Publications by authors named "Carsten Framme"

83 Publications

Selective retina therapy and thermal stimulation of the retina: different regenerative properties - implications for AMD therapy.

BMC Ophthalmol 2021 Nov 30;21(1):412. Epub 2021 Nov 30.

Department of Ophthalmology, Christian-Albrechts-University of Kiel, University Medical Center, Kiel, Germany.

Background: Selective Retina Therapy (SRT), a photodisruptive micropulsed laser modality that selectively destroys RPE cells followed by regeneration, and Thermal Stimulation of the Retina (TSR), a stimulative photothermal continuous wave laser modality that leads to an instant sublethal temperature increase in RPE cells, have shown therapeutic effects on Age-related Macular Degeneration (AMD) in mice. We investigate the differences between both laser modalities concerning RPE regeneration.

Methods: For PCR array, 6 eyes of murine AMD models, apolipoprotein E and nuclear factor erythroid-derived 2- like 2 knock out mice respectively, were treated by neuroretina-sparing TSR or SRT. Untreated litter mates were controls. Eyes were enucleated either 1 or 7 days after laser treatment. For morphological analysis, porcine RPE/choroid organ cultures underwent the same laser treatment and were examined by calcein vitality staining 1 h and 1, 3 or 5 days after irradiation.

Results: TSR did not induce the expression of cell-mediators connected to cell death. SRT induced necrosis associated cytokines as well as inflammation 1 but not 7 days after treatment. Morphologically, 1 h after TSR, there was no cell damage. One and 3 days after TSR, dense chromatin and cell destruction of single cells was seen. Five days after TSR, there were signs of migration and proliferation. In contrast, 1 h after SRT a defined necrotic area within the laser spot was seen. This lesion was closed over days by migration and proliferation of adjacent cells.

Conclusions: SRT induces RPE cell death, followed by regeneration within a few days. It is accompanied by necrosis induced inflammation, RPE proliferation and migration. TSR does not induce immediate RPE cell death; however, migration and mitosis can be seen a few days after laser irradiation, not accompanied by necrosis-associated inflammation. Both might be a therapeutic option for the treatment of AMD.
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http://dx.doi.org/10.1186/s12886-021-02188-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8630886PMC
November 2021

[Epidemiology and treatment of retinopathy of prematurity. The Hannover data in the Retina.net ROP registry from 2001-2017].

Ophthalmologe 2021 Nov 22. Epub 2021 Nov 22.

Universitätsklinik für Augenheilkunde, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625, Hannover, Deutschland.

Background: The Retina.net ROP registry documents data of preterm infants developing stages of retinopathy of prematurity (ROP) that need ROP treatment. The aim of this analysis was to investigate data regarding epidemiology, therapy and changes over time (15 years) in a single participating center (Hannover Medical School, MHH).

Methods: Analysis of data of infants treated for ROP at a single center over time (birth 2001-2016, ROP treatment in 2002-2017).

Results: Overall, 65 infants were treated (23 female). In 11 infants (16.9%) ROP screening was conducted externally and infants were transferred to the MHH for ROP treatment. Between 2006 and 2016, incidence of ROP requiring treatment among infants screened for the development of ROP was 4.1%. Mean gestational age was 25.7 weeks (standard deviation, SD 1.8), mean birth weight 763 g (SD 235), postmenstrual age at treatment 38.2 weeks (SD 3.2), postnatal age 12.4 weeks (SD 3.2). There was no significant change in parameters over time. ROP zone II, stage 3+ was most frequently treated (57 eyes of 31 infants). 58 infants were treated with laser (114 eyes), 7 infants were treated with anti-VEGF (bevacizumab, bilateral, 14 eyes) from 2014 onwards. Retreatment due to recurrence of ROP was necessary in one infant after initial laser coagulation. Infants with ROP requiring treatment often presented with neonatal comorbidities, ventilation in more than 90%, bronchopulmonary dysplasia, and received transfusions.

Conclusion: This is the first monocentric analysis over 15 years originating from the Retina.net ROP registry. In this cohort we see a change in ROP therapy from laser coagulation to anti-VEGF (bevacizumab) from 2014 onwards, demographic data and treatment parameters remained relatively stable over time.
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http://dx.doi.org/10.1007/s00347-021-01528-9DOI Listing
November 2021

Measurement of tear resistance after manual capsulorhexis and femtosecond laser-assisted capsulotomy of crystalline lenses.

