[Morphologic Corneal Changes after Crosslinking for Keratoconus]. / Morphologische Hornhautveränderungen nach Crosslinking bei Keratokonus.

Keratoconus is a relatively common (1 : 2000) bilateral disease leading to a change in biochemical and biomechanical corneal structure as well as thinning and ectasia. For more than 10 years, crosslinking has been a therapeutic option in cases of progression. Using riboflavin and UVA-radiation, the anterior corneal stroma (300 µm) gets stiffened by crosslinking of collagen fibers. When protocols and limitations are adhered, the procedure is described to be effective and of low-risk. This review gives an overview about physiologic and pathologic changes in keratoconic corneas before and after crosslinking. Based on histopathologic examination, the current knowledge in published literature is reviewed and is complemented by our own investigations.

[Blepharitis - When to Perform Surgery?]. / Blepharitis - wann greifen wir zum Skalpell?

AIM: Meibomian gland dysfunction/blepharitis is usually a harmless inflammatory process of the lid margin. However, it can be the first sign of a malignant lesion. Patients/Results: Clinical and histological findings are illustrated for 8 patients with changes in the lid margin and with the differential diagnosis of blepharitis. CONCLUSION: Tumours of the lid margin can mimic blepharitis or induce meibomian gland dysfunction. Conversely, blepharitis can present in a nodular form, which is highly indicative of a neoplasm. In these cases, surgical excision with ophthalmopathological evaluation of the tissue is mandatory, in order to reach the correct diagnosis and to treat the patient appropriately.

[Routine investigation of foetal eyes--in what way and what for?]. / Routineuntersuchung fetaler Augen--wie und warum?

The investigation of foetal eyes not only allows for the observation of ocular development. It is supportive and sometimes even mandatory for the diagnosis of systemic and ocular syndromes. This review gives an overview about the investigation of foetal eyes, their assignment to developmental stages, challenges related to the investigation of foetal eyes, clinically relevant syndromes, and academic questions. The morphological development of the eye has been investigated since the 19th century and will not be covered in this article. The investigation of foetal eyes that have been collected during the routine paediatric autopsy, is complicated by artifacts. Artifacts are the result of autolysis, fixation, and mechanical manipulation. They have to be distinguished from genuine findings. Besides the search for findings such as coloboma or cataract, the morphological classification of the foetal eye is of importance. The anterior-posterior diameter allows for the diagnosis of microphthalmia. The case reports comprise Goldenhar's syndrome, MIDAS syndrome and others. In conclusion, the investigation of foetal eyes is often helpful and critical for paediatric diagnostics and should be performed with great care.

[Clinico-pathological correlations: posterior compartment of the eye and orbit]. / Klinisch-pathologische Korrelationen: Befunde des hinteren Augenabschnitts und der Orbita.

Diseases of the posterior compartment and the orbit are characterised by histological findings, most of which can be reproduced clinically. Examples are the examination of calcifications in retinoblastoma by ultrasonography. In the present review, histological findings of tumour and other diseases of the posterior ocular compartment and the orbit are presented and correlated with the clinical pictures and imaging techniques: uveal melanoma, choroidal nevus, choroidal metastases, choroidal hemangioma, retinoblastoma, Coat's disease, sympathetic ophthalmia, pleomorphic adenoma (benign mixed tumour) of the lacrimal gland, dacryoadenitis, lymphoma, rhabdomyosarcoma, Langerhans cell histiocytosis, orbital metastases, and phthisical eyes. Histopathology is usually the gold standard for a definitive diagnosis. It is very important for residents and those in training to become familiar with clinico-pathological correlations as these provide insight in pathophysiological processes. Regarding ophthalmic surgery, ophthalmic pathology offers the possibility to study wound healing and complications. A close collaboration between clinicians and ocular pathologists allows for an optimised processing of the submitted tissue and diagnosis. Thus, pre- and postoperative care can also be improved. This outstanding knowledge that ophthalmologists have gained over the last decades and beyond, should be preserved and passed on to the next generations in order to maintain a high standard in ophthalmological care.

