clinical, histological and immunohistochemical characteristics of corneal opacification were reported and compared with the coding region changes in the TGFBI gene. RESULTS: A novel mutation Leu509Pro was detected in one family with a geographic pattern-like clinical phenotype. Histopathologically we found amyloid together with non-amyloid deposits and immunohistochemical staining of Keratoepithelin (KE) KE2 and KE15 antibodies. In two families and one sporadic case the novel mutation Gly623Arg with a late-onset, map-like corneal dystrophy was identified. Here amyloid and immunohistochemical staining of only KE2 antibodies occurred. Further, five already known mutations are reported: Arg124Cys Arg555Trp Arg124His His626Arg, Ala546Asp in 13 families and five sporadic cases of German origin. The underlying gene defect within the TBFBI gene was not identified in any of the four probands with Thiel-Behnke corneal dystrophy. CONCLUSIONS: The two novel mutations within the TGFBI gene add another two phenotypes with atypical immunohistochemical and histopathological features to those so far reported.

[N-acetylcysteine improves lysosomal function and enhances the degradation of photoreceptor outer segments in cultured RPE cells]. / N-Acetylcystein verbessert die lysosomale Funktion und beschleunigt den Abbau von Photorezeptoraussensegmenten in der RPE-Zellkultur.

BACKGROUND: In the retinal pigment epithelium (RPE) lipofuscin granules accumulate with age in the lysosomal compartment mainly as a byproduct of constant phagocytosis of oxidized membranous discs shed from photoreceptor outer segments. Antioxidative defiency and prooxidative conditions in the RPE play a key role in the pathogenesis of RPE dysfunction and macular degenerations such as ARMD. In human RPE cell cultures we investigated the antioxidative effect of N-acetylcysteine (ACC) on lysosomal functions. METHODS: Primary human RPE cell cultures were loaded with regular or oxidized human and porcine rod outer segments (ROS) and treated with ACC. Lysosomal volume and accumulation of autofluorescent material was measured using [14C] methylamine accumulation and FACS analysis. The regulation pattern of lysosomal proteins were investigated by proteome analysis. RESULTS: ACC reduced total lysosomal volume in control, ROS and oxidized ROS fed RPE cells. After ROS incubation increased accumulation of autofluorescent material was measured. ACC treatment decreased intracellular accumulation. Furthermore, incubation with ACC leads to a general down regulation of lysosomal proteins. CONCLUSION: In our cell culture model of ROS fed RPE cells simulating aged RPE ACC improves lysosomal volume and metabolism. Therefore ACC may represent a new prophylactic and causal treatment option for AMD.

[Subcutaneous leiomyosarcoma metastatic to the eyelid]. / Lidmetastase eines subkutanen Leiomyosarkoms.

BACKGROUND: Metastatic eyelid lesions are rare. Most metastatic lesions to the eyelid are carcinomas. Leiomyosarcomas are soft tissue sarcomas arising most commonly in the uterus and gastrointestinal tract, whereas dermal leiomyosarcomas are less frequent. Dermal leiomyosarcomas metastatic to the eyelid have not been reported so far. CASE REPORT: A 28-year-old female patient presented with a rapidly growing tumor of her right lower eyelid. A subcutaneous leiomyosarcoma of the neck had been excised 21 months before with subsequent radiotherapy. Seven months later metastases to the lung, liver, and left upper arm were detected. The patient received chemotherapy. The eyelid tumor was completely excised. Histologically the lesion consisted of spindle cells arranged in fascicles with perinuclear vacuoles and myofilaments. There was a strong immunoreactivity for smooth muscle actin, and negative staining for cytokeratin and S100. CONCLUSION: Cutaneous and subcutaneous leiomyosarcomas occur at almost any age, but are most common between the 5th and 7th decades. They are more common in men and usually occur at the extremities. The prognosis of cutaneous/subcutaneous leiomyosarcoma correlates with the depth of the tumor. To our knowledge this is the first presentation of a subcutaneous leiomyosarcoma metastatic to the eyelid. Presumably, parenchymatous metastases of this tumor occur before dermal metastases arise.

