Management of macula-on giant retinal tear detachments- outcome of pars-plana-vitrectomy with silicone oil versus gas tamponade.

BACKGROUND: To compare the outcome of eyes with a macula-on giant retinal tear (GRT) detachment treated with pars-plana-vitrectomy (PPV) depending on the used endotamponade. METHODS: All consecutive cases with a macula-on GRT-associated rhegmatogenous retinal detachment (RRD) managed with PPV between 2007 and 2022 were retrospectively assessed depending on the selected endotamponade. By reviewing medical charts and surgical protocols the pre- and intraoperative parameters were analysed in detail. The number of vitreoretinal (VR) procedures needed for reattachment, the redetachment rate and the functional outcome were evaluated. Eyes treated with primary silicone oil (SO) tamponade were compared to eyes with primary gas tamponade. Cases with pre-existing conditions affecting outcome e.g. macula-off situation, history of trauma, status after complicated cataract surgery, former VR surgery or proliferative vitreoretinopathy grade C or higher were excluded. RESULTS: Overall, 51 eyes of 45 patients with a macula-on GRT detachment were treated with PPV and SO (n = 32; 63%) or gas (n = 19; 37%) endotamponade in the observed period. Eyes with primary SO tamponade underwent on average 2.3 (SD 0.8) VR procedures and had a redetachment rate of 13% (n = 4). Eyes with gas tamponade showed a higher redetachment rate of 32% (n = 6) with a mean number of 1.6 (SD 1.0) PPV procedures. Postoperative best-corrected visual acuity (BCVA) was significantly better in eyes with primary gas tamponade (mean logMAR BCVA 0.32; SD 0.30) compared to eyes with SO (mean logMAR BCVA 0.60; SD 0.42; p = 0.008). CONCLUSIONS: Surgical management of GRT-associated RRDs is complex. In clinical routine often SO is used as endotamponade. Because of known disadvantages (second procedure necessary for SO removal, unexplained SO-related visual loss, secondary glaucoma, SO emulsification) some VR surgeons prefer a gas tamponade. In our cohort, eyes with a gas compared to SO tamponade showed higher redetachment rates. However, the final postoperative BCVA was significantly better in eyes with gas compared to SO tamponade. TRIAL REGISTRATION: The trial protocol was approved by the local ethics committee on 25th of November 2022 (Ethikkommission der Universität Regensburg, Votum 22-3166-104).

Treated Cases of Retinopathy of Prematurity in Germany: 10-Year Data from the Retina.net Retinopathy of Prematurity Registry.

PURPOSE: To analyze changes in demographic parameters and retreatment patterns over a 10-year period in a clinical routine setting of infants with retinopathy of prematurity (ROP) requiring treatment documented in the German Retina.net ROP registry. DESIGN: Multicenter, noninterventional, observational registry study recruiting patients treated for ROP. SUBJECTS: A total of 692 eyes of 353 infants treated for ROP were documented in the Retina.net ROP registry over a 10-year period between 2011 and 2020. These cases cover about 15% of all infants treated for ROP in Germany. METHODS: The Retina.net ROP registry was established in 2012 to jointly collect information on infants treated for ROP. The database collects information on demographic parameters (gestational age [GA], birth weight, neonatal comorbidities) as well as treatment parameters (type of treatment, weight and age at treatment, and stage of ROP). A total of 19 centers contributed to the analysis. This is the 10-year analysis of data from 2011 to 2020, in which we focus on changes over time regarding the respective parameters. MAIN OUTCOME MEASURES: Changes over time in demographic parameters and treatment patterns for ROP in Germany. RESULTS: The overall incidence of treatment requiring ROP was 3.5% of all infants screened for ROP at participating centers. Gestational age, weight at birth, and weight at treatment remained stable over the 10-year period, whereas postmenstrual and postnatal age at treatment increased moderately but statistically significantly over the years. The most prevalent ROP severity stage at treatment was stage 3+ in zone II (76.6% of all treated eyes). Treatment patterns changed considerably from predominantly laser treatments in 2011 (75% of all treated eyes) to predominantly ranibizumab treatments in 2020 (60.9% of all treated eyes). The overall retreatment rate was 15.6%. Retreatment rates differed between initial treatment modalities (14.1% after laser coagulation, 12% after bevacizumab and 24.5% after ranibizumab). Treatment-associated systemic or ophthalmic complications were rare. CONCLUSIONS: This data analysis represents one of the largest documented cohorts of infants treated for ROP. The data on demographic parameters and treatment patterns provide useful information for further improvement of ROP management. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Long-Term Outcome and Complications of IOL-Exchange.

