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ZusammenfassungExogen bedingte Retinopathien werden am häufigsten durch externe Stimulanzien, seltener durch unerwünschte Arzneimittelwirkungen systemisch oder intravitreal eingesetzter Medikamente und noch seltener durch Impfungen oder die Einwirkung von Lichtstrahlung verursacht. Die Kenntnis exogener Ursachen und ihre mögliche Symptomatik ist zur Prophylaxe oder zur Früherkennung schädigender Wirkungen und zur adäquaten Beratung der Patienten wichtig.

ZusammenfassungDie Nahinfrarot-Autofluoreszenz (NIA) ist ein nicht-invasives Verfahren zur Untersuchung des retinalen Pigmentepithels (RPE) basierend auf der Darstellung des antioxidativen Schutzfaktors Melanin in den RPE-Zellen. Die NIA verbessert die Früherkennung chorioretinaler Erkrankungen, da bei vielen dieser Erkrankungen mit der NIA Strukturveränderungen des RPE nachweisbar sind, bevor sich in anderen Untersuchungen Krankheitszeichen erkennen lassen.

Exogenously induced retinopathies can be caused by consumation of stimulating substances, systemic or ocular medications, vaccinations, light or irradiation. Some of the effects are transient, whereas other effects induce irreversible toxic reactions. Retinal damage may develop either acutely with obvious relation to the damaging cause, but often may take a long duration of repeated use of a substance or medication. External stimulants (e.g. nicotine, alcohol, poppers, methanol) are the most frequent cause of exogenously induced retinal damage. Side effects from systemic drugs (e.g. hydroxychloroquine, ethambutol, MEK-, ERK-, FLT3-, checkpoint inhibitors, didanosin, pentosanpolysulfat sodium) or intravitreally applied drugs (e.g. antibiotics, VEGF-inhibitors) are less frequent. Ocular side effects associated with vaccinations are rare. Ambient light sources induce no damaging effects on the retina. Incorrect use of technical or medical light sources (e.g. laser pointers) without adherence to safety recommendations or unshielded observation of the sun might induce permanent retinal damage. Local or external irradiation might induce retinal vascular damage resulting in radiation retinopathy.

Near-infrared autofluorescence (NIA) is a non-invasive retinal imaging technique for examination of the retinal pigment epithelium (RPE) based on the autofluorescence of melanin. Melanin has several functions within the RPE cells, in one of them it serves as a protective antioxidative factor within the RPE cells and is involved in the phagocytosis of photoreceptor outer segments. Disorders that affect the photoreceptor-RPE complex result in alterations of RPE cells which are detectable by alterations of NIA. Therefore, NIA allows to detect early alterations in inherited and acquired chorioretinal disorders, frequently prior to ophthalmoscopical visualisation and often prior to alterations in lipofuscin associated fundus autofluorescence (FAF) or optical coherence tomography (OCT). Although NIA and FAF relate to disorders affecting the RPE, findings between both imaging methods differ and the area involved has been demonstrated to be larger in NIA compared to FAF in several disorders (e.g., age-related macular degeneration, retinitis pigmentosa, ABCA4-gene associated Stargardt disease and cone-rod dystrophy, light damage), indicating that NIA detects earlier alterations compared to FAF. In addition, due to the absence of blue-light filtering which limits foveal visualisation in FAF, foveal alterations can be much better detected using NIA. A reduced subfoveal NIA intensity is the earliest sign of autosomal dominant BEST1-associated disease, when FAF and OCT are still normal. In other disorders, a normal subfoveal NIA intensity is associated with good visual acuity. This review summarizes the present knowledge on NIA and demonstrates biomarkers for various chorioretinal disorders.