[Molecular genetic and histopathological examinations for genotype-phenotype analysis in patients with TGFBI-linked corneal dystrophy]. / Molekulargenetische und histopathologische Untersuchungen zur Genotyp-Phänotyp-Analyse bei Patienten mit TGFBI-gekoppelten Hornhautdystrophien.

PURPOSE: Different missense mutations in the TGFBI gene cause granular (Groenouw CDGG1, Avellino CDA, Reis-Bücklers CDB1) and lattice (Type I; Biber-Haab-Dimmer; CDL1) corneal dystrophies and, in some reports, corneal dystrophy Thiel-Behnke (CDB2). We report on the mutation spectrum and the genotype-phenotype correlations on the basis of clinical and histopathological examinations of 13 German families with TGFBI-linked corneal dystrophies. METHODS: In 31 patients with different corneal dystrophies, DNA was extracted from leukocytes of the peripheral blood and mutation analysis was performed by direct sequencing of the TGFBI gene. Clinical and histopathological findings were compared with the molecular genetic findings for genotype-phenotype correlations. RESULTS: In 6 patients (2 families/one single person) with clinical and histopathological CDL1 we found a Missense mutation Arg124Cys and in 7 patients (3 families/one single person) with clinical and histopathological CDA we found a Missense mutation Arg124His in the exon 4 of the TGFBI gene. In 12 patients (4 families/2 single persons) with clinical and histopathological CDGG1 we found a Missense mutation Arg555Trypt in the codon 12 of the TGFBI gene. In all five patients (1 family/4 single persons) with clinical and histopathological CDB2 we could not find any mutation in the TGFBI gene. In one patient with exceptional clinical and histopathological findings we found a Missense mutation Ala546Asp, which was reported before only twice in connection with polymorphous corneal amyloidosis. CONCLUSIONS: In comparison of our clinical and histopathological findings and the molecular genetic results we found a strong genotype-phenotype correlation in patients with TGFBI-linked corneal dystrophies. Rare mutations can lead to exceptional clinical and histopathological findings which cannot be classified into the different groups of corneal dystrophies. In our patients with CDB2 we could not find any molecular genetic correlation to the TGFBI gene.

[Central serous chorioretinopathy--retinal function and morphology: microperimetry and optical coherence tomography]. / Chorioretinopathia centralis serosa--Netzhautfunktion und -morphologie: Mikroperimetrie und optische Kohärenztomografie im Vergleich.

BACKGROUND: The purpose of this study was to evaluate and compare retinal function and morphology in patients with central serous chorioretinopathy (CSC) using fundus perimetry and optical coherence tomography (OCT). PATIENTS AND METHODS: In 14 eyes of 14 patients with unilateral and first manifestation of CSC, fundus perimetry with the Microperimeter 1 (MP1) as well as OCT were carried out. The average retinal thickness and the average differential light threshold of the corresponding visual field were analyzed. RESULTS: All patients presented a serous detachment of the central neurosensory retina with a maximal retinal thickness of 381+/-82 microm. The microperimetric examination revealed on average a mean defect of 8.3+/-3.8 dB, which showed a good correlation to retinal thickness (r=0.73). Likewise, maximal retinal thickness and mean threshold values in the corresponding visual field displayed a good correlation (r=-0.58). CONCLUSION: The MP1 enables quantification of functional defects in patients with CSC. Although visual acuity was only slightly reduced, all patients showed extensive scotomata in fundus perimetry, which correlated well with retinal thickness.

[Static fundus perimetry in normals. Microperimeter 1 versus SLO]. / Statische Fundusperimetrie bei Probanden. Microperimeter 1 versus SLO.

