Comparability of input parameters in the German Retina.net ROP registry and the EU-ROP registry - An exemplary comparison between 2011 and 2021.

PURPOSE: The German Retina.net ROP registry and its Europe-wide successor, the EU-ROP registry, collect data from patients treated for ROP. This analysis compares input parameters of these two registries to establish a procedure for joint analyses of different registry data using exemplary datasets from the two registries. METHODS: Exemplary datasets from the two databases over a 1-year period each (German Retina.net ROP Registry, 2011, 22 infants; EU-ROP Registry, 2021, 44 infants) were compared. The parameters documented in the two databases were aligned and analysed regarding demographic parameters, treatment modalities, complications within first 24 h and retreatments. RESULTS: The current analysis showed that data can be aligned for joint analyses with some adjustments within the data structure. The registry with more detailed data collection (EU-ROP) needs to be reduced regarding granularity in order to align the different registries, as the registry with lower granularity determines the level of analyses that can be performed in a comparative approach. In the exemplary datasets, we observed that the overall most common ROP severity in both registries was zone II, 3+ (2011: 70.5%; 2021: 65%), with decreasing numbers of clock hours showing preretinal neovascularisations (2011: 10-12 clock hours in 29% of cases, 2021: 4-6 clock hours in 38%). The most prevalent treatment method was laser coagulation in 2011 (75%) and anti-VEGF therapy in 2021 (86.1%). Within the anti-VEGF group, all patients were treated with bevacizumab in 2011 and with ranibizumab in 2021. Retreatment rates were comparable in 2011 and 2021. CONCLUSION: Data from two different ROP registries can be aligned and jointly analysed. The analysis reveals a paradigm shift in treatment modalities, from predominantly laser to anti-VEGF, and within the anti-VEGF group from bevacizumab to ranibizumab in Germany. In addition, there was a trend towards earlier treatment in 2021.

[Treated cases of retinopathy of prematurity in Germany : 5-year data from the Retina.net ROP registry]. / Behandelte Frühgeborenenretinopathie in Deutschland : 5-Jahres-Daten des Retina.net ROP-Registers.

BACKGROUND: Retinopathy of prematurity (ROP) is one of the main reasons for childhood blindness. The number of infants requiring treatment, however, is low for individual centers. The Retina.net ROP registry has been founded to allow a joint analysis of treatment patterns and courses post treatment. OBJECTIVE: This paper reports treatment patterns over 5 years. MATERIAL AND METHODS: All infants born between January 2011 and December 2015 who were entered into the treatment registry by one of the 12 participating centers were analyzed. RESULTS: The data of 150 infants (292 eyes) were analyzed and ROP 3+ in zone II was the most prevalent treatment indication. Gestational age and birth weight remained stable over the years. The treatment patterns, however, changed with anti-VEGF treatment (bevacizumab or ranibizumab) accounting for only 10% of treated eyes in 2011 but for 56% and 30% in 2014 and 2015, respectively. Almost all eyes with AP-ROP or zone I disease received anti-VEGF treatment. Zone II disease was predominantly treated with laser photocoagulation. Recurrences were more common and appeared later in the anti-VEGF group compared to the laser group (23%/interval 60 days vs. 17%/interval 23 days). Perioperative complications were evenly distributed across treatment groups. CONCLUSION: The data in this analysis represent about 10-15% of treated infants in Germany. The results provide evidence for an increasing use of anti-VEGF agents for ROP. The data reflect a selection bias for anti-VEGF treatment in eyes with a more aggressive disease. This needs to be considered when interpreting data such as disease recurrence rates. The risk for late recurrences after anti-VEGF treatment is of particular clinical significance.

NF1 mutations in conjunctival melanoma.

