Clinical characteristics of gyrate atrophy compared with a gyrate atrophy-like retinal phenotype.

INTRODUCTION: Gyrate atrophy (GA) is a rare retinal dystrophy due to biallelic pathogenic variants in the ornithine aminotransferase (OAT) gene, causing a 10-fold increase in plasma ornithine levels. It is characterized by circular patches of chorioretinal atrophy. However, a GA-like retinal phenotype (GALRP) without elevated ornithine levels has also been reported. The aim of this study is to compare the clinical characteristics of GA and GALRP and to identify possible discriminators. METHODS: A multicenter, retrospective chart review was performed at three German referral centres on patient records between 01/01/2009 and 31/12/2021. Records were screened for patients affected by GA or GALRP. Only patients with examination results for plasma ornithine levels and / or genetic testing of the OAT gene were included. Further clinical data was gathered where available. RESULTS: Ten patients (5 female) were included in the analysis. Three suffered from GA, while seven had a GALRP. Mean age (± SD) at onset of symptoms was 12.3 (± 3.5) years for GA compared with 46.7 (± 14.0) years for GALRP patients (p = 0.002). Mean degree of myopia was higher in GA (-8.0 dpt. ± 3.6) compared to GALRP patients (-3.8 dpt. ± 4.8, p = 0.04). Interestingly, all GA patients showed macular oedema, while only one GALRP patient did. Only one patient with GALRP had a positive family history, while two were immunosuppressed. DISCUSSION: Age of onset, refraction and presence of macular cystoid cavities appear to be discriminators between GA and GALRP. GALRP may encompass both genetic and non-genetic subtypes.

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.

[Prospective noninterventional BLUE SKY study evaluating the efficacy of brolucizumab in treatment-naïve and previously treated patients with neovascular AMD]. / Prospektive nichtinterventionelle BLUE SKY-Studie zur Beurteilung der Wirksamkeit von Brolucizumab bei unbehandelten und vorbehandelten Patienten mit neovaskulärer AMD.

Intravitreal injection of anti-vascular endothelial growth factor (VEGF) is the standard treatment for patients with neovascular age-related macular degeneration (nAMD). In addition to the approved substances ranibizumab (Lucentis®, Novartis) and aflibercept (Eylea®, Bayer), bevacizumab (Avastin®, Roche) is also available. Furthermore, brolucizumab (Beovu®, Novartis) has been approved and has been available in Germany since April 2020. The multicenter, noninterventional prospective BLUE SKY study investigates brolucizumab treatment with different schemes in 600 treatment-naive and pretreated nAMD patients in routine clinical practice over a 24-month period. Besides general patient data, visual acuity and treatment data will be documented. Fluorescein angiography, fundus photography, spectral domain optical coherence tomography and swept-source optical coherence tomography angiography will be performed and analyzed by reading centers. The focus of the analysis will be on the intraretinal and subretinal fluid distribution as well as morphological MNV changes and injection frequency. Also, safety and adverse drug effects of brolucizumab, with a specific focus on inflammatory complications, particularly retinal (occlusive) vasculitis will be evaluated.

[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.

[Long-term effects of anti-VEGF therapy for retinopathy of prematurity]. / Langzeiteffekte der Anti-VEGF-Therapie bei Frühgeborenenretinopathie.

BACKGROUND: Intravitreal anti-VEGF therapy is a highly efficacious new treatment option for retinopathy of prematurity (ROP) with significant advantages over conventional therapy using retinal laser coagulation in selected cases. With growing experience in the clinical application over the last years, data about the potential long-term effects of this therapeutic approach are increasingly becoming available, such as those related to ROP-associated myopia, neurodevelopment and late recurrences of ROP. Knowledge of these effects is of direct relevance for the clinical management of affected children. METHODS: The article is based on a literature review of the covered topics. RESULTS: In addition to its therapeutic effect on retinal pathology, anti-VEGF therapy in ROP can also reduce ROP-associated myopia, most likely due to a normalization of anterior segment development. As the unresolved question of potential negative effects of bevacizumab on neurodevelopment remains of concern, the use of alternative treatment options, such as ranibizumab or laser coagulation should be considered. Treatment-requiring recurrences of ROP following anti-VEGF therapy have been reported as late as 69 weeks postmenstrual age, indicating that long-term frequent ophthalmological follow-up examinations are required. CONCLUSION: Long-term effects of anti-VEGF therapy in ROP differ significantly from alternative treatment options such as laser coagulation. These differences are of relevance for the choice of treatment modality and the follow-up regimen of treated children.

[Screening for retinopathy of prematurity: Trends over the past 5 years in two German university hospitals]. / Frühgeborenenretinopathie-Screening: Trends über die vergangenen 5 Jahre an zwei deutschen Universitätskliniken.