BACKGROUND: The Microperimeter 1 (MP-1) allows for fundus-controlled static perimetry of the central visual field. The purpose of this study was to compare MP-1 fundus perimetry with the already established scanning laser ophthalmoscope (SLO) fundus perimetry concerning detected threshold values of light increment sensitivity in normals. METHOD: In 31 eyes of 31 healthy volunteers a fundus controlled static threshold perimetry was carried out each with the MP-1 (Nidek Technologies) and the SLO (Rodenstock). In the central 21 degrees x 12 degrees visual field light increment sensitivity threshold values for 40 corresponding stimulus locations were compared in a rectangular 3 degree-grid. RESULTS: The average light increment sensitivity was 19.1+/-0.5 dB with the MP-1 and 17.2+/-0.9 dB with the SLO. On average the threshold values of the 40 corresponding test locations were 1.9+/-1.3 dB higher with the MP-1 than with the SLO. CONCLUSION: Both the MP-1 and SLO offer the possibility of a reproducible functional analysis of the central retina under simultaneous fundus control. For comparison of results of the MP-1 and SLO fundus perimetry, a correction factor of approximately 2 dB should be used.

[Radial optic neurotomy for central retinal vein occlusion -- how deep should it be?]. / Wie tief muss die radiäre Optikusneurotomie zur Therapie des retinalen Zentralvenenverschlusses sein?

PURPOSE: Most of the studies on radial optic neurotomy (RON) have not defined the depth of the incision. Complications following a deeper incision have been described. This histological study was performed to evaluate the required depth for RON. METHODS: Serial sections of the area of the optic nerve head were performed in 19 eye bank eyes. The distance between the inner surface of the optic disc and the outer limit of the cribriform plate was measured. Ten additional eye bank eyes underwent 2 mm deep experimental RON using the Spaide CRVO Knife (DORC, Netherlands). The cutting depth was assessed histologically by serial cuts. RESULTS: The distance between the inner surface of the disc and the outer limit of the cribriform plate measured 1.35+/-0.3 mm (shrinkage-revised value: 1.45 mm). The experimental RON showed cutting depths of 1.53+/-0.3 mm (shrinkage-revised value: 1.65 mm). CONCLUSION: Based on normal eyes, a cutting depth of 1.45 mm is sufficient to cut through the cribriform plate. This might change during central retinal vein occlusion because possible papillary edema due to central retinal vein occlusion has to be considered. Even under controlled experimental conditions RON leads to great variation in incision depths. The development of a knife with a fixed penetration depth would be helpful.

[Neurodermatitis. A risk factor for the development of squamous cell carcinoma]. / Neurodermitis. Ein Risikofaktor für die Entstehung konjunktivaler Plattenepithelkarzinome.

Squamous cell conjunctival carcinomas (SCCC) are rare. We report on a 34-year-old patient with neurodermatitis and chronic conjunctivitis who presented with a therapy-resistant corneal ulcer induced by mechanical irritation diagnosed as SCCC. Chronic blepharoconjunctivitis seems to sustain the development of SCCC in patients with neurodermatitis because of their insufficient immune response.

[Measurement method for the determination of rotation and decentration of intraocular lenses]. / Messmethode zur Bestimmung der Rotation und der Dezentrierung von Intraokularlinsen.

PURPOSE: In the past 50 years the IOL has been improved. Nowadays it is possible to exactly calculate the necessary IOL power and correct toric refractive errors. In this study we developed methods for measuring rotation and decentration using the example of a hydrophilic acrylic IOL. METHODS: Following cataract surgery, the first retroilluminated photograph was taken. The position of the IOL was determined with the image analysis program Adobe Photoshop. RESULTS: Measurement of a rotational movement or of a decentration of an IOL can be done accurately and rapidly. Evaluation of the stability of rotation of the hydrophilic acrylic IOL measured here showed an average rotation of the IOL of 5.3+/-1.4 degrees after 6 months compared to the position directly after implantation. CONCLUSION: The measurement methods presented here are easy to use and provide reliable results. Examiners must have basic knowledge of the computer programs used. Also, these methods depend on good quality of the retroilluminated photographs.