BACKGROUND: Conjunctival melanoma is a potentially deadly eye tumour. Despite effective local therapies, tumour recurrence and metastasis remain frequent. The genetics of conjunctival melanomas remain incompletely understood. METHODS: A large cohort of 63 conjunctival melanomas was screened for gene mutations known to be important in other melanoma subtypes by targeted next-generation sequencing. Mutation status was correlated with patient prognosis. RESULTS: Frequent mutations in genes activating the MAP kinase pathway were identified. NF1 mutations were most frequent (n = 21, 33%). Recurrent activating mutations were also identified in BRAF (n = 16, 25%) and RAS genes (n = 12, 19%; 11 NRAS and 1 KRAS). CONCLUSIONS: Similar to cutaneous melanomas, conjunctival melanomas can be grouped genetically into four groups: BRAF-mutated, RAS-mutated, NF1-mutated and triple wild-type melanomas. This genetic classification may be useful for assessment of therapeutic options for patients with metastatic conjunctival melanoma.

[Malignant lymphomas of the eye]. / Maligne Lymphome des Auges.

The eye and the ocular adnexae are rare sites for malignant non-Hodgkin lymphoma (NHL). Based on their anatomical location, intraocular lymphomas must be discerned from NHL of adnexal structures including conjunctiva, lacrimal gland, and orbit. Whereas the latter group mostly consists of indolent extranodal marginal zone B­cell lymphomas of mucosa-associated lymphoid tissue (MALT) type or secondary manifestations of systemic NHL, most primary intraocular lymphomas are classified as diffuse large B­cell lymphomas (DLBCL) and are considered a variant of primary DLBCL of the central nervous system. The most common form is primary vitreoretinal lymphoma (PVRL), which presents with nonspecific symptoms and is difficult to discern from uveitis. Diagnosis of PVRL is usually made by cytological, immunocytochemical, and molecular analysis of vitreous aspirates. Degenerative changes, limited material, and the occurrence of pseudoclonality in the molecular analysis of B­cell clonality can hamper diagnostic assessment. Novel techniques such as detection of MYD88 mutations common in PVRL can increase diagnostic sensitivity. Close cooperation with clinical colleagues and rapid specimen processing are fundamental for successful diagnosis.

[Immunotherapy of uveal melanoma: vaccination against cancer. Multicenter adjuvant phase 3 vaccination study using dendritic cells laden with tumor RNA for large newly diagnosed uveal melanoma]. / Immuntherapie beim Aderhautmelanom: Vakzination gegen Krebs. Multizentrische adjuvante Phase-III-Impfstudie mit Tumor-RNA-beladenen dendritischen Zellen bei neu diagnostizierten, großen Uveamelanomen.

Uveal melanomas are the most common malignant tumors of the eye. With modern molecular biological diagnostic methods, such as chromosome 3 typing and gene expression analysis, these tumors can be categorized into highly aggressive (monosomy 3, class II) and less aggressive forms. This molecular biological stratification is primarily important for determining the risk of these tumors as no therapy is currently available that is able to prevent or delay metastases. A randomized study of patients with a poor prognosis (monosomy 3) is currently being carried out in order to determine whether a cancer vaccine prepared from autologous (patient's own) dendritic cells and uveal melanoma RNA can prevent or delay progression and further metastases of this extremely aggressive form of cancer. Inclusion in the uveal melanoma study, which hopes to provide a potential therapeutic option for patients, is only possible if patients are referred to an institution that is able to manufacture and provide this vaccination before the patient is operated on or treated with radiation. Untreated tumor material is necessary for producing the vaccine on an individualized patient basis.

[Diagnostics and treatment of choroidal lymphoma]. / Diagnostik und Therapie der choroidalen Lymphome.

Choroidal lymphoma is a rare disease and can be classified into primary and secondary choroidal lymphomas. Primary choroidal lymphoma is a low-grade extranodal marginal zone B-cell lymphoma and secondary choroidal lymphomas present ocular manifestations of disseminated systemic lymphomas. Typical clinical features of choroidal lymphoma are multifocal, yellow-whitish choroidal infiltrates. The vitreous body is usually clear and cell-free. Choroidal lymphoma has a tendency to extend through the sclera. In contrast to primary choroidal lymphoma, which is more often unilateral, does not show signs of anterior segment involvement and has a slow progression, secondary choroidal lymphoma is more often bilateral, has a rapidly progressive course with anterior segment and vitreous involvement and belongs to the high-grade lymphomas. The definitive diagnosis of choroidal lymphoma can only be confirmed by histopathological examination of biopsy tissue. The choroidal biopsy is the gold standard in the diagnostics of choroidal lymphoma. To date, no standardized treatment for choroidal lymphoma has been established. The treatment modalities include external beam radiotherapy, immunotherapy with rituximab and chemotherapy. The prognosis for survival of primary choroidal lymphoma is usually good. The prognosis of secondary choroidal lymphoma depends on the malignancy grade of systemic lymphoma.