[The situation of ophthalmic pathology in Germany: the current status]. / Zur Situation der Ophthalmopathologie in Deutschland: eine aktuelle Bestandsaufnahme.

BACKGROUND: Ophthalmic pathology with its 150 year-old tradition is a subspecialty which since its beginning has contributed substantially to progress in ophthalmology. Nevertheless, deactivation or even termination of ophthalmopathological laboratories has occurred in the past years mainly due to economic pressure. In order to evaluate the situation and future perspectives of the existing, active laboratories in Germany and to ask for the kind of support desired from the Section for Ophthalmic Pathology of the German Ophthalmological Society (DOG) a survey was carried out using a questionnaire. RESULTS: The main results were as follows. 1. Specialised ophthalmic pathology is performed in Germany almost exclusively in laboratories integrated in university eye clinics. 2. There is close cooperation with institutes for pathology and dermatopathology. 3. The main focus is placed on the cornea, tumours of the eye and its adnexae, and the conjunctiva. 4. The number of ophthalmopathological specimens investigated per year is generally below 1000 and often below 500. 5. The diagnostic spectrum and equipment of the laboratories is generally good. 6. There are some deficits concerning ophthalmopathological education and the status of ophthalmic pathology within the clinics. 7. A considerable number of scientific publications is generated by the members of the laboratories. 8. At present there is only minimal fear that the own laboratory will be eliminated in the near future. 9. Ophthalmic pathology is established as an integral component of ophthalmology in patient care and, even more, in ophthalmic research. 10. The DOG-Section "Ophthalmic pathology" is requested to initiate stays in foreign laboratories, to initiate scientific multicentre studies, and to support activities dedicated to preserve the ophthalmopathological laboratories. DISCUSSION: For the first time valid data concerning the situation of ophthalmopathological laboratories in Germany have been collected. The information gathered can and should be used as an argument for the preservation and, if possible, even expansion of the occupation with normal and pathologic eye morphology at eye hospitals in and beyond Germany.

[Pilomatrixoma of the ocular adnexae: clinical and histologic analysis (13 cases)]. / Pilomatrixom der okulären Adnexe: Klinische und histologische Aufarbeitung von 13 Fällen.

BACKGROUND: Pilomatrixoma (calcifying epithelioma of Malherbe) is a rare benign tumour originating from the matrix of the hair root. In this study, we evaluated the clinical and histopathological characteristics of all the respective tumour specimens submitted to our laboratory since 1997. PATIENTS/MATERIALS AND METHODS: We reviewed the clinical and histologic findings of 13 pilomatrixomas localised to the ocular adnexae. Paraffin sections were stained with H&E and PAS and, in addition, immunohistochemistry was performed using markers for macrophages (CD68), for proliferative activity (Ki67), and for proliferation/apoptosis (CAS/CSE1L). RESULTS: All 13 pilomatrixomas were of reddish-livid colour and localised on the upper eyelid and/or near the eyebrow. The patients ages ranged from 4 to 84 years without preference for either gender. In 3 cases the correct diagnosis was made intraoperatively, while no pilomatrixoma was diagnosed prior to surgery. The most frequent false diagnoses were retention cyst (n = 3), atheroma (n = 2), and abscess (n = 2). There was no tumour recurrence in any of the cases within the time period presented. All 13 pilomatrixomas demonstrated the characteristic histology with areas of basophilic islands, shadow cells, calcification and a chronic granulomatous inflammation with foreign body giant cells in varying amounts. Immunhistochemical staining with anti-Ki67 and anti-CAS/CSE1L indicated a regular cellular maturation of the basophilic cells. No correlation was found between any of the histological or immunohistochemical markers and clinical parameters such as size, age and gender of the patient and duration of tumour presence prior to surgery. CONCLUSIONS: This case series represents one of the largest published so far, and underscores that pilomatrixoma can appear at any age. While it is usually not recognised clinically, it should be considered in the differential diagnosis especially for tumours of the upper eyelid. Our immunohistochemical findings support the basically benign nature of a pilomatrixoma but also point to the chronic inflammatory stimulus that can lead to complications after incomplete removal.

