Ultrastructural analysis of explanted CyPass microstents and correlation with clinical findings.

PURPOSE: The purpose of this study was to obtain insight into cellular processes after CyPass microstent implantation into the supraciliary space. With this knowledge, we expected to find some reason for surgical failure. METHODS: Nine CyPass microstents of 8 patients with primary open-angle glaucoma (n = 1), pseudoexfoliation glaucoma (n = 5), uveitic glaucoma (n = 1), and posttraumatic open-angle glaucoma (n = 1) were explanted due to recurrence of IOP elevation, corneal decompensation, or persistent hypotony. The explants were processed for light and transmission electron microscopy. RESULTS: Fibrotic material, consisting of collagen fibrils, microfibrils, pseudoexfoliation fibrils produced by activated fibroblasts, was detected in the stent lumen of 4/5 pseudoexfoliation glaucoma patients and also in posttraumatic open-angle glaucoma. Fibrotic material was also present on the outer surface and within fenestrations of the majority of stents. Complete absence of fibrotic reaction was noticed in 3 of 9 microstents. CONCLUSION: Although MIGS is known to be less invasive than conventional surgery, implants placed in the suprachoroidal space may be adversely affected by a fibrotic tissue reaction resulting in implant failure. Understanding mechanisms and risk factors leading to fibrotic scarring following antiglaucomatous surgery may help to develop novel strategies that improve surgical outcome.

[The most important signs of a glaucomatous disc]. / Die wichtigsten ophthalmologischen Papillenveränderungen bei den Glaukomen.

Glaucomatous optic atrophy is the result of both primary and secondary glaucomas leading to functional defects. Loss of axons and ganglion cells leads to a specific atrophy of the optic nerve head. Increased cup size and depth with loss of neuroretinal rim tissue are accompanied by changes of the retinal vessels and juxtapapillary retinal pigment epithelium. Changes of the retinal nerve fibre layer, caused by ganglion cell loss may be earliest signs of glaucomatous atrophy. The marked variability of optic disc size and form may influence the quality of ophthalmoscopic evaluation in extreme variants. Peripapillary haemorrhages and changes of pulsation properties of the retinal venules may give prognostic information for the course of the disease. These signs may be evaluated and even semiquantitatively measured with limited technical effort. They lay the basis for the evaluation of modern imaging and measuring techniques. This article summarises criteria described by Jonas and other authors in the light of modern imaging techniques and adds the latest scientific results.

[Papilledema and echographically detectable retro-orbital dilatation of the sub-arachnoidal space with open fontanelle - six case reports]. / Stauungspapille und echografisch nachweisbare retroorbitale Erweiterung des Subarachnoidalraums bei offener Fontanelle - Sechs Kasuistiken.

This paper analyses the case reports for three children in which a papilledema occurred before the age of one year. Furthermore, an analysis is also given of three further case reports for children aged less than one year in which, in spite of open fontanelle, no papilledema was found, however, a dilatation of the sub-arachnoidal space was demonstrated echographically. Even in children less than one year of age in which an open fontanelle still exists and in whom a neuro-paediatric clarification of internal hydrocepalus is made, in spite of opththalmoscopically inconspicuous findings for the papilla an echography is indispensable for the evaluation of the sub-arachnoidal space. Here, the early recognition of a dilatation of the retro-bulbar sub-arachnoidal space can possibly prevent the occurrence of a consecutive optic atrophy. At the present time, the data available do not allow the recommendation of an upper age limit for an echographic examination.

[Clinical and sonographic examination findings in patients with carotid-cavernous sinus fistulas]. / Klinische und echographische Untersuchungsbefunde bei Patienten mit Carotis-Sinus-cavernosus-Fisteln.