Purpose: To describe the long-term outcome after intraocular lens (IOL) exchange for IOL-opacification with a focus on any occurring complications. Patients and Methods: Patients with an IOL exchange for opacified IOLs (Lentis LS-502-1) were identified. Medical records and information from the treating ophthalmologists were reviewed. Visual outcomes and any occurring complications after the IOL exchange were analyzed. Results: IOL exchange was performed in 48 eyes of 46 patients and significantly improved best-corrected distance visual acuity from 0.42 ± 0.32 logMar (mean ± SD) in opacified lenses to 0.25 ± 0.28 logMar after IOL exchange. Nine of the 48 eyes (19%) underwent 11 further surgical procedures for complications due to four indications: IOL dislocation (n = 2, 4%), retinal detachment (RD) (n = 6, 12%), epiretinal membrane (n = 2, 4%), and pupillary block (n = 1, 2%). Three eyes (6%) developed a temporarily elevated intraocular pressure. Temporary postoperative cystoid macular edema was found in 2 eyes (4%). Conclusion: IOL exchange can restore vision owing to IOL opacification in most cases. Nonetheless, IOL exchange is not an easy or risk-free procedure. This may lead to sight-threatening complications, even in eyes without predisposing ocular comorbidities.

A unified classification approach rating clinical utility of protein biomarkers across neurologic diseases.

A major evolution from purely clinical diagnoses to biomarker supported clinical diagnosing has been occurring over the past years in neurology. High-throughput methods, such as next-generation sequencing and mass spectrometry-based proteomics along with improved neuroimaging methods, are accelerating this development. This calls for a consensus framework that is broadly applicable and provides a spot-on overview of the clinical validity of novel biomarkers. We propose a harmonized terminology and a uniform concept that stratifies biomarkers according to clinical context of use and evidence levels, adapted from existing frameworks in oncology with a strong focus on (epi)genetic markers and treatment context. We demonstrate that this framework allows for a consistent assessment of clinical validity across disease entities and that sufficient evidence for many clinical applications of protein biomarkers is lacking. Our framework may help to identify promising biomarker candidates and classify their applications by clinical context, aiming for routine clinical use of (protein) biomarkers in neurology.

Current Practice in the Treatment of Epithelial and Melanocytic Tumours with Interferon-α2b: A Survey of Tertiary Eye Centres in Germany.

PURPOSE: To evaluate the standard of care, in particular the use of topical or subconjunctival interferon-α2b, in treating ocular surface squamous neoplasia or melanocytic tumours in tertiary eye centres in Germany. METHODS: A survey containing 14 questions was sent to 43 tertiary eye centres in Germany. The questions addressed the surgical and medical management of ocular surface squamous neoplasia and melanocytic tumours (primary acquired melanosis and malignant melanoma), as well as the clinical experiences and difficulties in prescribing off-label interferon-α2b eye drops and subconjunctival injections. RESULTS: Twenty-four tertiary eye centres responded to the survey. Eighty-three percent of centres had used interferon-α2b in their clinical practice and 25% prescribed it as the first-line cytostatic agent following surgical excision of ocular surface squamous neoplasia, while 10% would do so for melanocytic tumours. Correspondingly, the majority of respondents selected mitomycin C as their first-line agent. Side effects were uncommon with topical interferon-α2b eye drops but were more frequently reported after subconjunctival interferon-α2b injections. In total, eight centres had experience with interferon-α2b injections. The most significant obstacles perceived by ophthalmologists when prescribing interferon-α2b were its high cost and the reimbursement thereof. CONCLUSION: Off-label mitomycin C was the preferred adjuvant therapy for epithelial and melanocytic tumours, with interferon-α2b being the standard second-line option. Interferon-α2b has predominantly been used to treat ocular surface squamous neoplasia and, to a lesser extent, melanocytic tumours at German tertiary eye centres. Following its market withdrawal, supply shortages of interferon-α2b are likely to have a profound impact on patient care and their quality of life.

Assessment of Retinopathy of Prematurity Regression and Reactivation Using an Artificial Intelligence-Based Vascular Severity Score.