[Collision tumor]. / Kollisionstumor.

A 65-year-old woman presented with a painless, partially pigmented and partially hyperkeratotic tumorous lesion on the lower eye lid. Histopathologic findings of the wedge resection showed a collision tumor of a highly differentiated squamous cell carcinoma and a fibrosing basal cell carcinoma. Collision tumors involving these two components are rare, particularly in the periocular region.

[Rare presentation of a scleral nevus with progression in size]. / Seltene Präsentation eines skleralen Nävus mit Größenprogredienz.

A 52-year-old male caucasian patient presented with a limbal subconjunctival pigmentation of unknown origin with progressive enlargement over the past years. Differential diagnoses included a malignant melanocytic lesion; therefore, an excisional biopsy was performed. Prior investigations showed no ciliary body or anterior chamber angle involvement. Histological and immunohistochemical analysis revealed the rare diagnosis of a scleral nevus. The clinical, histological and immunohistochemical findings as well as the relevant differential diagnoses are discussed.

[Neovascular glaucoma: aetiology, pathogenesis and treatment]. / Neovaskularisationsglaukom: Atiologie, Pathogenese und Therapie.

Neovascular glaucoma, as a typical secondary glaucoma, is due to ocular or (earlier) systemic diseases. The formation of a fibrovascular membrane on the anterior surface of the iris (rubeosis iridis) and extending into the chamber angle leads to irreversible obliteration of the outflow system, with a corresponding rise in intraocular pressure. The most frequent cause is retinal ischaemia resulting either from vascular occlusion or from diabetic alterations. The differential diagnosis must include acute angle-closure glaucoma and uncontrolled open-angle glaucoma. Treatment is aimed at eliminating the actual cause or at least reducing the risk factors (e.g. by retinal laser coagulation), or consists in cyclodestructive procedures. Medicamentous therapy comprises anti-inflammatory agents (steroids, cycloplegic agents) and substances that reduce the production of aqueous humour (carbonic anhydrase antagonists, beta blockers). In the near future, antiangiogenic medication might be another effective option. For end-stage neovascular glaucoma, the implantation of drainage devices is also discussed.

[Recurrent keratoconjunctivitis]. / Rezidivierende Keratokonjunktivitis.

BACKGROUND: Molluscum contagiosum is a highly infectious viral disease of the skin and mucous membranes. These lesions are found particularly often in children and young adults and are generally self-limiting. Nevertheless, molluscum contagiosum lesions in close vicinity to the eyes should be actively removed if they cause conjunctival or corneal irritation. CASE REPORT: We report the case of a 14-year-old boy who was treated for approximately 9 months for recurrent chronic keratoconjunctivitis with corneal neovascularization. Careful inspection of the eyelids revealed molluscum contagiosum. After removal of the lesions on both sides, short-term anti-inflammatory therapy and long-term surface lubrication, a gradual improvement was observed so that an almost complete visual recovery was achieved. CONCLUSION: In long-standing keratoconjunctivitis refractory to treatment, special attention should be paid to the possible presence of molluscum contagiosum, particularly in children and the lesions should be promptly removed.

[Orbital metastasis of a previously unknown lung carcinoma mimicking posterior ischemic optic neuropathy]. / Orbitale Metastase eines bis dato unbekannten Lungenkarzinoms mit klinischem Aspekt einer posterioren ischämischen Optikusneuropathie.

A 65-year-old patient presented with increasing loss of vision in the right eye. A relative afferent pupillary defect as well as visual field perimetry deficits in an otherwise unremarkable eye led to the presumed diagnosis of ischemia of the optic nerve; however, further imaging revealed an extensive necrotic bronchial carcinoma in the left upper lobe metastasizing to the orbit with compression of the optic nerve. The clinical and histological features are discussed with respect to possible primary origins of orbital metastases.

Immunoreactivity against tau, amyloid precursor protein, and beta-amyloid in the human retina.