BACKGROUND: The number of preterm births in Germany has been increasing continuously over the past decades. Retinopathy of prematurity (ROP) is a major complication of preterm birth and one of the leading causes of blindness in children. OBJECTIVES: This study analyzes the development of the incidence of ROP over the past 5 years at two German university hospitals, utilizing data from ROP screening examinations. MATERIAL AND METHODS: We assessed all children born in the years 2012-2016 who were included in the ROP screening program at two German university hospitals according to the criteria of the German ROP screening guidelines. Parameters such as gestational age, birth weight, ROP stage and zone, and need for therapeutic intervention were assessed. RESULTS: We analyzed the data of 863 children who had undergone a total of 4117 screening examinations. The number of children included in the screening program per study year increased continuously over the study period by a total of 43.1% (137 in 2012, 196 in 2016). Likewise, the number of screening examinations per year increased by 58.4% (608 in 2012, 963 in 2016). Overall, 27.5% of screened infants were diagnosed with ROP of any stage and 2.5% required treatment for ROP. The number of children diagnosed with ROP of any stage per year increased by 100.0% (32 in 2012, 64 in 2016). Mean gestational age (29.0 ± 3.0 weeks) and mean birth weight (1192 ± 513 g) remained stable over the study period. CONCLUSION: Screening data for ROP from two German university hospitals demonstrates a significant increase in both the number of screened infants and the number of infants affected by ROP over the past 5 years.

[Optical coherence tomography angiography (OCT­A) in rats]. / Optische-Kohärenztomographie-Angiographie (OCT­A) bei Ratten.

PURPOSE: Optical coherence tomography angiography (OCT­A) allows for the non-invasive, three-dimensional visualization of retinal and chorioidal vascular structures. In this study, this new imaging modality was evaluated in rats. METHODS: In vivo imaging in Dark Agouti rats was performed using confocal scanning laser ophthalmoscopy (cSLO) and OCT­A (Spectralis prototype, Heidelberg Engineering) after adjusting the length of the reference arm. The OCT­A en-face images were compared to conventional fluorescein angiography cSLO images. The histological examination allowed for correlation of retinal and chorioidal plexus. RESULTS: While the diagnostic device was developed for use in humans, OCT­A and cSLO imaging can be applied in rodents after only minor hardware modifications. High-resolution and contrast-enhanced images enable a depth-selective visualization of the three retinal plexus and the inner and outer chorioidal vascular networks. In comparison to fluorescein angiography (FA), OCT­A is characterized by higher resolution and more accurate three-dimensional localization of vascular structures, particularly in deep layers. A current limitation includes the relatively small area imaged by OCT­A. DISCUSSION: The recently developed OCT­A imaging technology also allows for three-dimensional detection of retinal and chorioidal vascular changes in vivo without dye injection in rodents. OCT may potentially replace invasive FA for specific questions and will be useful in animal models for research of retinal and chorioidal angiogenic processes physiologically and during pharmacological interventions.

["Iodine allergy" : A medical myth with risks for the ophthalmological patient]. / "Iodallergie" : Ein medizinischer Mythos mit Risiken für den ophthalmologischen Patienten.

BACKGROUND: Preoperative disinfection with povidone-iodine results in a significant reduction of the risk for postoperative endophthalmitis and secondary irreversible vision loss in intraocular surgeries and intravitreal injections. Nevertheless, this important measure is often omitted if so-called "iodine allergy" is suspected. We analyze the physiological and allergological basis for the construct of "iodine allergy". METHODS: This article is based on a selective literature review using the search term "allergy" in combination with "iodine", "povidone", "indocyanine green", or "seafood". RESULTS: Iodine is a chemical element and an essential component of the human body. Scientific proof for the existence of an antibody-mediated allergic reaction (type I reaction) and in particular an immunoglobulin (Ig) E­mediated anaphylaxis against iodine is lacking. Chemical irritations and contact allergies (type IV reaction) induced by iodine-containing disinfectants are not antibody-mediated and do not cause anaphylaxis (type I reaction). The uncommon antibody-mediated allergies against iodine-containing disinfectants, fluorescent dyes, radiocontrast media, or seafood are not directed against the contained iodine itself but against other components of the respective formulation. Thus, allergic cross-reactivities between these different substance groups are not to be expected. CONCLUSION: So-called "iodine allergy" is a medical myth lacking a scientific basis and should not result in increased patient risks due to omitted preoperative disinfection.

[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.

[Technical principles of OCT angiography]. / Technische Grundlagen der OCT-Angiographie.

BACKGROUND: Optical coherence tomography angiography (OCT-A) is a new diagnostic non-invasive method by which the vascular structures of the retina and choroid can be visualized three-dimensionally without need for using fluorescence dyes. The technology of OCT-A is an advancement of the OCT. By means of more powerful software and hardware used for OCT-A not only morphological but also retinal and choroidal vascular perfusion analyses can be performed. In this article, the principles and applications of OCT-A are discussed and compared to other non-invasive diagnostic devices for visualization of the retinal and choroidal blood circulation. METHODS: This article is based on a selective literature review and analyses of own data. RESULTS: The advantages of OCT-A include easy application without the need for mydriasis or intravenous injection of fluorescence dyes and also the exact three-dimensional localization of vascular changes. In the case of retinal pathologies there is a considerable difference between software-assisted automatic segmentation and the real architecture of the retina, which must be taken into consideration in the clinical interpretation. CONCLUSION: Of all noninvasive devices for visualization of the retinal and choroidal circulation, OCT-A is the only one which can already be implemented into the clinical routine. With this novel imaging device retinal and choroidal alterations can be visualized in a depth- selective manner and without masking affects, such as pooling or staining phenomena.

