[Histology of the living eye : Noninvasive microscopic structure and functional analysis of the retina with adaptive optics]. / Histologie im lebenden Auge : Nichtinvasive mikroskopische Struktur- und Funktionsanalyse der Netzhaut mit adaptiven Optiken.

Equipping an ophthalmoscope with adaptive optics (AO) offers access to the living human retina with unprecedented spatial resolution. With AO, cellular structures such as the nerve fiber layer, the microvasculature of the smallest retinal capillaries, rod and cone photoreceptors and the mosaic of the retinal pigment epithelium are directly observable. A large number of studies in the normal and diseased retina have already shown that this level of detail offers new insights into disease mechanisms and progression, and promises to identify early disease markers. In conjunction with functional testing of single photoreceptors that is possible with AO microstimulation, a structure-function relationship on the cellular scale is within reach. These technological advances offer new avenues for clinical ophthalmology, interventional efforts, and basic research of the function and dysfunction of vision.

[Clinical applications of OCT angiography]. / Klinische Anwendungen der OCT-Angiographie.

BACKGROUND: Optical coherence tomography angiography (OCT-A) allows noninvasive, depth-selective visualization of retinal and choroidal vascular networks by detecting the endoluminal blood flow. This results in three-dimensional high-resolution images which are not possible by regular fluorescein angiography in this spatial resolution. Thus, OCT-A can be used to visualize the microperfusion of retinal and choroidal vessels and their alterations due to diverse pathologies and during the course of therapy. Based on several clinical case reports this article gives an overview of the wide range of applications of OCT-A. METHODS: The OCT-A images were obtained with the Spectralis OCT-2 prototype (Heidelberg Engineering, Heidelberg, Germany). This device provides an increased A scan rate of 70 kHz, which allows the generation of high-resolution OCT volume scans. RESULTS: The areas of application are manifold and include neovascular age-related macular degeneration, diabetic retinopathy, retinal vascular occlusion, inflammatory diseases and telangiectasia of various etiologies. The resulting images and their interpretation differ significantly from regular fluorescein angiography. Knowledge of these differences and of the limitations of this novel diagnostic device are of importance for its clinical application. For certain indications, OCT-A may be used as a substitute for invasive fluorescein angiography and provides more detailed information, particularly due to the absence of blockage phenomena, such as pooling or staining. CONCLUSION: The use of OCT-A allows visualization of the microperfusion of the retinal and choroidal vascular networks and their alterations due to diverse diseases in high resolution and with segmentation of different anatomical layers. The exact interpretation of the three-dimensional OCT-A images and their clinical application are currently under clinical evaluation.

[Pseudodominant inheritance of pseudoxanthoma elasticum]. / Pseudodominante Vererbung von Pseudoxanthoma elasticum.

Pseudoxanthoma elasticum (PXE) is a system disease due to mutations in the ABCC6 gene with characteristic alterations in the eyes, the skin and the cardiovascular system. Herein, we report on two families with PXE in two subsequent generations due to genetically confirmed pseudodominance. A literature review revealed that PXE due to mutations in ABCC6 follows an autosomal recessive inheritance and that disease manifestation in two subsequent generations is due to pseudodominance.

[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.

[Morphological characteristics in macular telangiectasia type 2]. / Morphologische Charakteristika bei makulären Teleangiektasien Typ 2.

Macular telangiectasia type 2 is characterized by atrophic alterations of the central retina which is accompanied by a defined vascular phenotype. The disease manifests within an oval central retinal area the size of approximately two disc diameters, with a topographic predisposition temporal to the foveal center. Funduscopy reveals reduced retinal transparency, crystalline deposits, mildly ectatic capillaries, thickened venules and retinal pigment plaques. Secondary neovascularization and macular holes may occur during the disease course. Fluorescein angiography usually shows a diffuse leakage and often ectatic capillaries. On optical coherence tomography (OCT) examination, hyporeflective cavities and focal atrophy of the photoreceptor layer represent a frequent finding. A characteristic sign is an increased (para) central signal on fundus autofluorescence imaging due to a reduced density of macular pigment.

[Functional characteristics of macular telangiectasia type 2]. / Funktionelle Charakteristika bei makulären Teleangiektasien Typ 2.

The first symptoms of macular telangiectasia type 2 usually occur between 50 and 70 years of age. Functional alterations topographically correspond to the morphological changes. Characteristic paracentral scotomata due to focal photoreceptor atrophy can be detected using microperimetry. The predominant paracentral functional loss may cause reading difficulties despite visual acuity in the range between 20/20 and 20/50. Visual acuity around 20/200 may occur once the paracentral photoreceptor atrophy extends centrally, or due to the development of a macular hole or a secondary neovascular membrane. Progression of functional loss can often only be detected by mapping scotoma size or occurrence using microperimetry, while visual acuity may remain unchanged.