[Immunohistochemical detection of enhanced deposition of isoprostane 8-epi-PGF2alpha in vascular lesions of temporal arteritis]. / Immunhistochemischer Nachweis einer verstärkten Anreicherung von Isoprostan 8-epi-PGF2alpha in den Gefässläsionen bei Arteriitis temporalis.

BACKGROUND AND PURPOSE: Oxidative injury caused by lipid oxidation is considered a major factor in the development of several ocular disorders including temporal arteritis. This study investigates the role of 8-epi-PGF2alpha as a marker of oxidative stress in vivo. PATIENTS AND METHODS: Sections from isolated human temporal arteries, obtained from patients suspected of having giant cell arteritis ( n=22), were analyzed by semiquantitative immunohistochemistry and planimetry. RESULTS: Immunoreactivity for 8-epi-PGF2alpha was significantly higher in patients with temporal arteritis (AT) compared to healthy temporal arteries (Co). The percentage of the areas stained positive in immunohistochemistry was higher in the AT group compared to the control group (Co). The enrichment values in the intimal layer containing the endothelium of the same temporal arteries were also significantly higher ( p<0.01) in temporal arteries of the AT group. CONCLUSIONS: Our findings of an enhanced accumulation of 8-epi-PGF2alpha in areas of the arterial wall subjected to extensive vascular tissue destruction suggest that lipid peroxidation products may also play a role in the pathogenesis of this disease.

[Classification of ocular surface disease. Part 1]. / Klassifikation der Erkrankungen der Augenoberfläche. Teil I.

The ocular surface consists of the lid margin, conjunctiva and cornea which together with the tear system represent a functional entity. The diagnosis of ocular surface disease can be very difficult due to the similarity of various disease entities. The classification should be made on the pathological and pathophysiological characteristics of ocular surface disease. The first part of the classification comprises diseases of the lid margin, the tear system as well as diseases of the conjunctiva. Both the clinical presentation as well as the underlying pathophysiological and pathological characteristics of the most important ocular surface diseases are reviewed.

[Immunohistochemical detection of altered low density lipoprotein (ox-LDL) in the vessel walls of patients with giant cell arteritis]. / Immunhistochemischer Nachweis veränderter Low-density-Lipoproteine (ox-LDL) in der Gefässwand bei Patienten mit Arteriitis temporalis.

BACKGROUND AND PURPOSE: Recent data indicate that lipid peroxidation is implicated in the pathogenesis of giant cell arteritis with a close anatomic relationship between reactive oxygen species and oxidatively injured vascular tissue. PATIENTS AND METHODS: Immunohistochemistry utilizing anti-ox-LDL was performed on paraffin sections of isolated temporal arteries obtained from patients (n=23) suspected of having temporal arteritis. Enrichment as well as staining intensity of ox-LDL in vascular tissue was analysed by digital image planimetry. RESULTS: Temporal arteries with biopsy proven temporal arteritis (n=11) presented with significantly higher enrichment of ox-LDL in the intima (16.9+/-4.2% vs. 11.25+/-2.3%; p<0.01) and mean (9.6+/-2.4% vs. 6.75+/-1.8%; p<0.01) as compared to healthy controls. Comparable results for the staining intensity were found in the intimal (2.8+/-0.5 eU vs. 1.7+/-0.4 eU; p<0.01) and medial layer (1.55+/-0.5 eU vs. 1.04+/-0.6 eU; p<0.01) of diseased patients compared to controls. CONCLUSIONS: Accumulation of ox-LDL in the intimal layer, especially at the intima-media-border, was closely related to disruption of the elastica interna and adjacent vascular tissue, presumably contributing to the underlying process of intimal hyperplasia through unimpeded migration of smooth muscle and accumulation inflammatory cells.

[Progressive peripunctal nevus in an adult]. / Progredienter Nävuszellnävus des Punctum lacrimale im Erwachsenenalter.