Lasers Med Sci 2021 Oct 29. Epub 2021 Oct 29.

Industrial and Biomedical Optics Department, Laser Zentrum Hannover E.V, Hannover, Germany.

Background: In this study, the tear resistance of porcine lens capsules after continuous curvilinear capsulorhexis (CCC) and femtosecond (fs)-laser-assisted capsulotomy for cataract surgery (FLC) with different laser parameters is measured with a custom-made testing setup.

Methods: Forty-five fresh porcine lenses were randomly chosen for CCC (n = 15) or FLC 1 (n = 15) and FLC 2 (n = 15). The FLC 1-group was treated with smaller spot distances than the FLC 2-group. The force necessary to break the opening of the anterior capsule and the maximum displacement were measured.

Results: The mean tear resistance of the CCC-group (150 ± 70 mN) was higher than that of the FLC 1-group (60 ± 20 mN) and the FLC 2-group (30 ± 20 mN).

Conclusion: It could be shown that CCC leads to a significantly higher tear resistance of the opening than FLC in porcine lenses. The femtosecond laser group demonstrated that smaller spot distances lead to a higher tear resistance.
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http://dx.doi.org/10.1007/s10103-021-03448-1DOI Listing
October 2021

PERSEUS 24-month analysis: a prospective non-interventional study to assess the effectiveness of intravitreal aflibercept in routine clinical practice in Germany in patients with neovascular age-related macular degeneration.

Graefes Arch Clin Exp Ophthalmol 2021 Aug 6;259(8):2213-2223. Epub 2021 Feb 6.

Klinik für Augenheilkunde, Medizinische Hochschule Hannover, Hannover, Germany.

Purpose: To evaluate the real-world effectiveness of intravitreal aflibercept injections in Germany in patients with neovascular age-related macular degeneration over 24 months.

Methods: PERSEUS was a prospective, non-interventional cohort study. The primary endpoint was the mean change in visual acuity (VA) from baseline. Secondary endpoints included the proportion of patients with a VA gain or loss of ≥ 15 letters and the frequency of injections and examinations. Patients with regular (bimonthly after 3 monthly injections during year 1 and ≥ 4 injections in year 2) and irregular (any other) treatment were analyzed. The last observation carried forward (LOCF) and the observed cases (OC) approach was applied for primary endpoint analysis to account for missing data.

Results: 803 patients were considered for effectivity analysis. At month 24, only 38% of the patients were still under observation. The LOCF population included 727, the OC population 279 patients. Treatment-naïve patients improved by 6.3 (LOCF)/8.1 (OC) letters with regular treatment over 24 months but only by 3.3 (LOCF)/3.1 (OC) letters with irregular treatment. The proportion of treatment-naïve patients achieving a VA improvement of ≥ 15 letters was similar between regularly and irregularly treated cohorts. However, considerably more patients in the irregular cohorts experienced a VA worsening of ≥ 15 letters than in the regular cohorts (LOCF: 18.7% vs. 7.4%).

Conclusions: Regular IVT-AFL treatment resulted in better VA outcomes than irregular treatment at month 24. However, only a minority of patients received regular treatment over a 2-year period.
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http://dx.doi.org/10.1007/s00417-021-05073-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8352822PMC
August 2021

Human Amniotic Membrane: A review on tissue engineering, application, and storage.

J Biomed Mater Res B Appl Biomater 2021 08 14;109(8):1198-1215. Epub 2020 Dec 14.

Institute for Multiphase Processes, Leibniz University Hannover, Garbsen, Germany.

Human amniotic membrane (hAM) has been employed as scaffolding material in a wide range of tissue engineering applications, especially as a skin dressing and as a graft for corneal treatment, due to the structure of the extracellular matrix and excellent biological properties that enhance both wound healing and tissue regeneration. This review highlights recent work and current knowledge on the application of native hAM, and/or production of hAM-based tissue-engineered products to create scaffolds mimicking the structure of the native membrane to enhance the hAM performance. Moreover, an overview is presented on the available (cryo) preservation techniques for storage of native hAM and tissue-engineered products that are necessary to maintain biological functions such as angiogenesis, anti-inflammation, antifibrotic and antibacterial activity.
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http://dx.doi.org/10.1002/jbm.b.34782DOI Listing
August 2021

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

Int J Mol Sci 2020 Dec 8;21(24). Epub 2020 Dec 8.