TERT promoter mutations in ocular melanoma distinguish between conjunctival and uveal tumours.

BACKGROUND: Recently, activating mutations in the TERT promoter were identified in cutaneous melanoma. We tested a cohort of ocular melanoma samples for similar mutations. METHODS: The TERT promoter region was analysed by Sanger sequencing in 47 uveal (ciliary body or choroidal) melanomas and 38 conjunctival melanomas. RESULTS: Mutations of the TERT promoter were not identified in uveal melanomas, but were detected in 12 (32%) conjunctival melanomas. Mutations had a UV signature and were identical to those found in cutaneous melanoma. CONCLUSION: Mutations of TERT promoter with UV signatures are frequent in conjunctival melanomas and favour a pathogenetic kinship with cutaneous melanomas. Absence of these mutations in uveal melanomas emphasises their genetic distinction from cutaneous and conjunctival melanomas.

[The melanocyte and the eye: a review with special emphasis on the cornea]. / Der Melanozyt und das Auge: eine Übersicht unter besonderer Berücksichtigung der Kornea.

BACKGROUND: Various publications especially from the field of dermatology have indicated in the recent years that the melanocyte is a "multitalent" with--besides UV-protection--(neuro-)humoral and immunological functions. Moreover, the melanocyte could play a role as a scavenger of free radicals or in pressure perception, so that it could even perhaps be part of the "intraocular pressure sensor". It is generally assumed that the cornea is devoid of melanocytes under physiological conditions. However, to the best of our knowledge a systematic investigation with a larger quantity of specimens has not been performed thus far. METHODS: 103 corneal specimens (whole eyes, corneal explants with different corneal diseases, corneoscleral donor buttons) and 13 pterygia (corneal part) were studied immunohistochemically using the monoclonal antibody Melan A which is specific for melanocytes. RESULTS: In healthy cornea melanocytes are found in the limbal area. In the corneal periphery, up to 1 mm distant from the limbus, the melanocytes disappear so that the mid-peripheral and the central epithelium of the cornea are devoid of melanocytes. Under pathological conditions (dystrophies, scars, ulcers) there is only exceptionally an invasion of melanocytes into the mid-peripheral corneal epithelium. The central epithelium almost always remains free of melanocytes even in various corneal diseases. In more than 50% of the pterygia melanocytes can be found in the epithelium. CONCLUSIONS: Under certain, pathological conditions melanocytes can settle in more central regions of the corneal epithelium. Thus, the very few "corneal melanomas" described in the literature could have theoretically developed within the cornea itself (and not within the limbus). Obviously, the cornea possesses mechanisms to inhibit centripetal migration of melanocytes perhaps via a (still hypothetic) "corneal melanocyte suppression factor" ("CoMeSuF"). To identify this factor will be the task for the coming years. If this factor is really existent it could possibly serve as a therapy for melanocytic proliferations (melanomas).

[Ocular manifestations in xeroderma pigmentosum]. / Augenmanifestationen bei Xeroderma pigmentosum.