[Therapeutic approaches for macular telangiectasia type 2: status quo and perspectives]. / Therapeutische Ansätze bei makulären Teleangiektasien Typ 2: Status quo und Perspektiven.

Macular telangiectasia type 2 is characterized by neurodegenerative as well as vascular and retinal alterations. Previous therapeutic approaches mainly targeted the vascular changes; however, this did not prove to be beneficial except for secondary neovascularization which may be successfully treated with intravitreal vascular endothelial growth factor inhibitors. As the natural history of the disease is primarily characterized by the neurodegenerative processes, new therapeutic strategies, such as neuroprotective agents are already being explored in clinical trials.

[Etiology and pathogenesis of age-related macular degeneration]. / Ätiologie und Pathogenese der altersabhängigen Makuladegeneration.

Age-related macular degeneration (AMD) is the most common cause of blindness in Germany. Due to the demographic development a further increase of affected patients is to be expected. Improved understanding of AMD pathogenesis resulted from the molecular biological approaches in recent years and showed an association of genetic factors with AMD. The complement factor H gene and the second high-risk locus ARMS2 in particular were found to contribute a significant risk for development of the disease. Ageing and environmental factors, such as smoking, modulate the individual genetic risk profile. A detailed understanding of the complex AMD pathogenesis is also relevant in ophthalmological practice to understand new treatment strategies. In this review we aim to give an overview of the interplay of ageing, external environmental factors and genetic risk variants leading to AMD.

Two-wavelength fundus autofluorescence and macular pigment optical density imaging in diabetic macular oedema.

PURPOSE: To evaluate the application of 488 and 514 nm fundus autofluorescence (FAF) and macular pigment optical density (MPOD) imaging in diabetic macular oedema (DMO) and to demonstrate the typical imaging features. PATIENTS AND METHODS: A hundred and twenty-five eyes of 71 consecutive patients with diabetic retinopathy who underwent examination at a specialist university clinic employing a modified Heidelberg Retina Angiograph, using two different light sources of 488 and 514 nm wavelength, were retrospectively reviewed. MPOD images were calculated using modified Heidelberg Eye Explorer software. All images were evaluated by two independent masked graders. Features from FAF and MPOD images were correlated with optical coherence tomography (OCT) imaging findings and inter-grader variability, sensitivity and specificity were calculated using OCT as reference. RESULTS: Sixty-seven eyes had DMO on OCT. The inter-grader variability was 0.84 for 488 nm FAF, 0.63 for 514 nm FAF and 0.79 for MPOD imaging. Sensitivity and specificity for detection of DMO were 80.6 and 89.7% for 488 nm FAF; 55.2 and 94.8% for 514 nm FAF; and 80.6 and 91.4% for MPOD imaging. In 488 nm FAF and MPOD imaging, DMO was better visualised in comparison with 514 nm FAF imaging, P<0.01. MPOD revealed displacement of macular pigment by intraretinal cysts. CONCLUSION: MPOD imaging, and particularly its combination with 488 nm and 514 nm FAF, provides a valuable addition to OCT in the evaluation of DMO and is clinically useful in rapid en-face assessment of the central macula.

[Gene therapy for retinal dystrophies]. / Gentherapie bei Netzhautdystrophien.

Genetic mutations are the cause of inherited retinal dystrophies. The underlying genetic basis of these diseases suggests that a gene therapy approach is logical either to replace or reduce the expression of defective genes. The first proof-of-concept clinical studies in patients with Leber's congenital amaurosis have suggested that retinal gene therapy is safe and potentially effective, at least for specific disease entities. In contrast to pharmacological treatment gene therapy has the advantage of being able to express a protein within specific cell populations and is a potentially definitive therapy. Besides replacing deficient genes in inherited diseases, additional strategies that might broaden the application of retinal gene therapy are also being developed. These include the permanent expression of neuroprotective substances or photosensitive molecules (so-called optogenetics). This overview discusses the current clinical strategies and potential problems of retinal gene therapy.

An integrated software solution for multi-modal mapping of morphological and functional ocular data.

Various morphological and functional techniques for retina examination have been established in the recent years. Although many examination results are spatially resolved and can be mapped onto data originating from other modalities, usually only data from one modality is analyzed by a clinician at a time. This is mainly because there is no software available to the public that enables the registration of structure and function in the clinical setting. Therefore we developed an integrated mapping application that allows the registration and analysis of morphological data (fundus photography, optical coherence tomography, scanning laser ophthalmoscopy images, and GDx thickness profiles) and functional data (multifocal electroretinography, multifocal pattern electroretinography, perimetry, and microperimetry). To obtain quantitative data that can be used for clinical trials and statistical analyses, extraction routines for morphological parameters - such as retinal layer thicknesses and measures of the vascular network - have been integrated. Global, regional and point-specific data from registered modalities can be extracted and exported for statistical analyses. In this article we present the implementation and examples of use of the developed software.