BACKGROUND: Symptoms and clinical findings in patients with carotid-cavernous fistulas are specific. Nevertheless, they can be very mildly expressed. This study aims to point out the potential diagnostic value of ultrasound of the orbit. METHODS: A total of 25 patients with a reliable angiographic diagnosis of a fistula were reviewed retrospectively. We analyzed the symptoms, clinical findings and demonstrability in ultrasound of the orbit. RESULTS: The most common clinical findings were nerve palsy, dilation of episcleral vessels and exophthalmos. If an ultrasound had been part of the examination a dilation of the superior ophthalmic vein could be demonstrated in all cases. CONCLUSION: The expeditious ultrasound investigation provides valuable information for the diagnosis of red eyes which are resistant to treatment. The examiner has to consider a fistula and perform an ultrasound especially when diplopia has newly occurred. Finally, the expedient neuroimaging can be arranged.

[Long-term follow-ups of patients with glaucoma with digital planimetry]. / Digitale Planimetrie zur Langzeitverlaufskontrolle bei stabilen und progredienten Glaukomen.

BACKGROUND: The purpose of this study was to investigate whether digital planimetry is appropriate for quantification of neuroretinal rim loss in patients with glaucoma, with and without progression. PATIENTS AND METHODS: The optic discs of 44 patients, whose illness had been well documented with photographs over a period of at least eight years were divided in a progression group and an unchanged group with regard to glaucoma. After this evaluation we measured each disc by digital planimetry and correlated the results. The researcher conducting the measurements was unaware of the patients' date of examination and the diagnosis. RESULTS: While the neuroretinal rim decreased by only 0.06 A+/- 0.15 mm(2) on average in the group of patients without glaucoma, the average decrease was 0.30 A+/- 0.27 mm(2) in the group with progression. This corresponds to a yearly decrease on average of merely 0.0043 A+/- 0.011 mm(2) (0.25%/a) in the group without progression and one of 0.0228 A+/- 0.025 mm(2) (1.9%/a) in the group with progression. Mean neuroretinal rim loss was 0.25% per year in the group without progression of glaucoma, and 1.9% per year in the group with progression. This annual difference is significant. (p = 0.003). The average observation time in the morphologically better group was on average significantly shorter (12.3 years compared to 14.5 years). CONCLUSION: Digital planimetry was able to determine if a morphological progression was found in a clinical examination or if a glaucoma showed no signs of worsening. So we can use this method of digital planimetry of optic discs to examine and re-examine older and more recent photographs to always get the best results of a possible progression of glaucoma.

[Optical coherence tomography angiography: Value for glaucoma diagnostics]. / Optische Kohärenztomographie-Angiographie: Stellenwert in der Glaukomdiagnostik.

BACKGROUND: Optical coherence tomography angiography (OCTA) is a novel noninvasive method which enables a quantitative evaluation of retinal and optic nerve head (ONH) perfusion. In this article, we discuss the principles of the application of OCTA and give a summary of the knowledge gained by using this method in glaucoma patients. METHODS: This article is based on a selective literature search and the analysis of own data. RESULTS: Quantitative OCTA parameters have a good reproducibility in glaucoma patients. Glaucoma patients show a reduced flow density (FD) in the ONH and in the area of the macula compared with a healthy control group. The FD parameters show a good diagnostic discriminatory power but are not superior to the structural parameters used in routine diagnostics. The reduced FD measured using OCTA correlates with the extent of functional and structural glaucoma damage. CONCLUSION: The OCTA is noninvasive, fast and reproducible. Initial results from studies on glaucoma patients show the high diagnostic potential of this method. The OCTA could become a part of clinical glaucoma management in the future.

[Bilateral posterior persistent hyperplastic primary vitreous]. / Bilateraler posteriorer persistierender hyperplastischer primärer Glaskörper.

Bilateral persistent hyperplastic primary vitreous (PHPV) represents a rare entity of a congential malformation. This casuistic presents for the first time in the German literature the case of a 4-month-old child with bilateral posterior PHPV.

[Sympathetic ophthalmia following repeated pars plana vitrectomy : Clinical findings and spectral domain OCT follow-up]. / Sympathische Ophthalmie nach zweimaliger Pars-plana-Vitrektomie : Klinische Befunde und Spectralis-OCT-Verlauf.