Importance: One of the biggest challenges when using anti-vascular endothelial growth factor (VEGF) agents to treat retinopathy of prematurity (ROP) is the need to perform long-term follow-up examinations to identify eyes at risk of ROP reactivation requiring retreatment. Objective: To evaluate whether an artificial intelligence (AI)-based vascular severity score (VSS) can be used to analyze ROP regression and reactivation after anti-VEGF treatment and potentially identify eyes at risk of ROP reactivation requiring retreatment. Design, Setting, and Participants: This prognostic study was a secondary analysis of posterior pole fundus images collected during the multicenter, double-blind, investigator-initiated Comparing Alternative Ranibizumab Dosages for Safety and Efficacy in Retinopathy of Prematurity (CARE-ROP) randomized clinical trial, which compared 2 different doses of ranibizumab (0.12 mg vs 0.20 mg) for the treatment of ROP. The CARE-ROP trial screened and enrolled infants between September 5, 2014, and July 14, 2016. A total of 1046 wide-angle fundus images obtained from 19 infants at predefined study time points were analyzed. The analyses of VSS were performed between January 20, 2021, and November 18, 2022. Interventions: An AI-based algorithm assigned a VSS between 1 (normal) and 9 (most severe) to fundus images. Main Outcomes and Measures: Analysis of VSS in infants with ROP over time and VSS comparisons between the 2 treatment groups (0.12 mg vs 0.20 mg of ranibizumab) and between infants who did and did not receive retreatment for ROP reactivation. Results: Among 19 infants with ROP in the CARE-ROP randomized clinical trial, the median (range) postmenstrual age at first treatment was 36.4 (34.7-39.7) weeks; 10 infants (52.6%) were male, and 18 (94.7%) were White. The mean (SD) VSS was 6.7 (1.9) at baseline and significantly decreased to 2.7 (1.9) at week 1 (P < .001) and 2.9 (1.3) at week 4 (P < .001). The mean (SD) VSS of infants with ROP reactivation requiring retreatment was 6.5 (1.9) at the time of retreatment, which was significantly higher than the VSS at week 4 (P < .001). No significant difference was found in VSS between the 2 treatment groups, but the change in VSS between baseline and week 1 was higher for infants who later required retreatment (mean [SD], 7.8 [1.3] at baseline vs 1.7 [0.7] at week 1) vs infants who did not (mean [SD], 6.4 [1.9] at baseline vs 3.0 [2.0] at week 1). In eyes requiring retreatment, higher baseline VSS was correlated with earlier time of retreatment (Pearson r = -0.9997; P < .001). Conclusions and Relevance: In this study, VSS decreased after ranibizumab treatment, consistent with clinical disease regression. In cases of ROP reactivation requiring retreatment, VSS increased again to values comparable with baseline values. In addition, a greater change in VSS during the first week after initial treatment was found to be associated with a higher risk of later ROP reactivation, and high baseline VSS was correlated with earlier retreatment. These findings may have implications for monitoring ROP regression and reactivation after anti-VEGF treatment.

Characteristics of Bilateral Retinal Detachment.

INTRODUCTION: Rhegmatogenous retinal detachment (RD) is still a sight-threatening and potentially blinding disease, especially if both eyes are affected. The purpose of this study is analysing the specific characteristics of bilateral rhegmatogenous RD. METHODS: The files of all 5,791 consecutive eyes undergoing vitreoretinal surgery for uncomplicated RD in a single tertiary retinal centre between January 2005 and June 2021 were retrospectively reviewed. RESULTS: A total of 300 patients (600 eyes) had bilateral retinal detachment. Interval between initial and subsequent RD surgery was 2.6 ± 2.8 (mean ± SD, median 1.5) years. Symptoms were reported by the patients for 20 ± 75 (median 5) days before presentation in the initial eye and 12 ± 32 (median 4) days in the subsequent eye. 220 patients were male (73%), and mean age at initial RD was 55 years. 183 (61%) of the initial RD eyes were phakic. In the initial eye, more patients had a detached macula, worse visual acuity, and more quadrants involved. Primary anatomic success rate was higher in the subsequent eye (90%) compared to the initial eye (83%). There was no difference in the reattachment rate of fellow eyes with primary failure in the first eye (91%) compared to those with primary success in the first eye (90%). There was a high symmetry between the eyes in terms of type of retinal break, number of breaks, and presumed localization of the causative retinal break. CONCLUSION: Patients with bilateral RD were more commonly male and younger than the group of all RD patients. The proportion of pseudophakia was not different. The majority of fellow eye RD occurred within 2 years after the RD in the first eye. Second eye RD was less advanced and had a better anatomical repair rate. Despite their experience in the first eye and despite typical symptoms, patients presented only after a mean of 12 days with RD in the second eye. RD in the initial and the subsequent eye showed a high symmetry. The anatomic result in the first eye is not a predictor for the anatomic result in the subsequent eye.