PURPOSE: Increased immunoreactivity (IR) of beta-amyloid and the amyloid-associated proteins tau and amyloid precursor protein (APP) in the brain have been linked to the pathogenesis of neurodegenerative disorders such as Alzheimer's disease. However, the expression of these proteins has not been investigated in the normal or diseased human retina. METHODS: Using immunohistochemical techniques, we examined the distribution and age-related changes of anti-tau-1, anti-tau-2, anti-APP, and anti-beta-amyloid IR in the human retina at various ages (n = 24), in retinitis pigmentosa (RP, n = 6), and in age-related macular degeneration (ARMD, n = 10). RESULTS: Tau-1 immunoreactivity was intense in the inner retinal layers and did not change with age or in RP. Eyes with ARMD showed less intense staining but exhibited a similar distribution. Tau-2 IR was faint and did not change with age but was mildly increased in the retinal pigment epithelium (RPE) of eyes with RP and in the retina of eyes with ARMD. APP IR was most prominent in the ganglion cell and nerve fiber layer, and it appeared to increase in ganglion cells of older persons and in RPE cells of eyes with RP and ARMD. Beta-amyloid IR was only detected focally in sub-RPE deposits in eyes from older persons. CONCLUSIONS: The proteins investigated in this study are present in the human retina. The staining pattern of tau is different from the brain, but it shows no age-related changes. The increased immunoreactivity of APP in retinal ganglion cells of older eyes and in RPE cells of eyes with RP and ARMD, as well as the patchy staining of beta-amyloid within sub-RPE deposits, might indicate a relationship of these proteins to retinal aging and possibly to retinal degeneration in RP.

Primary malignant melanoma of the orbit arising in a cellular blue naevus.

Primary malignant melanoma of the orbit is a rare clinical entity. We report the clinical course and present the light and electron microscopic findings in a case arising in a cellular blue naevus. While most orbital melanomas are associated with a naevus of Ota, there was no clinically visible abnormal pigmentation in our patient. The possible origin of the tumour cell and its ultrastructural features are discussed.

Orbital squamous cell carcinoma after retinal detachment surgery.

We report on a 76-year-old patient with a squamous cell carcinoma of the left orbit. The tumour had no connection with the conjunctiva but was located at the site of an encircling band which had been inserted 13 years before. A major part of the tumour presented as a well circumscribed solid mass within the extraocular tissues next to the inferior equator, but the exenteration specimen also showed tumour extension within the adjacent choroid. Histological examination showed a well differentiated keratinising squamous cell carcinoma with numerous mitotic figures and many epithelial pearls. A thorough examination in search of a primary carcinoma of the lacrimal gland or the sinus, with invasion into the orbit, or an epithelial neoplasm elsewhere suggestive of metastatic disease into the choroid did not reveal any specific pathological findings. Thus the most probable origin of the tumour seems to be epithelium which had been misplaced during retinal detachment surgery and had subsequently undergone malignant transformation.

Iris melanocytes on the posterior corneal surface in congenital glaucoma. A clinicopathological case report.

The histological and ultrastructural pathology of two corneas that were removed from an infant with congenital glaucoma prior to keratoplasty is described. Clinically, the glaucoma was suspected to be due to an inapparent congenital viral infection, although there was no serological proof. Macroscopic and light microscopic examination of the posterior corneal surface revealed an irregular network of heavily pigmented cells that were overlying an incomplete endothelium and a grossly thickened Descemet's membrane. By scanning and transmission electron microscopy, these melanin-laden cells exhibited the features of iris stromal melanocytes. No evidence of viral infection could be found. The possible mechanisms leading to this unusual morphology are considered and will be discussed in relation to current theories on the etiology of congenital glaucoma.

[Success and complications of rTPA treatment of the anterior eye segment]. / Erfolge und Komplikationen der rTPA-Behandlung am vorderen Augenabschnitt.