[Vascular lesion of the conjunctiva]. / Vaskuläre Läsion der Bindehaut.

A 44-year-old male patient first noticed a pain-free light red swelling of the right eye in 1983. Based on the results of the early indocyanine green angiography, MRI and sonography, a racemose hemangioma of the conjunctiva was diagnosed. Although a racemose hemangioma already exists at birth, it remains clinically silent for a long time and symptoms often first appear in early adulthood. In this patient external surgical excision was terminated due to substantial bleeding. A symptomatic treatment in the sense of surface care is considered to be the best option.

Characterisation of severe rod-cone dystrophy in a consanguineous family with a splice site mutation in the MERTK gene.

AIM: To characterise the ocular phenotype of a family segregating the splice site mutation c.2189+1G>T in the tyrosine kinase receptor gene MERTK. METHODS: Five affected children of a consanguineous Moroccan family were investigated by ophthalmic examinations, including fundus photography, autofluorescence (FAF) imaging, optical coherence tomography (OCT), psychophysical and electrophysiological methods. RESULTS: Affected children were between 5 and 19 years of age, allowing an estimation of disease progression. Electroretinography demonstrated loss of scotopic and photopic function in the first decade of life. Younger siblings showed drusen-like deposits with focal relatively increased FAF in the macular area. With increasing age, a yellowish lesion with relatively increased FAF and subsequent macular atrophy developed. Visual acuity deteriorated with age and ranged between 20/50 in the best eye of the youngest affected and 20/400 in the worst eye of the oldest affected sibling. Spectral-domain OCT revealed debris-like material in the subneurosensory space. CONCLUSION: The splice site mutation c.2189+1G>T in MERTK causes rod-cone dystrophy with a distinct macular phenotype. The debris in the subneurosensory space resembles that in the Royal College of Surgeons (RCS) rat being the mertk animal model. Patients might therefore benefit from advances in gene therapy that were previously achieved in the RCS rat.

Macular full-thickness and lamellar holes in association with type 2 idiopathic macular telangiectasia.

PURPOSE: To describe patients with full-thickness macular holes (FTMHs) and lamellar macular holes (LMHs) in association with type 2 idiopathic macular telangiectasia (type 2 IMT). METHODS: Six patients with either FTMH or LMH and type 2 IMT were evaluated by means of optical coherence tomography (OCT) imaging, funduscopy, and fluorescein angiography. RESULTS: The age of the examined patients ranged from 57 to 70 years (mean 62.5+/-5.2), and best-corrected visual acuity of the affected eyes ranged from 20/50 to 20/200 (mean 20/100). All eyes showed macular abnormalities typical for nonproliferative type 2 IMT except for one eye with a proliferative disease stage. Three patients had an FTMH, one presenting with bilateral FTMH, and three had an LMH on OCT. In all cases of FTMH, the macular holes did not have elevated margins. Surgery was performed in two patients with a FTHM without subsequent functional improvement. CONCLUSIONS: The altered foveal anatomy with progressive atrophic changes within the neurosensory retina in type 2 IMT may predispose to the development of FTMH and LMH. Type 2 IMT should be considered in the differential diagnosis in patients presenting with macular holes. The association between the two may reflect alternative pathogenetic mechanisms in the development of macular holes.

Discrete arcs of increased fundus autofluorescence in retinal dystrophies and functional correlate on microperimetry.

PURPOSE: To describe the occurrence of discrete arcs of increased fundus autofluorescence (FAF) associated with various retinal dystrophies and to assess their functional significance by fundus-controlled microperimetry. METHODS: Seven patients, three with pigmented paravenous retinochoroidal atrophy (PPRCA), one with sector retinitis pigmentosa (RP), one with typical RP, and two with macular dystrophy were assessed by retinal imaging including FAF imaging. Serial images were obtained within a review period of 6 and 10 years in a patient with PPRCA and macular dystrophy, respectively. Fundus-controlled microperimetry was performed in eight eyes of five patients to determine light increment sensitivity. RESULTS: A discrete arched line of increased FAF was observed without obvious correlate on fundus biomicroscopy. The orientation of this line differed from ring shape in RP and macular dystrophy, a semi-circle structure in sector RP to crescent shape with tiplike extensions towards branching retinal veins in PPRCA. Longitudinal investigation revealed slight migration of the arc in PPRCA and peripheral extension of the ring diameter in macular dystrophy. Microperimetry revealed that the arc of increased FAF sharply delineated areas of severely impaired retinal sensitivity. CONCLUSIONS: The findings indicate that arcs of increased FAF in PPRCA and other retinal dystrophies demarcate areas of impaired retinal function and may migrate over time. FAF imaging may therefore reveal the exact extent of neurosensory dysfunction that may exceed the dimensions anticipated by conventional examinations.