Sympathetic ophthalmia is a rare form of bilateral granulomatous panuveitis, occurring after penetrating trauma. Hitherto, sympathetic ophthalmia after vitrectomy has only occasionally been described in the literature. This case report presents a female patient with sympathetic ophthalmia after repeated pars plana vitrectomy on the basis of clinical findings and follow-up with fluorescein angiography, spectral domain OCT, and histopathology.

[Cavernous sinus thrombosis as a rare cause of exophthalmos in childhood : A case report]. / Sinus-cavernosus-Thrombose als seltene Ursache eines Exophthalmus im Kindesalter : Ein Fallbericht.

Complications of acute bacterial sinusitis mostly occur in children and adolescents. In particular, intracranial spread of the infection can lead to severe even fatal courses of the disease. This article is a case report about a 13-year-old boy suffering from left-sided headache, meningismus and exophthalmos as presenting symptoms. Cranial magnetic resonance imaging (MRI) showed merely right-sided sphenoid sinusitis; however, the diffusion-weighted MRI sequence indicated a left-sided cavernous sinus thrombosis, which could be confirmed by computed tomography (CT) angiography. Cerebrospinal fluid diagnostics showed significant leukocytosis confirming secondary meningitis. Finally, exophthalmos was explained by parainfectious cavernous sinus thrombosis and periorbital edema. This case report highlights the importance of extended and specific diagnostic imaging in cases of clinically suspected complications in children and adolescents with sinusitis and the diagnostic significance of diffusion-weighted MRI.

Automated segmentation of the optic nerve head for diagnosis of glaucoma.

Glaucoma is the second most common cause of blindness worldwide. Low awareness and high costs connected to glaucoma are reasons to improve methods of screening and therapy. A well-established method for diagnosis of glaucoma is the examination of the optic nerve head using scanning-laser-tomography. This system acquires and analyzes the surface topography of the optic nerve head. The analysis that leads to a diagnosis of the disease depends on prior manual outlining of the optic nerve head by an experienced ophthalmologist. Our contribution presents a method for optic nerve head segmentation and its validation. The method is based on morphological operations, Hough transform, and an anchored active contour model. The results were validated by comparing the performance of different classifiers on data from a case-control study with contours of the optic nerve head manually outlined by an experienced ophthalmologist. We achieved the following results with respect to glaucoma diagnosis: linear discriminant analysis with 27.7% estimated error rate for automated segmentation (aut) and 26.8% estimated error rate for manual segmentation (man), classification trees with 25.2% (aut) and 22.0% (man) and bootstrap aggregation with 22.2% (aut) and 13.4% (man). It could thus be shown that our approach is suitable for automated diagnosis and screening of glaucoma.

[Principles of glaucoma diagnostics with optical coherence tomography]. / Grundlagen der optischen Kohärenztomographie-basierten Glaukomdiagnostik.

BACKGROUND: In recent years many applications of optical coherence tomography (OCT) have led to a better understanding of glaucoma morphology. The clinical routine in the treatment of glaucoma is strongly influenced by the modern diagnostic aspects. METHODS: A selective search of the literature was carried out and the important aspects are presented taking own experiences into account. The measurement principles, diagnostic ability and pitfalls of the three OCT measurement procedures are highlighted. RESULTS: Retinal nerve fiber layer, macula and ganglion cell layer thickness as well as the minimum neuroretinal rim width have facilitated in particular the objective early diagnosis and follow-up measurements. CONCLUSION: For glaucoma, OCT measurements cannot replace the medical expert diagnosis but they represent a valuable decision-making aid for diagnostics and follow-up examinations.

[Structural alterations during the course of glaucoma disease]. / Strukturelle Veränderungen im Verlauf der Glaukomerkrankung.

BACKGROUND: Structural changes in the course of glaucoma disease affect the trabecular meshwork and ciliary body in addition to the optic disc as the primary site of glaucoma damage. OBJECTIVES: Latest results from experimental studies, animal models and measurements in human eyes are presented and discussed. RESULTS: The presenting scenario is complex with age, biochemical and mechanical stress factors leading to subsequent, irreversible tissue change in the trabecular meshwork and cribriform plate of the optic nerve, resulting in neuronal tissue loss. CONCLUSION: Knowledge of these changes will be the key for future glaucoma therapies.