Rhegmatogenous retinal detachment repair-does age, sex, and lens status make a difference?

PURPOSE: To analyze the correlation between lens status, age, and sex in the epidemiology and success rates of rhegmatogenous retinal detachment (RRD) surgery. METHODS: The files of all consecutive patients undergoing vitreoretinal surgery for uncomplicated RRD between Jan 2005 und Dec 2020 were retrospectively reviewed. Successful outcome was defined as no retinal redetachment occurring within 3 months after surgery. RESULTS: 5502 eyes with uncomplicated primary RRD were included. Mean age of the patients was 61.1 years (± 13.6 SD). In the age group over 40 years, a male predominance was found. The percentage of pseudophakic RRD increased from 25 to 40% during the 15 years observation period. In the age group 50 to 69 years, patients with pseudophakic detachments were male in 786 out of 1079 cases (72.9%). In the same age group, 1285 of 2110 (60.9%) patients with phakic RRD were male. Overall, primary success rate after one procedure was 91.2% (5018 of 5502). In the phakic eyes, the primary success rate was higher in those eyes that underwent combined phacovitrectomy (93.0%), compared to those without simultaneous cataract surgery (88.7%; p = 0.002). CONCLUSION: The ratio of male and female patients with RRD varies between age groups. The proportion of pseudophakic RRD has increased within 15 years. The male predominance in RRD is stronger in pseudophakic than in phakic eyes. In phakic eyes with RRD, a combined phacovitrectomy yielded better anatomical results.

Incidence, progression and risk factors of age-related macular degeneration in 35-95-year-old individuals from three jointly designed German cohort studies.

OBJECTIVE: To estimate age-related macular degeneration (AMD) incidence/progression across a wide age range. METHODS AND ANALYSIS: AMD at baseline and follow-up (colour fundus imaging, Three Continent AMD Consortium Severity Scale, 3CACSS, clinical classification, CC) was assessed for 1513 individuals aged 35-95 years at baseline from three jointly designed population-based cohorts in Germany: Kooperative Gesundheitsforschung in der Region Augsburg (KORA-Fit, KORA-FF4) and Altersbezogene Untersuchungen zur Gesundheit der Universität Regensburg (AugUR) with 18-year, 14-year or 3-year follow-up, respectively. Baseline assessment included lifestyle, metabolic and genetic markers. We derived cumulative estimates, rates and risk factor association for: (1) incident early AMD, (2) incident late AMD among no AMD at baseline (definition 1), (3) incident late AMD among no/early AMD at baseline (definition 2), (4) progression from early to late AMD. RESULTS: Incidence/progression increased by age, except progression in 70+-year old. We observed 35-55-year-old with 3CACSS-based early AMD who progressed to late AMD. Predominant risk factor for incident late AMD definition 2 was early AMD followed by genetics and smoking. When separating incident late AMD definition 1 from progression (instead of combined as incident late AMD definition 2), estimates help judge an individual's risk based on age and (3CACSS) early AMD status: for example, for a 65-year old, 3-year late AMD risk with no or early AMD is 0.5% or 7%, 3-year early AMD risk is 3%; for an 85-year old, these numbers are 0.5%, 21%, 12%, respectively. For CC-based 'early/intermediate' AMD, incidence was higher, but progression was lower. CONCLUSION: We provide a practical guide for AMD risk for ophthalmology practice and healthcare management and document a late AMD risk for individuals aged <55 years.

[Retinal detachment surgery: trends over 15 years]. / Ablatiochirurgie: Trends über 15 Jahre.

