The landscape of submicroscopic structural variants at the OPN1LW/OPN1MW gene cluster on Xq28 underlying blue cone monochromacy.

Blue cone monochromacy (BCM) is an X-linked retinal disorder characterized by low vision, photoaversion, and poor color discrimination. BCM is due to the lack of long-wavelength-sensitive and middle-wavelength-sensitive cone photoreceptor function and caused by mutations in the OPN1LW/OPN1MW gene cluster on Xq28. Here, we investigated the prevalence and the landscape of submicroscopic structural variants (SVs) at single-base resolution in BCM patients. We found that about one-third (n = 73) of the 213 molecularly confirmed BCM families carry an SV, most commonly deletions restricted to the OPN1LW/OPN1MW gene cluster. The structure and precise breakpoints of the SVs were resolved in all but one of the 73 families. Twenty-two families-all from the United States-showed the same SV, and we confirmed a common ancestry of this mutation. In total, 42 distinct SVs were identified, including 40 previously unreported SVs, thereby quadrupling the number of precisely mapped SVs underlying BCM. Notably, there was no "region of overlap" among these SVs. However, 90% of SVs encompass the upstream locus control region, an essential enhancer element. Its minimal functional extent based on deletion mapping in patients was refined to 358 bp. Breakpoint analyses suggest diverse mechanisms underlying SV formation as well as in one case the gene conversion-based exchange of a 142-bp deletion between opsin genes. Using parsimonious assumptions, we reconstructed the composition and copy number of the OPN1LW/OPN1MW gene cluster prior to the mutation event and found evidence that large gene arrays may be predisposed to the occurrence of SVs at this locus.

[Training of Medical Assistants in Ophthalmology: Survey of a Sample of Large Ophthalmic Centers]. / Ausbildung von MFA in der Ophthalmologie. Ergebnisse einer Stichprobe von großen augenmedizinischen Zentren.

The shortage of specialists in SHI-accredited medical care is increasingly affecting medical assistants (MFA) in medical practices and Medical Care Center (MVZ). Training can mitigate the associated problems in the future, but currently only 42% of practices provide training. A survey of a sample of large ophthalmic centers was conducted to test the hypothesis that larger practices and MVZs provide disproportionate training. In addition, an interaction between ownership (physician-owned (äE); third-party owned (F)) and training engagement was evaluated. In a questionnaire-based complete survey (2022) of large ophthalmic centers of different ownerships organized in a network, the training rate by main operating site (HBS), the number of MFA trainees (MFA-A) per HBS, staffing problems and planned change in training commitment were collected. The distribution measures of the quantitative data were analyzed overall and separately by sponsoring organization and tested for significance.Results were compared to data from a representative survey (2020/2021) of all practices and MVZs. In order to determine the proportion of all ophthalmic MFA-A accounted for by the sample, their total number was determined in an extrapolation. The training rate of the total of 100 HBS of the 14 surveyed centers (11 äE, 3 F) of the sample was 82% (äE: 93%, F: 79%), which was higher than the representative survey (41%). In the sample, there were on average 5.9 MFA-A per HBS (äE: 5.6, F: 7.1), in the comparative survey 1.5. 50% of the centers in the sample reported staffing problems, 25% wanted to expand their training commitment; the comparative values of the representative survey were 11% for both parameters. Stratified by sponsorship, neither training rate nor MFA-A per HBS showed significant differences. According to projections, there were nearly 1,966 MFA-A working in ophthalmology in 2021, of which 19.5% were at centers in the study population. Of all the MFA-A in the sample, 71% were at the significantly larger centers by number of HBS owned by third-party. The survey confirms the positive correlation between the size of practices and MVZ and commitment to training. There are no significant differences according to the ownership of organization.

DNAJC30 disease-causing gene variants in a large Central European cohort of patients with suspected Leber's hereditary optic neuropathy and optic atrophy.