[Successful brachytherapy of a clinically unapparent ciliary body melanoma]. / Erfolgreiche Brachytherapie bei klinisch inapparentem Ziliarkörpermelanom.

We report on a typical case of a ciliary body melanoma in a 59-year-old female, which was only noticed due to nonspecific unilateral vision disorders and which could only be seen in maximal mydriasis via a gonioscopic three-mirror lens. We further discuss tumor monitoring via ultrasound biomicroscopy (UBM) and execution and prognosis of Ru-106 brachytherapy.

Morphometry of the human lamina cribrosa surface.

The lamina cribrosa is a sieve-like perforation in the posterior part of the sclera, that allows passage of the retinal ganglion cell axons and central retinal vessels and preserves a pressure gradient between the intraocular and extraocular space. It has been termed the primary site of glaucomatous damage to the optic nerve. Using electron microscopy, the authors morphometrically evaluated the inner surface of the lamina cribosa in 40 normal human donor eyes. There were 14 men and 21 women with a mean age of 52 +/- 22 yr (10-82 yr). Mean single pore area (0.004 +/- 0.001 mm2) and summed pore area were significantly (P less than 0.05) larger and the ratio of summed pore area to lamina area was higher in the inferior and superior regions than in the temporal and nasal regions. The ratio decreased with increasing lamina cribrosa size. Count, size, form, and density of the pores were statistically independent of age, sex, side, and lamina cribrosa form. Pore count and summed pore area (mean: 0.92 +/- 0.22 mm2) increased significantly with enlarging lamina cribrosa size. The area of the lamina cribrosa openings for passage of the central retinal vessels was independent of the lamina cribrosa size. The high ratio of summed pore area to lamina area and the large single pore area may be pathogenetically important for the increased glaucoma susceptibility in the inferior and superior disc regions. The lack of a correlation between lamina cribrosa size and the area of the lamina cribrosa openings for the retinal vessels may explain why central retinal vessel occlusions occur independently of optic disc size.

Expression of cyclooxygenase-1 and -2 in normal and glaucomatous human eyes.

PURPOSE: Primary open-angle glaucoma (POAG) is the predominant form of chronic glaucoma, but the underlying pathologic mechanisms are largely unknown. Because prostaglandins (PGs) have been introduced into POAG treatment with remarkable success, this study was undertaken to investigate whether a change in the expression of the PG-synthesizing enzymes cyclooxygenase (COX)-1 and -2 might be involved in the pathogenesis of POAG. METHODS: Expression of COX-1 and -2 was assessed by confocal laser microscopy, immunohistochemistry, Western blot analysis, and real-time RT-PCR in human eyes with different forms of glaucoma (primary open-angle, angle-closure, congenital juvenile, and steroid-induced), as well as in age-matched control eyes. Additionally, PGE2 was measured in aqueous humor by means of an enzyme-linked immunoassay as a product of COX activity. RESULTS: In normal eyes, ocular COX-1 and -2 expression were largely confined to the nonpigmented secretory epithelium of the ciliary body. By immunohistochemistry and real-time RT-PCR, COX-2 expression was completely lost in the nonpigmented secretory epithelium of the ciliary body of eyes with end-stage POAG, whereas COX-1 expression was unchanged. By immunohistochemistry, in the ciliary bodies of eyes in five patients with diagnosis of early POAG, eyes in two had complete loss of COX-2 expression and in three showed only a few remaining scattered COX-2-expressing cells. COX-2 expression in the ciliary body was also lost in patients with steroid-induced glaucoma and was reduced in patients receiving topical steroid treatment. Eyes of patients with either congenital juvenile or angle-closure glaucoma showed COX-2 expression indistinguishable from control eyes. Aqueous humor of eyes with POAG contained significantly less PGE2 than control eyes. CONCLUSIONS: Both cyclooxygenase isoforms are constitutively expressed in the normal human eye. Specific loss of COX-2 expression in the nonpigmented secretory epithelium of the ciliary body appears to be linked to the occurrence of POAG and steroid-induced glaucoma.