INTRODUCTION: The aim of the study was to investigate the changes in the treatment of patients with retinal detachment over the past 15 years. METHOD: Files of all 5101 patients hospitalized for retinal detachment surgery between January 2005 and March 2020 were retrospectively analyzed. RESULTS: The number of retinal detachment surgeries over the past 15 years increased continually from 150 to 600 per annum. During the summer months an increased incidence of retinal detachment of approximately 20% could be observed compared to the winter months. Anatomical success rates of emergency surgery carried out at weekends were not lower than those of scheduled routine procedures performed during the week. The relative proportion of buckle surgery decreased significantly from more than 60% down to 5% between 2005 and 2019. While initially an additional encircling buckle was employed in most cases of primary vitrectomy, this technique has almost completely disappeared in recent years without a deterioration of success rates. Liquid silicone tamponade was applied less frequently over the years. The overall anatomical success rates showed a slight trend towards improved results over the past 15 years. CONCLUSION: The strategies for surgical repair of retinal detachment have changed considerably in recent years: less buckle surgery, more vitrectomy, less add-on encircling buckles and less silicone tamponade. A slight trend towards better anatomical success rates could be observed.

Ranibizumab in retinopathy of prematurity - one-year follow-up of ophthalmic outcomes and two-year follow-up of neurodevelopmental outcomes from the CARE-ROP study.

PURPOSE: The primary endpoint results from the comparing alternative ranibizumab dosages for safety and efficacy in retinopathy of prematurity (CARE-ROP) core study identified ranibizumab as an effective treatment to control acute retinopathy of prematurity (ROP). This study reports the 1- and 2-year follow-up data focusing on long-term functional outcomes and safety. METHODS: The CARE-ROP trial compared 0.12 mg versus 0.20 mg ranibizumab in 20 infants with ROP in a multicentric, prospective, randomized, double-blind, controlled study design. Sixteen patients entered the follow-up period. An ophthalmologic assessment at one year postbaseline was acquired from all 16 patients and a neurodevelopmental assessment at two years postbaseline was acquired from 15 patients. RESULTS: Fifteen of 16 infants were able to fixate and follow moving objects at one year postbaseline treatment. One child progressed to stage 5 ROP bilaterally between the end of the core study and the 1-year follow-up (first seen at PMA 75 weeks). Mean spherical equivalents were -1.9 diopters (D) and -0.75 D in the 0.12 mg and the 0.20 mg treatment arms. Strabismus was present in seven and nystagmus in five out of 16 infants. Mental development scores were within normal limits in six out of ten patients with available data. No statistically significant difference was observed between the two treatment arms. CONCLUSION: Neurodevelopmental and functional ocular outcomes 1 and 2 years after treatment with ranibizumab are reassuring regarding long-term safety. Late reactivation of ROP, however, represents a challenge during the follow-up phase and it is of utmost importance that regular follow-ups are maintained.

[Diabetic retinopathy]. / Diabetische Retinopathie.

Diabetic retinopathy (DR) is a vision-threatening microvascular complication of diabetes and the leading cause of blindness in working-age people. At the beginning of the metabolic disorder and in early stages of DR the patient's eyesight is often not affected. Depending on the duration of diabetes and in more advanced stages of DR the vision is compromised through the presence of diabetic macular edema (DME) and/or proliferative retinal complications. The management of DR comprises regular ophthalmic examinations according to clinical guidelines, the targeted application of multimodal imaging, and the specific treatment of DME and proliferative DR including secondary disorders such as neovascular glaucoma or persistent vitreous haemorrhage. Innovative ocular imaging techniques like optical coherence tomography (OCT), OCT angiography (OCT-A) and ultrawide field imaging play an important role in the assessment of diabetic patients. Various non-invasive imaging modalities have become part of the routine clinical work-up and help to identify new biomarkers for early diagnosis and long-term prognosis. In early stages of DR, the multifactorial intervention including glucose level and blood pressure control as well as optimizing the patient's cardiovascular risk profile is essential. A specific ophthalmic therapy is available for DME and proliferative DR (PDR). In patients with PDR the treatment regime includes panretinal laser photocoagulation or alternatively intravitreal anti-VEGF (vascular endothelial growth factor)-injections accompanied by close-meshed clinical monitoring. In patients with both, DME and PDR, it is suggested to start with Anti-VEGF drugs. In severe PDR with persistent vitreous haemorrhage, tractional maculopathy or tractional retinal detachment vitreoretinal surgery is recommended.

[Diabetic Macular Edema]. / Diabetisches Makulaödem.