BACKGROUND: Leber's hereditary optic neuropathy (LHON) has been considered a prototypical mitochondriopathy and a textbook example for maternal inheritance linked to certain disease-causing variants in the mitochondrial genome. Recently, an autosomal recessive form of LHON (arLHON) has been described, caused by disease-causing variants in the nuclear encoded gene DNAJC30. METHODS AND RESULTS: In this study, we screened the DNAJC30 gene in a large Central European cohort of patients with a clinical diagnosis of LHON or other autosomal inherited optic atrophies (OA). We identified likely pathogenic variants in 35/1202 patients, corresponding to a detection rate of 2.9%. The previously described missense variant c.152A>G;p.(Tyr51Cys) accounts for 90% of disease-associated alleles in our cohort and we confirmed a strong founder effect. Furthermore, we identified two novel pathogenic variants in DNAJC30: the nonsense variant c.610G>T;p.(Glu204*) and the in-frame deletion c.230_232del;p.(His77del). Clinical investigation of the patients with arLHON revealed a younger age of onset, a more frequent bilateral onset and an increased clinically relevant recovery compared with LHON associated with disease-causing variants in the mitochondrial DNA. CONCLUSION: This study expands previous findings on arLHON and emphasises the importance of DNAJC30 in the genetic diagnostics of LHON and OA in European patients.

[Less Frequent Vascular Disorders of the Retina - Part 1]. / Seltene vaskuläre Erkrankungen der Netzhaut ­ Teil 1.

This review provides an overview of retinal vascular disorders that are less frequent in Germany and Europe compared to diabetic retinopathy and retinal venous or arterial occlusive disorders. The knowledge of these disorders is important for the differential diagnosis of retinal vascular disorders as well as potentially associated systemic disorders. In the current part one epidemiology, pathophysiology, clinical presentation, and therapy are discussed for hypertensive retinochoroidopathy, ocular ischemic syndrome, retinal alterations in sickle cell disease, Eales disease, radiation retinopathy, peripheral exudative hemorrhagic chorioretinopathy, and retinal disorders associated with pregnancy.

Comprehensive variant spectrum of the CNGA3 gene in patients affected by achromatopsia.

Achromatopsia (ACHM) is a congenital cone photoreceptor disorder characterized by impaired color discrimination, low visual acuity, photosensitivity, and nystagmus. To date, six genes have been associated with ACHM (CNGA3, CNGB3, GNAT2, PDE6C, PDE6H, and ATF6), the majority of these being implicated in the cone phototransduction cascade. CNGA3 encodes the CNGA3 subunit of the cyclic nucleotide-gated ion channel in cone photoreceptors and is one of the major disease-associated genes for ACHM. Herein, we provide a comprehensive overview of the CNGA3 variant spectrum in a cohort of 1060 genetically confirmed ACHM patients, 385 (36.3%) of these carrying "likely disease-causing" variants in CNGA3. Compiling our own genetic data with those reported in the literature and in public databases, we further extend the CNGA3 variant spectrum to a total of 316 variants, 244 of which we interpreted as "likely disease-causing" according to ACMG/AMP criteria. We report 48 novel "likely disease-causing" variants, 24 of which are missense substitutions underlining the predominant role of this mutation class in the CNGA3 variant spectrum. In addition, we provide extensive in silico analyses and summarize reported functional data of previously analyzed missense, nonsense and splicing variants to further advance the pathogenicity assessment of the identified variants.

Optical coherence tomography angiography (OCT-A) in retinitis pigmentosa and macular dystrophy patients: a retrospective study.