Zentrum für Seltene Netzhauterkrankungen, AugenZentrum Siegburg, MVZ Augenärztliches Diagnostik- und Therapiecentrum Siegburg GmbH, Europaplatz 3, 53721 Siegburg, Germany.

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 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)]. -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.
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http://dx.doi.org/10.3390/ijms21249353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763028PMC
December 2020

Development of a Patient-Oriented Organizational Management System for Intravitreal Injection Therapy in a Standardized "Treat-and-Extend" Regime at a University Eye Clinic.

Klin Monbl Augenheilkd 2020 Nov 26. Epub 2020 Nov 26.

Universitätsklinik für Augenheilkunde, Medizinische Hochschule Hannover, Deutschland.

Background: The treatment of macular edema with intravitreal injections has revolutionized the treatment of associated diseases in ophthalmology. However, with a few exceptions, this is a chronic treatment where patients require many injections and usually need to stay in treatment for years. Patient adherence and control of patient flow are critical to treatment success. In this manuscript, we describe the development of a patient-oriented organization management for intravitreal injections in a university hospital.

Material And Methods: In 2015, the intravitreal treatment in our clinic was switched to the treat-and-extend regime. At the same time, the optimization of the previous organizational processes in perioperative management was evaluated. For the period 2015 to 2018, we analyzed and gradually optimized the procedures of our intravitreal injection therapy in a survey with a specialized service provider.

Results: Through the analysis of the original processes, the patient appointment was optimized, work processes were summarized, spatially reorganized and there was only a slight increase in the number of staff involved compared with the significant increase in the number of injections. Through these measures, the total in-hospital-time of the patients could be drastically reduced and at the same time the number of patients on one operation day could be multiplied.

Conclusion: In the context of chronic treatment with intravitreal injections, the care of an increased number of patients is a logistical challenge. By optimizing processes, existing resources can be better used to meet the increased demands. An optimized system offers the patient greater adherence and a better visual outcome largely independent of the medication used.
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http://dx.doi.org/10.1055/a-1266-3546DOI Listing
November 2020

Selective retina therapy (SRT) in patients with therapy refractory persistent acute central serous chorioretinopathy (CSC): 3 months functional and morphological results.

Graefes Arch Clin Exp Ophthalmol 2021 Jun 18;259(6):1401-1410. Epub 2020 Nov 18.

University Eye Hospital, Medical School Hannover, Carl-Neuberg-Str.1, 30625, Hannover, Germany.

Purpose: Central serous chorioretinopathy (CSC) is a disease presenting with detachment of the neurosensory retina and characteristic focal leakage on fluorescein angiography. The spontaneous remission rate is 84% within 6 months. In this study, the efficacy of selective retina therapy (SRT) was examined in patients with therapy refractory persistent acute CSC defined by symptoms for at least 6 months and persistent subretinal fluid (SRF) despite eplerenone therapy.

Material And Methods: This is a prospective, monocentric observational study in 17 eyes (16 patients, mean age 42 years, 2 female). SRT was performed with the approved R:GEN laser (Lutronic, South Korea), a micropulsed 527-nm Nd:YLF laser device, with a train of 30 pulses of 1.7 μs at 100-Hz repetition rate at the point of focal leakage determined by fluorescein angiography (FA) at baseline (BSL). Visits on BSL, week 4 (wk4), and week 12 (wk12) included best corrected visual acuity (BCVA, logMar), central retinal thickness (CRT) on spectral domain optical coherence tomography (SD-OCT), and FA. Statistical analysis was performed by pair-by-pair comparisons of multiple observations in each case with Bonferroni correction for multiple testing. (IBM SPSS Statistics 25®).

Results: Mean CRT at BSL was 387.69 ± 110.4 μm. CRT significantly decreased by 106.31 μm in wk4 (95%-KI: 21.42-191.2; p = 0.01), by 133.63 μm in wk12 (95%-KI: 50.22-217.03; p = 0.001) and by 133.81 μm (95%-KI: 48.88-218.75; p = 0.001) compared to BSL. Treatment success defined as complete resolution of SRF occurred at wk4 in 7/17 eyes (35.3%) and at wk12 in 10/17 eyes (58.8%). Re-SRT was performed in 7/17 eyes (41.2%) after an average of 107.14 ± 96.59 days. Treatment success after Re-SRT was observed in 4/6 eyes (66.6%, 12 weeks after Re-SRT). Mean BCVA did not change significantly from BSL to any later timepoint after adjusting for multiple testing. Notably, eyes with treatment success showed better BCVA at all timepoints and gained more letters compared to failures.