Diabetic macular edema (DME) is a chronic retinal disease, which requires intensive clinical monitoring. Within the last ten years the intravitreal anti-VEGF (vascular endothelial growth factor) therapy has become the standard of care to improve and stabilize vision in patients with centre involving DME. Long-acting intravitreal corticosteroids can achieve similar visual results with fewer injection rates. Because of steroid-induced side effects (progression of cataract, glaucoma) these drugs are regarded as second-line medication. Since the introduction of anti-VEGF-medication the focal laser photocoagulation is no longer considered as first-line therapy for DME. However, a focal laser treatment can sometimes be a possible alternative in specific situations. In patients with proliferative diabetic retinopathy and DME, the intravitreal anti-VEGF therapy is approved for both conditions. In ischemic maculopathy the functional outcome is restricted. For the indication of anti-VEGF-treatment for DME with accompanying central ischemia not only visual acuity and optical coherence tomography parameters should be considered, the amount of ischemia seen on fluorescein angiography should also be taken into account. In tractional macular edema due to epiretinal membranes and vitreomacular adhesions a pars-plana vitrectomy with membrane peeling is indicated.

The learning curve of retinal detachment surgery.

PURPOSE: To investigate the learning curve of vitreoretinal (VR) surgeons beginning training in retinal detachment (RD) surgery. METHODS: The files of all consecutive patients undergoing VR surgery for uncomplicated RD between Jan 2005 und Mar 2020 were retrospectively reviewed. Successful outcome was defined as no retinal redetachment within 3 months after surgery. RESULTS: Ten surgeons started their VR career during this period. Together, these 10 surgeons performed 3786 RD operations (mean 379; median 251; range 71-1053). Primary success rate after one operation was 90% (3420 of 3786). When starting to operate retinal detachments, VR surgeons had a primary success rate of about 80%. Redetachment rates steadily decreased and stabilized at just under 10% after about 200 operations. Beginners needed more than twice the time for the procedure compared to experienced surgeons. The individual learning curves varied widely. In our series, female surgeons seem to have a faster learning curve. CONCLUSION: RD surgery performed by VR surgeons in training had acceptable results. With increasing experience, success rates continuously improve reaching stable levels after approximately 200 operations. The training of VR surgeons requires considerable resources.

SETDB1-dependent heterochromatin stimulates alternative lengthening of telomeres.

Alternative lengthening of telomeres, or ALT, is a recombination-based process that maintains telomeres to render some cancer cells immortal. The prevailing view is that ALT is inhibited by heterochromatin because heterochromatin prevents recombination. To test this model, we used telomere-specific quantitative proteomics on cells with heterochromatin deficiencies. In contrast to expectations, we found that ALT does not result from a lack of heterochromatin; rather, ALT is a consequence of heterochromatin formation at telomeres, which is seeded by the histone methyltransferase SETDB1. Heterochromatin stimulates transcriptional elongation at telomeres together with the recruitment of recombination factors, while disrupting heterochromatin had the opposite effect. Consistently, loss of SETDB1, disrupts telomeric heterochromatin and abrogates ALT. Thus, inhibiting telomeric heterochromatin formation in ALT cells might offer a new therapeutic approach to cancer treatment.

Detection of Histone Modification Dynamics during the Cell Cycle by MS-Based Proteomics.

DNA replication and subsequent deposition of nucleosomes is critical for the maintenance of the genome and epigenetic inheritance. Experiments using human tissue culture cells harvested at defined stages of the cell cycle can help to elucidate the mechanism of histone deposition and chromatin assembly in detail. Here, we describe a pulsed-SILAC approach to distinguish newly synthesized and deposited histones during S-phase of the cell cycle from parental "old" histones incorporated in previous replications and to decipher posttranslational histone modifications (PTMs).

Intravitreal anti-VEGF treatment for subretinal neovascularisation secondary to type 2 idiopathic juxtafoveolar telangiectasia.