PURPOSE: To evaluate macular vascular abnormalities in patients with macular dystrophies (MD) and retinitis pigmentosa (RP) through application of optical coherence tomography angiography (OCT-A). METHODS: In this retrospective study, patients with MD and RP were examined by OCT-A and compared to healthy individuals. OCT-A images were analyzed regarding the diameter and surface area of the foveal avascular zone (FAZ) as well as flow (FL) in different retinal layers (superficial vascular complex (SVC), intermediate capillary complex (ICP), deep capillary complex (DCP), choriocapillaris (CC), and choroid (CD)). RESULTS: Twenty-one patients with MD, 21 patients with RP without macular edema (RPnE), 8 patients with RP with edema (RPwE), and 41 healthy individuals were enrolled. The group of MD and RPnE patients showed none or only minor changes in FAZ. In RPwE patients, the FAZ was significantly smaller in vertical and horizontal measurements and surface area in SVC, whereas it was markedly enlarged in ICP. FL was significantly reduced compared to healthy individuals by an average of 13.2% in CD, 14.2% in CC, and 8.4% in DCP in all patient groups. In ICP, the reduction was 9.2% for RPnE and 12.7% for RPwE patients. The SVC showed reduced FL in the MD (8.1%) and RPnE (10.3%) group. CONCLUSIONS: OCT-A is a valuable tool to examine retinal vascular abnormalities in patients with MD and RP. OCT-A revealed a reduced flow in various retinal layers in MD, RPnE, and RPwE. Alterations of the FAZ were less distinct in these groups which add to the variation reported previously.

Investigation of Structural Alterations in Inherited Retinal Diseases: A Quantitative SD-OCT-Analysis of Retinal Layer Thicknesses in Light of Underlying Genetic Mutations.

Inherited retinal diseases can result from various genetic defects and are one of the leading causes for blindness in the working-age population. The present study aims to provide a comprehensive description of changes in retinal structure associated with phenotypic disease entities and underlying genetic mutations. Full macular spectral domain optical coherence tomography scans were obtained and manually segmented in 16 patients with retinitis pigmentosa, 7 patients with cone−rod dystrophy, and 7 patients with Stargardt disease, as well as 23 age- and sex-matched controls without retinal disease, to assess retinal layer thicknesses. As indicated by generalized least squares models, all IRDs were associated with retinal thinning (p < 0.001), especially of the outer nuclear layer (ONL, p < 0.001). Except for the retinal nerve fiber layer, such thinning was associated with a reduced visual acuity (p < 0.001). These advances in our understanding of ultrastructural retinal changes are important for the development of gene-, cell-, and optogenetic therapy. Longitudinal studies are warranted to describe the temporal component of those changes.

Digital 3D "Heads-up" Cataract Surgery: Safety Profile and Comparison with the Conventional Microscope System. / Digitale 3-D-Monitor-"Heads-up"-Kataraktchirurgie: Sicherheitsprofil und Vergleich zum konventionellen Mikroskopsystem.

PURPOSE: The aim of this study was to compare the complication rates between surgery performed using digital heads-up 3D system (3D group) and a conventional binocular microscope-based system (BM group) in a large series of cataract operations performed by the same surgeon. METHODS: This retrospective analysis included a consecutive series of 2,000 cataract operations. The 3D group included n = 1,000 operations performed immediately following the introduction of a 3D system (Alcon Ngenuity). For comparison, the last n = 1,000 operations performed with a binocular microscope were included in the BM group. The 3D system was adapted to the existing microscope so that the microscope optics remained unchanged. The In both groups, the surgical techniques used were either phacoemulsification or femtosecond laser cataract surgery. Complications were recorded and analyzed retrospectively. RESULTS: The proportion of femto-laser cataract operations was 19.8% in the 3D group and 18.6% in the BM group. Capsule rupture occurred in 10 eyes (3D: n = 4 (0.4%), anterior vitrectomy: n = 2, pars plana vitrectomy: n = 1; BM: n = 6 cases (0.6%), anterior vitrectomy: n = 4, pars plana vitrectomy: n = 1). A short-term iris prolapse occurred in 3 eyes (3D: n = 2, BM: n = 1). Zonulolysis occurred in 2 eyes (3D: n = 1, BM: n = 1). Overall, there was no statistically significant difference between the two groups (p > 0.5). There was no significant increase in the duration of surgery following the switch to the 3D technique. CONCLUSION: In a large series of 2000 eyes, there was no significant difference between 3D and BM surgery in terms of the safety profile during cataract surgery. 3D surgery can, therefore, be used for cataract operations without additional risk.

[Near-infrared Fundus Autofluorescence: Clinical Application and Diagnostic Relevance]. / Nahinfrarot-Autofluoreszenz: klinische Anwendung und diagnostische Relevanz.