"Masked" pseudoexfoliation syndrome in unoperated eyes with circular posterior synechiae: clinical-electron microscopic correlation.

OBJECTIVE: To investigate the prevalence of "masked" pseudoexfoliation (PEX) syndrome in eyes with circular posterior synechiae receiving antiglaucomatous therapy with miotics. DESIGN: Cross-sectional prospective study. METHODS: Twenty-eight eyes of 27 consecutive patients with circular posterior synechiae and a history of miotic drug use without previous intraocular surgery, inflammation, or trauma, and without conventional signs of PEX material in the anterior chamber were included in the study. All eyes were investigated by slitlamp biomicroscopy and gonioscopy of the anterior chamber before extracapsular cataract surgery for the presence of typical PEX-associated iris pigment epithelial changes, such as peripupillary atrophy and trabecular meshwork melanin granule deposition. The anterior chamber depth, lens thickness, and axial lengths of the eyes were measured by A-scan immersion sonography. The excised anterior lens capsules obtained during extracapsular cataract surgery were investigated for the presence of precapsular fibrillar PEX deposits by electron microscopy. MAIN OUTCOME MEASURE: The prevalence of masked PEX syndrome in eyes with circular posterior synechiae receiving antiglaucomatous therapy with miotics. RESULTS: Transmission electron microscopy of unselected nonserial sections revealed a precapsular layer consisting of typical PEX fibers or microfibrils, which indicated early stages of PEX syndrome in 18 (64%) of 28 eyes with circular posterior synechiae. Melanin granules were frequently found adhering to the fibrillar layer. Eyes with precapsular fibrillar deposits showed significantly greater trabecular meshwork pigmentation than eyes without such deposits. Differences in age, lens thickness, axial length of the eye, anterior chamber depth, and degree of peripupillary atrophy were, however, not statistically significant between the groups with and without electron microscopic evidence of PEX deposits. CONCLUSIONS: Circular posterior synechiae were more frequently associated with manifest or early stages of PEX syndrome. However, the formation of broad posterior synechiae in miosis prevented a definite clinical diagnosis based on the classic changes of the anterior lens capsule. In eyes with spontaneous or miotic-induced circular posterior synechiae without other obvious cause, the masked variant of PEX syndrome should always be considered.

Comparison between tomographic scanning evaluation and photographic measurement of the neuroretinal rim.

PURPOSE: To compare laser tomographic scanning evaluation with photographic measurement of size and shape of the neuroretinal rim. METHODS: For 25 normal eyes and 32 glaucomatous eyes, the optic disks were examined with the Heidelberg Retina Tomograph (software version 1.11) for confocal laser tomographic scanning evaluation, and color stereoscopic optic disk photographs for planimetric measurements. Area and width of the neuroretinal rim were determined as percentages of the disk area and diameter, respectively. RESULTS: For the normal and glaucomatous eyes, the tomographic results compared with the photographic measurements disclosed significantly larger values for the relative width and relative area of the neuroretinal rim. The differences between both methods were most marked in the nasal part of the optic disk and least marked in the temporal disk region. The relative differences increased significantly (P < .05) with increasing degree of glaucomatous optic nerve damage. CONCLUSIONS: In normal and glaucomatous eyes, the Heidelberg Retina Tomograph determines the neuroretinal rim, expressed as percentage of optic disk measurements, to be significantly larger than when the rim is evaluated on optic disk photographs. Because parts of the central retinal vessel trunk are defined as neuroretinal rim in the algorithm of the Heidelberg Retina Tomograph, the differences between Heidelberg Retina Tomograph measurements and photographic determinations of the rim are largest in the nasal disk region and smallest in the temporal disk area. The neuroretinal rim shape and neuroretinal rim area differ appreciably between the two methods. These differences increase with increasing degree of glaucomatous optic nerve damage.