Nevi arise from migration of melanocytes into the epithelium. Over the years they experience a typical maturation, with the possibility of an increased thickness due to accompanying inflammation or fibrosis but actual growth of nevi is rare in adults. A 70-year-old patient presented with a growing tumour around the punctum lacrimale. The histological examination revealed a conjunctival nevus without any transformation. Peripunctal nevi are rare. The localisation of a nevus in the area of the punctum lacrimale was first published in 1931 and only 10 other patients with such a nevus have been reported. If at all, an enlargement of a peripunctal nevus has been described in younger patients. The patient presented here showed significant growth of the nevus at an atypically high age without any histological signs of malignancy or proliferation. The reason for this uncommon nevus enlargement remains unclear.

Intraocular pressure more reduced during anesthesia with propofol than with sevoflurane: both combined with remifentanil.

BACKGROUND: Short-acting anesthetic agents are suitable and commonly used in ocular surgery. Propofol and remifentanil are known to reduce intraocular pressure (IOP), but no information is available regarding the effects of sevoflurane combined with remifentanil on IOP. METHODS: Therefore, a prospective, randomized study was conducted to compare the effects on IOP of two different anesthetic techniques: one based on a total intravenous anesthesia with propofol (Group P, bolus 1.5-2.0 mg/kg, maintenance 3.0-7.0 mg/kg/h); and the other based on sevoflurane (Group S, inhalational induction, end-tidal concentration 0.7-1.2 vol.%). An infusion of remifentanil (10 microg/kg/h) was used with both techniques. In ASA I-III patients with normal IOP undergoing elective cataract surgery, using an applanation tonometer, IOP was measured contralateral to the operated eye at nine predefined time points before, during and after anesthesia. RESULTS: The two groups (n=20 each) were comparable with regard to demographic data and hemodynamic variables. Baseline IOP was 14.2+/-2.8 mmHg (Group P) and 14.1+/-2.4 mmHg (Group S; NS). During and following the induction of anesthesia, IOP was reduced in both groups. Intraocular pressure was significantly lower in Group P (6.0+/-3.2 mmHg) than in Group S (8.9+/-3.4 mmHg) during the induction of anesthesia. CONCLUSION: In patients undergoing cataract surgery under general anesthesia with tracheal intubation, anesthetic regimens with propofol as well as with sevoflurane, both combined with remifentanil, decrease IOP significantly. The decrease in IOP was significantly more pronounced in the propofol group than in the sevoflurane group.

Fundus autofluorescence and development of geographic atrophy in age-related macular degeneration.

PURPOSE: To describe the development of new and enlargement of preexisting atrophy confined to areas with abnormally high levels of in vivo autofluorescence in eyes with geographic atrophy (GA) associated with age-related macular degeneration (ARMD). METHODS: The spatial distribution and intensity of fundus autofluorescence as well as the spread of GA and occurrence of new GA was recorded over a period of 3 years in three patients with ARMD using a confocal scanning laser ophthalmoscope. RESULTS: A diffuse irregular increased autofluorescence at the posterior pole was recorded at baseline in the presence of unifocal or multifocal patches of geographic atrophy. Within these areas of elevated autofluorescence, new atrophic areas developed, and existing patches of atrophy enlarged during the review period, whereas this was not observed in areas with normal background autofluorescence. The total area of abnormal autofluorescence also showed enlargement over time. CONCLUSIONS: These preliminary findings suggest that areas of increased autofluorescence precede the development and enlargement of outer retinal atrophy in eyes with ARMD. Because the dominant fluorophores of fundus autofluorescence are part of lipofuscin granules of RPE cells, the observations indicate that excessive RPE lipofuscin accumulation may be of significance in the pathogenesis of GA associated with ARMD. With GA being a major cause for severe visual loss in ARMD, in vivo fundus autofluorescence recording over time may allow identification of prognostic determinants and may give important clues to the understanding of mechanisms of disease.