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.

[Exogenously induced retinopathies]. / Exogen bedingte Retinopathien.

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.

[Retinopathy of Prematurity - Update on Classification, Screening, and Therapy]. / Frühgeborenenretinopathie.

Retinopathy of prematurity (ROP) is a leading cause of preventable childhood blindness. This proliferative retinal vascular disease affects only prematurely born infants. Major risk factors include low gestational age and prolonged postnatal oxygen supplementation. ROP screening allows for timely identification of treatment-requiring infants and thus significantly reduces the risk of severe visual impairment and blindness from ROP. Current treatment options comprise retinal laser coagulation and intravitreal anti-vascular endothelial growth factor (VEGF) therapy. We provide a review of scientific data and current treatment recommendations, with special attention to the updated German guideline on ROP screening, the statement of the German ophthalmological societies on anti-VEGF therapy of ROP, and the new third edition of the International Classification of Retinopathy of Prematurity (ICROP3).

Treatment contentment and preference of patients undergoing intravitreal anti-VEGF therapy.

PURPOSE: The aim of this study is to investigate patients´ treatment preference between the pro re nata (PRN) and treat and extend (T&E) regimens and their feelings and contentment undergoing intravitreal injections (IVI) with anti-vascular endothelial growth factor (anti-VEGF) agents. METHODS: Six months after the switch of the treatment regimen from PRN to T&E, answers of a 16-item questionnaire of 105 patients under IVI therapy regarding age, sex and treatment preference (T&E or PRN regimen), as well as burden and anxiety resulting from therapy, were evaluated. Analysis of associations between answers of the questionnaire was executed using Pearson's Chi2 test and Mann-Whitney U test. P values ≤ 0.05 were considered statistically significant. RESULTS: Nearly all patients (90.5%) felt well informed about disease and therapy. Comparing treatment regimen, 13.7% thought PRN was better and 23.3% felt T&E was better. The majority considered PRN and T&E to be equal (60.3%). No significant association between treatment regimen and age (p = 0.15), gender (p = 0.35) and duration of IVI therapy (p = 0.42) was seen. The examination results are associated with fear in the majority of patients (53.3%). Fear about the IVI was indicated by 47.6% of individuals and was significantly associated with pain during treatment (p = 0.0003), pain after treatment (p = 0.004) and fear about unfavourable examination results regarding disease activity (p = 7.94 × 10-7). CONCLUSIONS: Most patients are satisfied with the IVI therapy and the treatment regimen. Fear of the IVI and particularly of unfavourable examination results demonstrate the high treatment burden for patients undergoing anti-VEGF therapy. These aspects should be taken into account by healthcare professionals.

Autosomal Dominant Gyrate Atrophy-Like Choroidal Dystrophy Revisited: 45 Years Follow-Up and Association with a Novel C1QTNF5 Missense Variant.

We present a long-term follow-up in autosomal dominant gyrate atrophy-like choroidal dystrophy (adGALCD) and propose a possible genotype/phenotype correlation. Ophthalmic examination of six patients from two families revealed confluent areas of choroidal atrophy resembling gyrate atrophy, starting in the second decade of life. Progression continued centrally, reaching the fovea at about 60 years of age. Subretinal deposits, retinal pigmentation or choroidal neovascularization as seen in late-onset retinal degeneration (LORD) were not observed. Whole genome sequencing revealed a novel missense variant in the C1QTNF5 gene (p.(Q180E)) which was found in heterozygous state in all affected subjects. Haplotype analysis showed that this variant found in both families is identical by descent. Three-dimensional modeling of the possible supramolecular assemblies of C1QTNF5 revealed that the p.(Q180E) variant led to the destabilization of protein tertiary and quaternary structures, affecting both the stability of the single protomer and the entire globular head, thus exerting detrimental effects on the formation of C1QTNF5 trimeric globular domains and their interaction. In conclusion, we propose that the p.(Q180E) variant causes a specific phenotype, adGALCD, that differs in multiple clinical aspects from LORD. Disruption of optimal cell-adhesion mechanisms is expected when analyzing the effects of the point mutation at the protein level.