PURPOSE: To assess the long-term outcome of patients with subretinal neovascular membrane (SRNVM) secondary to type 2 idiopathic juxtafoveolar telangiectasia (IJT) receiving intravitreal anti-VEGF (vascular endothelial growth factor) injections. METHODS: A total of 14 eyes of 12 patients treated with intravitreal anti-VEGF for SRNVM related to type 2 IJT were retrospectively assessed. RESULTS: Nine men and 3 women with a mean age of 66 years (SD 12, range 47-87 years) were diagnosed with IJT-related SRNVM. On average, 6.8 injections (SD 5.5, range 3-18) were given per eye. Ten eyes were treated with ranibizumab, 3 eyes with bevacizumab and 1 eye received both substances. The median follow-up after the last injection was 31 months (IQR: 18, 48). In 6 eyes, BCVA improved by 1-4 lines (mean Δ +2.0 lines), 1 eye remained stable and 7 eyes showed decline of vision by 1-5 lines (mean Δ -2.1 lines). The baseline central foveal thickness was significantly reduced from a mean of 323 (SD 87) to 266 µm (SD 71 µm) at the last follow-up visit (p = 0.001). CONCLUSIONS: SRNVM development is a severe complication of type 2 IJT. Since the establishment of intravitreal anti-VEGF treatment laser coagulation and PDT have lost significance. Intravitreal anti-VEGF therapy seems to be safe and effective for the treatment of IJT-related SRNVM. Frequently multiple intravitreal injections are necessary for stabilisation.

Clinical Features and Outcome of Paediatric Retinal Detachment.

PURPOSE: The aim of this study was to assess the clinical features and outcome of paediatric retinal detachment (RD). METHODS: Ninety-five eyes of 87 children under 18 years of age with RD were assessed. The risk factors, morphology of RD, therapeutic approach and functional results were evaluated. RESULTS: Sixty-seven boys and 20 girls with a mean age of 10.4 years (standard deviation 5.5) presented with RD. The following risk factors were identified: myopia (23%), congenital or developmental ocular abnormalities (37%), history of ocular trauma (40%) and previous ocular surgery (27%). Seventy-seven (81%) eyes underwent surgery. The primary reattachment rate was 44%. In 18%, reattachment was achieved after several surgeries. The overall recurrence rate after surgical reattachment was 39%. CONCLUSIONS: Paediatric RD is a sight-threatening condition. Often, aggravating factors, such as delayed diagnosis, hereditary ocular abnormalities or strong vitreous adherence, are present. Hopefully, modern surgical techniques may contribute to a better outcome of RD in the future.

Etiology and treatment of choroidal neovascularization in pediatric patients.

PURPOSE: To assess the etiology, clinical features, and outcome of choroidal neovascularization (CNV) in children. METHODS: We retrospectively assessed 10 eyes of 8 patients younger than 18 years diagnosed with CNV. The main clinical parameters included predisposing ocular pathologies, best-corrected visual acuity before and after treatment, characteristics of CNV, and treatment modalities. RESULTS: Two boys and 6 girls with CNV and a mean age of 13.9 years (SD 1.9, range 11-16 years) were included. Two patients developed bilateral CNV within the follow-up time. The development of CNV was secondary to the following pathologies: choroidal osteoma (n = 3), pathologic myopia (n = 1), punctate inner choroidopathy (n = 1), hereditary macular dystrophy (n = 2), and angioid streaks (n = 1). Idiopathic CNV was diagnosed in 2 children without any obvious associated ocular pathology. In 9 eyes, CNV was treated by intravitreal anti-vascular endothelial growth factor (VEGF) administration (n = 6), photodynamic therapy (n = 1), or combination therapy (n = 3). One eye remained untreated because of advanced disease. CONCLUSIONS: Pediatric CNV is a rare but sight-threatening retinal disease. So far, no standard treatment has been validated. Since the establishment of intravitreal anti-VEGF therapy, laser coagulation and photodynamic therapy have lost their significance as therapy for CNV.

Redundant mechanisms to form silent chromatin at pericentromeric regions rely on BEND3 and DNA methylation.

Constitutive heterochromatin is typically defined by high levels of DNA methylation and H3 lysine 9 trimethylation (H3K9Me3), whereas facultative heterochromatin displays DNA hypomethylation and high H3 lysine 27 trimethylation (H3K27Me3). The two chromatin types generally do not coexist at the same loci, suggesting mutual exclusivity. During development or in cancer, pericentromeric regions can adopt either epigenetic state, but the switching mechanism is unknown. We used a quantitative locus purification method to characterize changes in pericentromeric chromatin-associated proteins in mouse embryonic stem cells deficient for either the methyltransferases required for DNA methylation or H3K9Me3. DNA methylation controls heterochromatin architecture and inhibits Polycomb recruitment. BEND3, a protein enriched on pericentromeric chromatin in the absence of DNA methylation or H3K9Me3, allows Polycomb recruitment and H3K27Me3, resulting in a redundant pathway to generate repressive chromatin. This suggests that BEND3 is a key factor in mediating a switch from constitutive to facultative heterochromatin.