[Pharmacokinetics of intravitreally administered VEGF inhibitors]. / Pharmakokinetik intravitreal applizierter VEGF-Inhibitoren.

BACKGROUND: In addition to topical, periocular and systemic administration, intravitreal injection has been established in recent years as an additional standard procedure for ophthalmological drug delivery. This route of administration is now most frequently used for the therapy of retinal diseases with vascular endothelial growth factor (VEGF) inhibitors. MATERIAL AND METHODS: A selective literature review and an analysis of own research data were carried out. RESULTS: Intravitreal administration achieves high drug concentrations in the target tissue while minimizing systemic drug exposure. Depending on properties such as molecular weight and binding capacity to the neonatal Fc receptor, intravitreally applied VEGF inhibitors can exhibit relevant differences in intraocular and systemic pharmacokinetics. Moreover, the pharmacokinetics can be affected by properties of the individual eye, such as ocular volume, vitreous liquefaction, and prior vitrectomy. CONCLUSIONS: Pharmacokinetics of intravitreally administered drugs determine both the duration of ocular effect and the degree of systemic exposure and are thus of clinical relevance with regard to the reinjection strategy and systemic safety.

[Current therapeutic options in retinopathy of prematurity]. / Aktuelle Therapieoptionen bei Frühgeborenenretinopathie.

Retinopathy of prematurity is one of only few potentially blinding retinal diseases of infancy amenable to prevention of visual loss by appropriate and timely therapeutic measures. Retinal ablative therapies, such as laser coagulation eliminate the disease-causing secretion of vascular endothelial growth factor (VEGF) by the avascular peripheral retina. Blockage of VEGF activity by intravitreal administration of VEGF-inhibitory drugs has likewise proven effective in recent clinical studies. Advanced stages of the disease may require surgical intervention. Knowledge of indications and techniques of the different currently available treatment options is crucial to ensure an optimal visual outcome for the affected children.

[Retinopathy of prematurity - pathophysiologic mechanisms and new treatment options]. / Frühgeborenenretinopathie - Pathophysiologische Grundlagen und aktuelle Behandlungsoptionen.

Retinopathy of prematurity (ROP), like other angioproliferative retinal disorders, has witnessed the advent of anti-VEGF therapy in clinical practice. The first report from the BEAT-ROP study published in 2011 represents the first comparison of anti-VEGF therapy versus conventional laser treatment in a randomised controlled trial. This review article investigates these novel aspects of ROP therapy from a pathophysiological angle and delineates the stages of ROP in which anti-VEGF treatment appears as a reasonable option. Furthermore, the novel chances of anti-VEGF therapy are being weighed against some still unanswered questions and novel study concepts are being presented.

[Unilateral blurred vision associated with combined macular and papillary edema: a 34-year-old male patient]. / Einseitiges Verschwommensehen assoziiert mit kombiniertem Makula- und Papillenödem: Fall eines 34-jährigen Patienten.

We present clinical images of a case of Leber's idiopathic stellate neuroretinitis (LISN). A 34-year-old male presented with acute-onset unilateral blurred vision for 5 days. Clinical examination revealed sectorial papillary edema and extensive macular edema in the affected eye. Using optical coherence tomography we detected intraretinal fluid in the outer retinal layers and subretinal fluid under the fovea. Seven days later, the macular edema was completely resolved, and disseminated retinal exudates had appeared, resembling a macular star figure. No underlying systemic disease was identified. Follow-up examination after 3 months demonstrated almost complete spontaneous resolution of fundus changes and near-normalization of visual acuity.

[Juvenile neuronal ceroid lipofuscinosis. Ophthalmologic findings and differential diagnosis]. / Juvenile neuronale Zeroidlipofuszinose. Ophthalmologische Diagnostik und Differenzialdiagnose.

Neuronal ceroid lipofuscinoses (NCL) are a heterogeneous group of neurodegenerative diseases with mostly autosomal recessive inheritance whose common feature is the intralysosomal accumulation of ceroid lipofuscin. With varying manifestation ages the diseases result in cognitive and motor deterioration, epilepsy, diffuse retinal degeneration, and eventually death. Juvenile ceroid lipofuscinosis (JNCL, CLN3, Batten disease) has the distinctive feature that the ophthalmologic symptoms precede the neurologic symptoms by several years, and thus the ophthalmologist plays a central role in early diagnosis. Important clinical signs of JNCL include bull's eye maculopathy, severely reduced Ganzfeld ERG already at initial presentation, and unusually rapid progression of the functional decline. If JNCL is clinically suspected the diagnosis can be made by means of a standard blood smear and confirmed by genetic detection of the mutation. Although causal therapeutic options are currently only in the developmental stage, early diagnosis by the ophthalmologist is of utmost importance to allow for medical and educational support of the affected child and for adequate counseling of the parents.