Deep-intronic variants in CNGB3 cause achromatopsia by pseudoexon activation.

Our comprehensive cohort of 1100 unrelated achromatopsia (ACHM) patients comprises a considerable number of cases (~5%) harboring only a single pathogenic variant in the major ACHM gene CNGB3. We sequenced the entire CNGB3 locus in 33 of these patients to find a second variant which eventually explained the patients' phenotype. Forty-seven intronic CNGB3 variants were identified in 28 subjects after a filtering step based on frequency and the exclusion of variants found in cis with pathogenic alleles. In a second step, in silico prediction tools were used to filter out those variants with little odds of being deleterious. This left three variants that were analyzed using heterologous splicing assays. Variant c.1663-1205G>A, found in 14 subjects, and variant c.1663-2137C>T, found in two subjects, were indeed shown to exert a splicing defect by causing pseudoexon insertion into the transcript. Subsequent screening of further unsolved CNGB3 subjects identified four additional cases harboring the c.1663-1205G>A variant which makes it the eighth most frequent CNGB3 variant in our cohort. Compound heterozygosity could be validated in ten cases. Our study demonstrates that whole gene sequencing can be a powerful approach to identify the second pathogenic allele in patients apparently harboring only one disease-causing variant.

Resolving the dark matter of ABCA4 for 1054 Stargardt disease probands through integrated genomics and transcriptomics.

PURPOSE: Missing heritability in human diseases represents a major challenge, and this is particularly true for ABCA4-associated Stargardt disease (STGD1). We aimed to elucidate the genomic and transcriptomic variation in 1054 unsolved STGD and STGD-like probands. METHODS: Sequencing of the complete 128-kb ABCA4 gene was performed using single-molecule molecular inversion probes (smMIPs), based on a semiautomated and cost-effective method. Structural variants (SVs) were identified using relative read coverage analyses and putative splice defects were studied using in vitro assays. RESULTS: In 448 biallelic probands 14 known and 13 novel deep-intronic variants were found, resulting in pseudoexon (PE) insertions or exon elongations in 105 alleles. Intriguingly, intron 13 variants c.1938-621G>A and c.1938-514G>A resulted in dual PE insertions consisting of the same upstream, but different downstream PEs. The intron 44 variant c.6148-84A>T resulted in two PE insertions and flanking exon deletions. Eleven distinct large deletions were found, two of which contained small inverted segments. Uniparental isodisomy of chromosome 1 was identified in one proband. CONCLUSION: Deep sequencing of ABCA4 and midigene-based splice assays allowed the identification of SVs and causal deep-intronic variants in 25% of biallelic STGD1 cases, which represents a model study that can be applied to other inherited diseases.

Transcorneal Electrical Stimulation for the Treatment of Retinitis Pigmentosa: A Multicenter Safety Study of the OkuStim® System (TESOLA-Study).

BACKGROUND: Transcorneal electrical stimulation (TES) has been suggested as a possible treatment for retinitis pigmentosa (RP). OBJECTIVE: To expand the safety assessment of repeated applications of an electrical current from a DTL-like electrode in patients with RP. METHODS: This single-arm open label interventional safety trial included a total of 105 RP patients from 11 European centers, who received weekly TES for 6 months on 1 eye followed by observation for another 6 months without stimulation. The primary outcome measure was safety, indicated by the frequency and severity of adverse events. Secondary measures included intraocular pressure and central retinal thickness. Visual field and visual acuity were examined using the methods available at each site. RESULTS: Dry eye sensation was the most common adverse event recorded (37.5%). Serious adverse events secondary to TES were not observed. Most adverse events were mild and all resolved without sequelae. The secondary outcome measures revealed no significant or clinically relevant changes. CONCLUSION: The present results confirm the excellent safety profile of TES. Transient dry eye symptoms were the most common adverse event.

Clinical Heterogeneity in Autosomal Recessive Bestrophinopathy with Biallelic Mutations in the BEST1 Gene.