BACKGROUND: The aim of this study was to evaluate ocular changes in patients with xeroderma pigmentosum (XP) and Cockayne syndrome (CS). Both diseases belong to the progeroid syndromes caused by single gene mutations with premature aging. Both syndromes are very rare autosomal recessive diseases caused by a gene defect leading to deficient DNA repair. PATIENTS: 12 patients (4 female, 8 male) with XP between 3 and 67 years old and a 39-year-old female patient with CS were examined. The examination included visual acuity testing, slit lamp biomicroscopy, funduscopy and performance of a Schirmer test. RESULTS: Changes of the lids in the XP group included blepharitis in 7 patients, distichiasis in 2, and madarosis in 3 patients. 8 patients had multiple lentigines solares of the lids. One patient showed scars of the lower lids after excision of a squamous cell carcinoma and a basal cell carcinoma. Conjunctival lesions comprised a tumour of unknown origin of the conjunctiva in 1 patient, teleangiectasia of the conjunctiva in 5 patients, pterygia in 4, and pinguecula in 1 patient. Two patients had an intraepithelial melanosis of the conjunctiva, and one showed conjunctival nevi. Two patients had corneal scars and corneal vascularisation, another a significant conjunctivalisation of the cornea. A Schirmer test was feasible only in 3 patients. Tear production was markedly reduced in all these patients. Break-up time was shortened significantly in 6 patients examined. The patient with the CS showed atrophy of the pupillary rim and a subcapsular cataract. Funduscopically there were pigment epithelial changes. CONCLUSIONS: Patients with XP often exhibit ocular changes. Beside the light-dependent degenerative and inflammatory manifestations at the lids, the conjunctiva and the cornea patients with XP also develop malignancies early in life. The majority of patients suffer from dry eye symptoms.

[Bilateral tumors of the eyebrows]. / Bilaterale Augenbrauentumoren.

We report about a 5-year-old boy who presented in our clinic with bilateral, slowly progressive solid tumors of the eyebrows. Histological examination of the excised tumors revealed the typical diversified picture of pilomatrixoma with basophilic and shadow cells. The bilateral or multiple manifestation of pilomatrixoma is uncommon and can be associated with myotonic dystrophy, sarcoidosis or Gardner's syndrome.

[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.

["Loose eye"]. / "Loses Auge". Diagnose: Akzidentelle Selbstenukleation (Avulsio bulbi) mit typischen Dissektionsebenen.

An extremely rare type of injury is presented: unintentional traumatic self-enucleation.

[Asteroid hyalosis within an epiretinal membrane]. / Asteroide Hyalose in einer epiretinalen Membran.

CASE REPORT: In May 2007 an 80-year-old man with a known proliferative diabetic retinopathy presented in our outpatient department with a decrease in visual acuity of his right eye. There was a thick asteroid hyalosis preventing fundus examination. Sonographically, there were vitreoretinal tractions requiring a vitrectomy. During surgery an epipapillary membrane was removed. RESULTS: Microscopically round amorphous bodies were conspicuous which were slightly basophilic in the H&E stain. The amorphous bodies were strongly positive in the periodic acid-Schiff staining. They were embedded in a fibrovascular stroma and partly surrounded by inflammatory cells with numerous giant cells of foreign body reaction. CONCLUSION: Asteroid hyalosis is a common degenerative disorder in the vitreous body. The aetiology and the pathogenesis of the asteroid bodies are not yet fully understood. An association of asteroid hyalosis with systemic diseases like diabetes mellitus, arterial hypertension, hyperlidpidaemia and atherosclerotic vasculopathy is postulated. Normally, therapy for an asymptomatic asteroid hyalosis is not necessary. The tractive proliferative diabetic retinopathy in our patient did require surgery. The incorporation of hyaloid bodies into an epiretinal membrane with the induction of a foreign body reaction is unusual.

[Tuberous sclerosis: an interdisciplinary diagnosis]. / Tuberöse Sklerose: eine interdisziplinäre Diagnose.

BACKGROUND: Tuberous sclerosis is a relatively rare disease, but it often takes a progressive and severe course. We wish to demonstrate the typical changes in a patient with tuberous sclerosis and their relevance for the ophthalmologist. FINDINGS: Ophthalmologic evaluation including funduscopy, 30 degree perimetry and fundus photography and clinical course of a 40-year-old man are described. We observed an elevated, multinodular, opaque hamartoma resembling mulberries, approximately (1/3)-(1/2) PD large, at the temporal superior arc with corresponding visual field defects. CONCLUSIONS: An ophthalmologist should always think of a tuberous sclerosis as a differential diagnosis when confronted with a retinal hamartoma. Other characteristic ophthalmological findings include facial and eyelid angiofibromas, coloboma of the iris, lens and choroid, strabismus, poliosis of the eyelashes, papilloedema and sector iris depigmentation. Clinical diagnosis of tuberous sclerosis is in most cases relatively easy; however, an interdisciplinary cooperation is needed.