Conclusion: Single or repetitive SRT may be an effective and safe treatment in 2 of 3 patients suffering from acute persistent CSC after 6 months of symptoms or more. We observed complete resolution of SRF in around 60% of eyes 12 weeks after first SRT treatment and also 12 weeks after Re-SRT treatment in eyes with persistent or recurrent SRF. Results on the long-term course after SRT are still pending.
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http://dx.doi.org/10.1007/s00417-020-04999-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166675PMC
June 2021

[Bilateral posterior serous retinal detachment associated with HELLP syndrome].

Ophthalmologe 2021 Nov 4;118(11):1140-1142. Epub 2020 Nov 4.

Universitätsklinik für Augenheilkunde, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625, Hannover, Deutschland.

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http://dx.doi.org/10.1007/s00347-020-01257-5DOI Listing
November 2021

Postinfectious Onset of Myasthenia Gravis in a COVID-19 Patient.

Front Neurol 2020 6;11:576153. Epub 2020 Oct 6.

Department of Neurology, Hannover Medical School, Hanover, Germany.

We report the case of a young woman with postinfectious onset of myasthenia gravis after COVID-19 with mild respiratory symptoms and anosmia/ageusia 1 month before admission to our neurological department. Patient data were derived from medical records of Hannover Medical School, Germany. Written informed consent was obtained from the patient. The 21-year-old female patient presented with subacute, vertically shifted double vision evoked by right sided partial oculomotor paresis and ptosis. About 4 weeks earlier she had suffered from mild respiratory symptoms, aching limbs and head without fever, accompanied by anosmia/ageusia. During the persistence of the latter symptoms for around 10 days the patient had already noticed "tired eyes" and fluctuating double vision. Clinical assessment including a positive test with edrophonium chloride and increased acetylcholine receptor antibodies related the ocular manifestation etiologically to myasthenia gravis. Antibodies (IgA/IgG) against SARS-CoV-2 using three different serological tests (Abbott, DiaSorin, Euroimmun) were detected in serum suggesting this specific coronavirus as previously infectious agent in our patient. The myasthenic syndrome was treated successfully with intravenous immunoglobulins and oral pyridostigmine. This is the first case presentation of postinfectious myasthenia gravis as neurological complication in a COVID-19 patient.
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http://dx.doi.org/10.3389/fneur.2020.576153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7573137PMC
October 2020

The microRNAs miR-302d and miR-93 inhibit TGFB-mediated EMT and VEGFA secretion from ARPE-19 cells.

Exp Eye Res 2020 12 25;201:108258. Epub 2020 Sep 25.

Institute of Experimental Ophthalmology, University Eye Hospital, Hannover Medical School, Hannover, 30625, Germany.

The transforming growth factor-beta (TGFB) plays an essential role in the pathogenesis of some ophthalmologic diseases, including neovascular age-related macular degeneration (nAMD) and proliferative vitreoretinopathy (PVR). TGFB activates the transcription factors SMAD2 and SMAD3 via the TGFB receptor, which together activate several genes, including VEGFA. TGFB treated ARPE-19 cells show an increased proliferation rate and undergo epithelial to mesenchymal transition (EMT). Since microRNAs (miRNAs) are capable of inhibiting the translation of multiple genes, we screened for miRNAs that regulate the TGFB signalling pathways at multiple levels. In this study, we focused on two miRNAs, miR-302d and miR-93, which inhibit TGFB signalling pathway and therefore TGFB-induced EMT transition as well as VEGFA secretion from ARPE-19 cells. Furthermore, we could show that both miRNAs can retransform TGFB-stimulated mesenchymal ARPE-19 cells towards the morphological epithelial-like state. Taken together, transient overexpression of these miRNAs in RPE cells might be a promising approach for further translational strategies.
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http://dx.doi.org/10.1016/j.exer.2020.108258DOI Listing
December 2020

Importance of continuous treatment with intravitreal aflibercept injections in patients with neovascular age-related macular degeneration-12-month post hoc analysis of the PERSEUS real-world evidence study.

Graefes Arch Clin Exp Ophthalmol 2021 Mar 13;259(3):601-611. Epub 2020 Aug 13.

Klinik für Augenheilkunde, Medizinische Hochschule Hannover, Hannover, Germany.