Autosomal recessive bestrophinopathy (ARB) has been reported as clinically heterogeneous. Eighteen patients (mean age: 22.5 years; 15 unrelated families) underwent ophthalmological examination, fundus photography, fundus autofluorescence, and optical coherence tomography (OCT). Molecular genetic testing of the BEST1 gene was conducted by the chain-terminating dideoxynucleotide Sanger methodology. Onset of symptoms (3 to 50 years of age) and best-corrected visual acuity (0.02-1.0) were highly variable. Ophthalmoscopic and retinal imaging defined five phenotypes. Phenotype I presented with single or confluent yellow lesions at the posterior pole and midperiphery, serous retinal detachment, and intraretinal cystoid spaces. In phenotype II fleck-like lesions were smaller and extended to the far periphery. Phenotype III showed a widespread continuous lesion with sharp peripheral demarcation. Single (phenotype IV) or multifocal (phenotype V) vitelliform macular dystrophy-like lesions were observed as well. Phenotypes varied within families and in two eyes of one patient. In addition, OCT detected hyperreflective foci (13/36 eyes) and choroidal excavation (11/36). Biallelic mutations were identified in each patient, six of which have not been reported so far [c.454C>T/p.(Pro152Ser), c.620T>A/p.(Leu207His), c.287_298del/p.(Gln96_Asn99del), c.199_200del/p.(Leu67Valfs*164), c.524del/p.(Ser175Thrfs*19), c.590_615del/p.(Leu197Profs*26)]. BEST1-associated ARB presents with a variable age of onset and clinical findings, that can be categorized in 5 clinical phenotypes. Hyperreflective foci and choroidal excavation frequently develop as secondary manifestations.

Mutation-Dependent Pathomechanisms Determine the Phenotype in the Bestrophinopathies.

Best vitelliform macular dystrophy (BD), autosomal dominant vitreoretinochoroidopathy (ADVIRC), and the autosomal recessive bestrophinopathy (ARB), together known as the bestrophinopathies, are caused by mutations in the bestrophin-1 (BEST1) gene affecting anion transport through the plasma membrane of the retinal pigment epithelium (RPE). To date, while no treatment exists a better understanding of BEST1-related pathogenesis may help to define therapeutic targets. Here, we systematically characterize functional consequences of mutant BEST1 in thirteen RPE patient cell lines differentiated from human induced pluripotent stem cells (hiPSCs). Both BD and ARB hiPSC-RPEs display a strong reduction of BEST1-mediated anion transport function compared to control, while ADVIRC mutations trigger an increased anion permeability suggesting a stabilized open state condition of channel gating. Furthermore, BD and ARB hiPSC-RPEs differ by the degree of mutant protein turnover and by the site of subcellular protein quality control with adverse effects on lysosomal pH only in the BD-related cell lines. The latter finding is consistent with an altered processing of catalytic enzymes in the lysosomes. The present study provides a deeper insight into distinct molecular mechanisms of the three bestrophinopathies facilitating functional categorization of the more than 300 known BEST1 mutations that result into the distinct retinal phenotypes.

[Fundus Autofluorescence Imaging: Clinical Application and Diagnostic Relevance]. / Fundusautofluoreszenz: Klinische Anwendung und diagnostische Bedeutung.

Non-invasive fundus autofluorescence (FAF) imaging visualizes fluorophores at the level of the photoreceptors, the subneurosensory space and the retinal pigment epithelium. It gives important information over and above other imaging techniques. FAF imaging has improved the pathophysiological understanding of various retinal diseases. In combination with fundus photography, fluorescence angiography, optical coherence tomography, and electrophysiological examinations, FAF imaging is useful with regard to diagnostics and monitoring both during the natural course and after therapies. This review highlights basic principles of FAF and its clinical application in various retinal diseases.

[Congenital Retinal Dystrophies: Combining Ophthalmological Techniques to Improve the Read-out]. / Hereditäre Netzhautdystrophien: Kombination ophthalmologischer Methoden zur Optimierung des Readout.

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.