An early diagnosis, differential diagnosis and possible decision about therapeutic interventions has considerable consequences for the personal and social life of patients affected with inherited retinal dystrophies (IRD). For the ophthalmologist, the clinical heterogeneity interferes with a simple diagnostic approach. The present review suggests a structured clinical approach for the ophthalmological diagnosis of IRD and discusses the relevance of different methods for diagnosis, differential diagnosis and the evaluation of progression. A detailed history should be followed by non-invasive retinal imaging. An early diagnosis prior to visible fundus alterations is facilitated by combining optical coherence tomography, fundus and near-infrared autofluorescence. Spectral reflectance photography, OCT angiography and fluorescence lifetime imaging ophthalmoscopy are helpful in the early diagnosis of specific IRD. If retinal imaging is not sufficient for a diagnosis the multifocal electroretinogram is useful for early diagnosis and full-field electroretinogram for differential diagnosis of IRD. Patients should be referred to specialised IRD-centres for differential diagnosis and possible treatment.Für Patienten mit hereditären Netzhautdystrophien (auf Englisch: inherited retinal dystrophies, IRD) ist die Früherkennung, Differenzialdiagnose und mögliche Therapieentscheidung von erheblicher persönlicher und sozialer Bedeutung. Für den Augenarzt kann dies aufgrund der Heterogenität der Erkrankungen und Verläufe sowie der Seltenheit der IRD eine Herausforderung sein. Die vorliegende Übersicht empfiehlt eine zielorientierte klinisch-ophthalmologische Diagnostik bei Verdacht auf IRD mit einer Bewertung der Relevanz der einzelnen Methoden und ihrer Kombination für Diagnose, Differenzialdiagnose und Beurteilung der Progression im Verlauf. Nach einer umfassenden Anamnese ist initial die Kombination von optischer Kohärenztomografie (OCT), Fundus- und Nahinfrarot-Autofluoreszenz zur Frühdiagnose einer IRD ggf. vor ophthalmoskopisch sichtbaren Läsionen sinnvoll. Spektrale Reflexionsfotografie, OCT-Angiografie und Fluorescence Lifetime Imaging Ophthalmoscopy sind bei einzelnen IRD hilfreich. Erlaubt die retinale Bildgebung keine sichere Diagnose, ist das multifokale Elektroretinogramm zur Frühdiagnose und das Ganzfeld-Elektroretinogramm zur Differenzialdiagnose von IRD geeignet. Eine Vorstellung in Schwerpunktzentren für IRD zur Differenzialdiagnostik und Therapie ist empfehlenswert.

Ziel dieses Artikels sind grundsatzliche Uberlegungen zum Einsatz der spektralen Reflexionsfotografie. Dabei ist jede diagnostische Strategie individuell, und der Auswertungsprozess erlebt mit wachsender Erfahrung und Weiterentwicklung der Technik einen kontinuierlichen Wandel.

In den letzten 20 Jahren konnte sich die optische Koharenztomografie (OCT) zur wichtigsten Technik fur die Diagnostik von Netzhauterkrankungen entwickeln und hat die Makuladiagnostik revolutioniert. Die OCT wurde 1991 erstmals vorgestellt und 1995 in die klinische Diagnostik eingefuhrt. Seither hat die OCT das Verstandnis uber Pathogenese und Verlauf von Netzhauterkrankungen umfassend erweitert. Seit 2007 hat die Spectral-Domain-OCT Technik (SD-OCT; verschiedene Hersteller) die vorherige Time-Domain-OCT-Technik (TD-OCT; Stratus OCT, Carl Zeiss Meditec, Deutschland) aufgrund der deutlich hoheren Bildqualitat infolge von erheblich hoheren Scangeschwindigkeiten und besserer Bildverarbeitung abgelost. Die TD-OCT sollte wegen der deutlich geringeren Auflosung heute nicht mehr verwendet werden.

Die fruhzeitige Diagnose erblicher Netzhaut- oder Sehbahnerkrankungen wird aufgrund unspezifischer Symptome, multipler klinischer Manifestationen und hoher genetischer Heterogenitat oft verzogert. Diese Arbeit stellt eine retrospektive Analyse von Befunden von 4021 Patienten mit erblichen Netzhaut- oder Sehbahnerkrankungen vor, die im Zeitraum von 1986 bis 2014 untersucht worden sind (davon 1171 mehrfach). Neben der klinischen Diagnostik wurde Elektrophysiologie (Ganzfeldelektroretinografie ERG, n = 2088, seit 1986; Elektrookulogramm EOG, n = 381, seit 1986; visuell evozierte Potenziale VEP, n = 595, seit 1986; multifokale Elektoretinografie mfERG, n = 819, seit 1998) oder nicht invasive retinale Bildgebung (Fundusautofluoreszenz FAF, n = 1784, seit 2002), Nah-Infrarot-Autofluoreszenz (NIA, n = 1091, seit 2006), Spectral-Domain-OCT (SD-OCT, n = 848, seit 2008), 3-Wellenlangen-MultiColor-spektrale-Reflexionsfotografie (MC, n = 366, seit 2013) ein- oder mehrmalig durchgefuhrt. Eine molekulargenetische Diagnostik erfolgte zwischen 2006 und 2014 bei 383 Patienten. Auf der Basis dieser Daten kann eine effiziente diagnostische Strategie wie folgt formuliert werden: 1. klinische Diagnostik mit Einschluss von erblichen Netzhaut- und Sehbahnerkrankungen in die Differenzialdiagnose bei Sehstorungen und Gesichtsfeldausfallen unklarer Genese, 2. nicht invasive retinale Bildgebung, 3. elektrophysiologische Funktionsdiagnostik, 4. molekulargenetische Diagnostik bei gezielter Verdachtsdiagnose, 5. spezialarztliche Betreuung, Therapie und Verlaufskontrolle. Die verfugbaren diagnostischen Moglichkeiten haben sich in den letzten Jahren kontinuierlich erweitert. Hervorzuheben ist, dass sich die nicht invasive retinale Bildgebung zur primaren diagnostischen Masnahme entwickelt hat und eine gezielte und nach den modernsten Verfahren ausgerichtete molekulargenetische Diagnostik die Abklarung der genetischen Krankheitsursachen verbessert. Die empfohlene Diagnosestrategie verkurzt die Zeit zur Diagnosefindung fur die Betroffenen, ermoglicht eine fruhzeitige Beratung und Therapie und vermeidet unnotige diagnostische Masnahmen.