Purpose: To investigate the influence of treatment regularity with intravitreal aflibercept injections (IVT-AFL injections) on visual acuity (VA) outcomes in patients with neovascular age-related macular degeneration (nAMD) enrolled in the PERSEUS trial who received at least 7 IVT-AFL injections during the first year.

Methods: This was a post hoc analysis of the PERSEUS trial, a prospective, non-interventional, multicenter cohort study, and included 370 patients with nAMD who had received ≥ 7 IVT-AFL injections during year 1. In addition to the prespecified subgroups of treatment-naïve and previously treated patients, results were compared between patients with regular (n = 209) and irregular (n = 161) treatment. Regular treatment was defined as initial dosing with monthly IVT-AFL injections for 3 months, then bimonthly IVT-AFL injections until month 12. Irregular treatment was defined as any deviation from regular treatment (provided ≥ 7 injections were received). The outcome of primary interest was the mean change in VA from baseline after 12 months. Further outcomes of interest included VA gain or loss, proportion of patients achieving reading vision, and percentage of patients with fluid.

Results: At month 12, the mean (± standard deviation, SD) VA improvement from baseline was 6.1 ± 15.6 Early Treatment Diabetic Retinopathy Study letters in the regular cohort and 2.5 ± 16.7 letters in the irregular cohort with ≥ 7 IVT-AFL injections (P = 0.0514). Best results were obtained in the treatment-naïve regular sub-cohort with a mean ± SD VA improvement of 8.0 ± 17.7 letters, whereas treatment-naïve patients with irregular treatment experienced a considerably lower VA gain (2.8 ± 20.0 letters). Irregular treatment consistently correlated with inferior results in treatment-naïve patients. At month 12, the proportion of treatment-naïve patients who had experienced a worsening of ≥ 5 letters was 29.6% in the irregular sub-cohort versus 13.6% in the regular sub-cohort (P = 0.0049). However, among the treatment-naïve patients, the mean number of injections was significantly higher in the irregular than in the regular sub-cohort (8.0 ± 1.2 vs. 7.4 ± 0.6; P = 0.0001). Furthermore, compared with the treatment-naïve, regular sub-cohort, patients in the irregular sub-cohort had more visits (19.1 ± 8.6 vs. 16.1 ± 5.7), VA tests (14.2 ± 6.9 vs. 12.0 ± 4.6), and optical coherence tomography examinations (5.1 ± 3.7 vs. 3.4.0 ± 3.0).

Conclusions: Although irregularly treated patients received more injections and more monitoring visits during the first year of IVT-AFL treatment, they experienced worse VA outcomes than regularly treated patients.
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http://dx.doi.org/10.1007/s00417-020-04803-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904558PMC
March 2021

Comparison of Macular Pigment Optical Density in Glaucoma Patients and Healthy Subjects - A Prospective Diagnostic Study.

Clin Ophthalmol 2020 1;14:1011-1017. Epub 2020 Apr 1.

University Eye Hospital, Hannover Medical School, Hannover 30625, Germany.

Purpose: To evaluate the relationship between macular pigment optical density (MPOD) and glaucoma.

Methods: Forty-three patients with an established glaucoma diagnosis (25 females, 18 males, mean age 70 (range 34-84)) and 43 healthy controls (28 females, 15 males, mean age 62 (range 30-87)) were included in this prospective diagnostic case-control study. All subjects underwent detailed eye examination including ophthalmoscopy, best-corrected visual acuity, biomicroscopy, measurement of the axial length of the eye, objective refraction, lens status, central foveal thickness on spectral-domain optical coherence tomography (SD-OCT). In all glaucoma patients, a visual field assessment and a measurement of the retinal nerve fibre layer (RNFL) on SD-OCT were done. MPOD was determined using the macula pigment module of the Spectralis HRA+OCT (Heidelberg Engineering GmbH, Heidelberg, Germany) at 0.51°, 1.02° and 1.99° retinal eccentricity using two-wavelength autofluorescence imaging.

Results: In the glaucoma group, the median of the visual field mean defect was 5.1 db (quartiles 3.0 and 13.5) and the mean RNFL-thickness global was 65.9 µm (SD ± 16.1). Median MPOD measured at 0.51°, 1.02° and 1.99° retinal eccentricity in the glaucoma group was 0.42 DU, 0.34 DU and 0.13 DU, in the control group 0.40 DU, 0.35 DU and 0.12 DU respectively. There was no statistically significant difference of median MPOD between glaucomatous and control eyes (p=0.510, 0.735, 0.481). No significant relation between MPOD at 1.02 retinal eccentricity and the presence of glare symptoms was found (p=0.948). However, age seems to correlate with median MPOD measured at 1.02 retinal eccentricity (p=0.017).