Recombinant tissue plasminogen activator (rTPA) is commonly used in patients with myocardial infarction. Recently, it has also been applied intraocularly to dissolve postoperative fibrin with no serious complications being reported so far. In this study we describe our own experience with rTPA in 25 patients with persisting fibrinous membranes in the anterior segment. rTPA (Actilyse, Dr. Karl Thomae GmbH) was given in a single dose of 25 micrograms and injected into the anterior chamber via a paracentesis. We did not encounter any complications during the injection of rTPA. In 21 eyes fibrin could be reduced significantly, albeit sometimes only slowly. In 13 patients, the membrane had dissolved almost completely by the following day. In contrast, no success was observed after glaucoma surgery (2 eyes) and in chronic iritis (1 eye), or when fibrin mixed with blood was treated (1 eye). There were two (controllable) post-operative hemorrhages (rTPA after vitrectomy, and for fibrin/blood after cataract surgery). In addition, we noted 2 cases of irreversible superficial corneal clouding (rTPA after cataract surgery). We conclude that injection of rTPA can be a useful addition to steroid treatment in selective cases of persisting fibrin in the anterior segment. Long-standing membranes, however, are unlikely to be dissolved. Care should also be taken and rTPA be avoided when there is evidence of recent bleeding. Most worrying to us were the corneal complications that we cannot explain to date. With regard to the definite time correlation we feel that rTPA or one of the solution components might be the cause of this unusual feature.

[Immunoscintigraphy results in the comparison of ocular with cutaneous melanoma]. / Immunszintigraphische Ergebnisse beim okulären im Vergleich zum kutanen Melanom.

For several years, immunoscintigraphy (IS) using a 99mTc-labeled monoclonal antibody for tumor localization has been used as an additional tool in the diagnosis of malignant melanoma. The aim of our study was to verify previously published data with respect to our own patients and to correlate immunoscintigraphic results with histological findings. In particular, we wanted to compare the outcome of IS in ocular melanoma with that in cutaneous melanoma. We examined 28 patients (15 females, 13 males, average age 64 years) with clinically suspected ocular melanoma. IS was performed using the monoclonal antibody 225.28S (Tecnemab-K-1, Fa. Sorin/Solco), and images were obtained in a standard fashion (planar) as well as with the SPECT technique. In 16 patients, the tumor was examined afterwards histologically. The control group consisted of 102 patients with histologically proven metastasizing cutaneous melanoma who were investigated by IS in an identical fashion. In contrast to the literature published so far, we demonstrated a positive IS reaction in only 42% (and 56% in histologically proven cases, respectively) in our patients with ocular melanoma, while in patients with cutaneous melanoma, we found a sensitivity of more than 80%. In the 3 patients who turned out not to have ocular melanoma, we found one false-positive reaction (subretinal hemorrhage). No correlation was found between the various histological features of ocular melanoma and the immunoscintigraphic results. We conclude that IS using the antibody 25.28S is of limited value in patients with ocular melanoma and should only be recommended in selected cases.(ABSTRACT TRUNCATED AT 250 WORDS)

[Antigen pattern in choroid melanoma in correlation with immunoscintigraphy]. / Antigenmuster beim Aderhautmelanom in Korrelation zur Immunszintigraphie.

We have reported that the sensitivity of immunoscintigraphy in ocular melanoma is fairly low in comparison with (metastasizing) cutaneous melanoma. No significant correlation was found between the histological data for ocular melanoma and the immunoscintigraphic results. We therefore wanted to see whether we could demonstrate an antigen pattern that was different from that of cutaneous melanoma, which might explain our previous results. Our study comprised tumor tissue from 20 patients with ocular melanoma who had undergone previous immunoscintigraphic examination. Using immunohistochemical techniques, tumor immunoreactivity was investigated against 225.28S, the antibody used for immunoscintigraphy, on cryosections in 12 cases, and against anti-HMB-45, and anti-S-100 and anti-vimentin on paraffin sections in all 20 patients. In summary, there was marked immunohistochemical heterogeneity, and none of the antibodies examined showed a significant correlation with immunoscintigraphy. Even 225.28S that was used for the immunoscintigraphic examination did not retrospectively allow a predictable immunoscintigraphic outcome. When comparing our results with the literature on cutaneous melanoma we were also able to confirm differences in immunoreactivity with regard to the other antibodies. We conclude that the comparatively poor results in ocular immunoscintigraphy obtained with 225.28S are due to antigenic differences between ocular and cutaneous melanoma.