Aims To evaluate progression of morphological alterations in chloroquine (CQ) or hydroxychloroquine (HCQ) retinopathy after drug cessation. Methods Eleven female patients (age range at drug cessation 46–78 years; treatment duration 5–20 years) were examined between 2.1 and 7.1 years after drug cessation. In addition to clinical examination, they underwent high-resolution optical coherence tomography (OCT) (spectral domain OCT (SD-OCT); Spectralis OCT, Heidelberg Engineering, Germany), fundus autofluorescence (FAF), near-infrared autofluorescence (NIA; HRA2, Heidelberg Engineering, Germany) and ultra-wide-angle fundus autofluorescence (UW-FAF; Optos 200Tx; Optos PLC, UK). Results Two patients with very limited parafoveal retinopathy did not present with progression within 3 years. In the remaining nine patients, visual acuity deteriorated and progression of retinal degeneration could be documented. FAF, UW-FAF and NIA changes included an increase of affected area or a regional increase or decrease of FAF or NIA intensity. SD-OCT changes included reduction of retinal thickness, an increased area of photoreceptor or retinal pigment epithelial loss, development or increase of cystoid macular oedema (4/9) or development of epiretinal membranes (5/9). Therapy of cystoid macular oedema was of limited benefit. Conclusions CQ retinopathy can progress over a long period of time after drug cessation and may be complicated by cystoid macular oedema, epiretinal membrane formation and peripheral involvement.

Die Behandlungsmoglichkeiten retinaler Erkrankungen haben sich in den letzten Jahren durch die intravitreale operative Medikamentenapplikation (IVOM) von Anti-VEGF-Praparaten (Pegabtanib, Ranibizumab, Bevacizumab, Aflibercept), Kortikoid-Langzeitabgabesystemen (Dexamethason, Fluocinolon-Acetonide) und Ocriplasmin sowie die Spectral-Domain-OCT-Diagnostik erheblich verbessert. Die IVOM ist derzeit weltweit der am haufigsten durchgefuhrte ophthalmochirurgische Eingriff mit kontinuierlich wachsender Tendenz und damit der haufigste chirurgische Eingriff uberhaupt. Dieser Beitrag fasst den aktuellen Wissensstand zu Beginn des Jahres 2013 zusammen.

BACKGROUND: Hereditary retinal dystrophies comprise a heterogeneous group of inherited retinal disorders with variable clinical presentation and multiple associated genes. Clinical diagnosis and differential diagnosis are difficult. The purpose of the current paper is to provide guidelines for an effective diagnostic approach. METHODS: A literature search was carried out and our own data on clinical (n = 3200) and molecular genetic (n = 4050) diagnosis of patients with retinal dystrophies were evaluated. RESULTS: For an early diagnosis it is of importance to include inherited retinal dystrophies in the differential diagnosis of unexplained visual disturbances. The most important clinical test is the full-field electroretinogram (ERG), which allows detection or exclusion of generalised retinal dystrophies. If the full-field ERG is normal, a multifocal ERG will distinguish macular dystrophies. Fundus autofluorescence, near-infrared autofluorescence and high resolution optical coherence tomography improve the early diagnosis because morphological alterations can be detected prior to their ophthalmoscopic visibility. In addition, these non-invasive imaging techniques reveal new phenomena which are important for the differential diagnosis and follow-up of retinal dystrophies as well as for an improved understanding of their pathogenesis. Routine molecular genetic diagnosis is available for an increasing number of retinal dystrophies. A succinct clinical diagnosis is a prerequisite to allow selection of the gene(s) to be analysed. If genetic testing is indicated, a human geneticist should be involved for counselling of the patient and possibly further family members and initiation of the necessary steps for DNA testing. CONCLUSION: The combination of electrophysiological testing, retinal imaging and molecular genetic analysis allows a differentiated diagnosis of inherited retinal dystrophies and an individual counselling of patients. If inherited retinal dystrophies are suspected, a detailed examination in a retinal centre specialised on inherited retinal dystrophies is recommended.

The purpose of this study was to compare near-infrared fundus autofluorescence(NIA, excitation 787 nm, emission800 nm) with fundus autofluorescence (FAF,excitation 488 nm, emission500 nm) in patients with age-related macular degeneration(AMD).Fundus autofluorescence and NIA were obtained using a confocal scanning laser ophthalmoscope (HRA2) in 308 eyes (172 patients) with AMD [age-related maculopathy(n 116), geographic atrophy (n 77), and neovascular AMD (n 115)].Retinal pigment epithelial alterations were detected with FAF and NIA in all eyes and showed a similar lesion size in 81.8%. In age-related maculopathy, spots of increased FAF (87.9%) were more frequent than spots of reduced FAF (26.7%). Spots of increased and reduced NIA were of similar frequency (66.4%). A higher relative intensity of FAF was more frequent (72.4%) than higher relative NIA intensity (16.4%), suggesting that loss of NIA usually precedes loss of FAF. The junctional zone of geographic atrophy presented with increased NIA (19.5%), increased FAF (10.4%), or an increase of both(22.1%). In neovascular AMD, exudative changes were better visualized with FAF (56.5%)compared with NIA (33.9%).Patterns of FAF and NIA indicate different involvement of lipofuscin and melanin in the pathophysiological process and provide further insight into the development of AMD and noninvasive monitoring of future therapeutic interventions.

To compare melanin-related near-infrared fundus autofluorescence (FAF; NIA, excitation 787 nm, emission800 nm) with lipofuscin-related FAF (excitation 488 nm, emission500 nm) in retinitis pigmentosa (RP).Thirty-three consecutive RP patients with different modes of inheritance were diagnosed clinically, with full-field ERG, and if possible with molecular genetic methods. FAF and NIA imaging were performed with a confocal scanning laser ophthalmoscope (Heidelberg Retina Angiograph 2).Rings of increased FAF were present within an area of preserved retinal pigment epithelium (RPE) at the posterior pole (31/33). Rings of increased NIA were located in the same region as rings of increased FAF. In contrast to FAF, NIA showed a precipitous decline of NIA peripheral to the ring. In larger areas of preserved NIA (11/31), pericentral and foveal NIA were of similar intensity with an area of lower NIA in between. In smaller areas of preserved NIA (20/31), NIA was homogeneous from the perifovea to the fovea. In one patient without a ring of increased FAF, NIA distribution was normal. In the remaining patient with severely advanced RP, no residual RPE as well as no FAF and NIA were detectable.Characteristic features for FAF and NIA alterations in a heterogeneous group of RP patients indicate a common pathway of RPE degeneration. Patterns of NIA and FAF indicate different pathophysiologic processes involving melanin and lipofuscin. Combined NIA and FAF imaging will provide further insight into the pathogenesis of RP and non-invasive monitoring of future therapeutic interventions.

Purpose To compare melanin-related near-infrared fundus autofluorescence (NIA; excitation 787 nm, emission > 800 nm) to lipofuscin-related fundus autofluorescence (FAF; excitation 488 nm, emission > 500 nm) in patients with retinal dystrophies associated with ABCA4 gene mutations (ABCA4-RD). Design Observational case series. Methods Sixteen consecutive patients with ABCA4-RD diagnosed in one institution were included. FAF and NIA imaging were performed with a confocal scanning laser ophthalmoscope (Heidelberg Retina Angiograph 2; Heidelberg Engineering, Heidelberg, Germany). The pattern and size of retinal pigment epithelial (RPE) alterations detected with FAF and NIA were evaluated. Results FAF and NIA alterations were detected in all patients. In 7 of 16 patients, the alterations progressed beyond the vascular arcades, and in 9 of 16, they were confined to the macula. Spots of increased NIA (4/16) were less frequent compared with spots of increased FAF (15/16). Confluent patches of reduced NIA were frequent (12/16), and severely reduced NIA was observed in 3 cases. Areas with reduced NIA corresponded to either increased or reduced FAF. Preservation of subfoveal FAF or NIA corresponded to visual acuity ≥ 0.4. Abnormalities detected with NIA were more extensive or more severe compared to FAF in 15 of 16 patients. Conclusion Patterns of FAF and NIA indicate different involvement of lipofuscin and melanin and their derivates in the pathophysiologic process of ABCA4-RD. NIA imaging provides a noninvasive in vivo visualization of RPE abnormalities that may precede FAF alterations during the degenerative process. Combined FAF and NIA imaging will provide further insight in the development of ABCA4-RD and could help to monitor future therapeutic interventions.