Conclusion: There was no evidence for lower MPOD levels in our glaucoma patients; lower MPOD was not related to the presence of glare symptoms. However there seems to be a positive correlation between age and MPOD at 1.02° retinal eccentricity. To further investigate the relation between glare reported by glaucoma patients and glare disability linked to lower MPOD levels, additional studies are necessary that include both detailed inquiry of the quality of glare and a glare quantification and precise analysis of MPOD levels in glaucoma patients.
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http://dx.doi.org/10.2147/OPTH.S224259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140904PMC
April 2020

Individualized treat-and-extend regime for optimization of real-world vision outcome and improved patients' persistence.

BMC Ophthalmol 2020 Mar 30;20(1):122. Epub 2020 Mar 30.

Hannover Medical School, University Eye Hospital, Carl-Neuberg-Straße 1, 30625, Hannover, Germany.

Background: Intravitreal injections are a mandatory treatment for macular edema due to nAMD, DME and RVO. These chronic diseases usually need chronic treatment using intravitreal injections with anti-VEGF agents. Thus, many trials were performed to define the best treatment interval using pro re nata regimes (PRN), fixed regimes or treat-and-extend regimes (TE). However, real-world studies reveal a high rate of losing patients within a 2-year interval of treatment observation causing worse results. In this study we analyzed retrospectively 2 years of real-world experience with an individualized treat-and-extend injection scheme.

Methods: Since 2015 our treatment scheme for intravitreal injections has been switched from PRN to TE. Out of 102 patients 59 completed a follow up time of 2 years. Every patient received visual acuity testing, SD-OCT and slit lamp examination prior to every injection. At each visit an injection was performed and the treatment interval was adjusted mainly on SD-OCT based morphologic changes by increasing or reducing in 2-week steps. Individual changes of the treatment protocol by face-to-face communication between physician and patient were possible.

Results: After 1 year of treatment visual acuity gain in nAMD was 7.4 ± 2.2 ETDRS letters (n = 34; injection frequency: 7.4 ± 0.4) respectively 6.1 ± 4.7 in DME (n = 9; injection frequency: 8.4 ± 1.1) and 9.7 ± 4.5 in RVO (n = 16; injection frequency: 7.6 ± 0.5). After 2 years of treatment results were as following: nAMD: visual acuity gain 6.9 ± 2.1 (injection frequency: 12.6 ± 0.7); DME: 11.1 ± 5.1 (injection frequency: 14.0 ± 1.0); RVO: 7.5 ± 5.0 (injection frequency: 11.2 ± 0.9). Planned treatment exit after 2 year was achieved in 29.4% of patients in nAMD (0% after 1 year); 0% in DME (0% after 1 year); and 31.3% in RVO (0% after 1 year). Patients' persistence was 94.1% during the follow-up.

Conclusion: Using a consequent and individualized TE regime in daily practice may lead to a high patients' persistence and visual acuity gains nearly comparable to those of large prospective clinical trials. Crucial factors are face-to-face communication with the patient as well as a stringent management regime. At this time TE may be the only instrument for proactive therapy which should therefore be regarded as a first-line tool in daily practice.
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http://dx.doi.org/10.1186/s12886-020-01397-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7104494PMC
March 2020

Neuroprotection with rasagiline in patients with macula-off retinal detachment: A randomized controlled pilot study.

Sci Rep 2020 03 18;10(1):4948. Epub 2020 Mar 18.

Department of Ophthalmology and Department of Clinical Research, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.

We aimed to evaluate the neuroprotective efficacy of rasagiline in pseudophakic patients who had surgery for macula-off rhegmatogenous retinal detachment (RRD). This was a 6-month, prospective, randomized, double-blind, placebo-controlled pilot study. Patients presenting with acute macula-off RRD were recruited and randomized 1:1 to receive rasagiline 1 mg/day or placebo for 7 days. Best-corrected visual acuity (BCVA) and optical coherence tomography were acquired 1 day before as well as 2 days, 3 weeks, 3 months and 6 months after surgery. We screened 26 patients with RRD whereof 23 were eventually included and randomized. The primary outcome was final BCVA. Secondary outcomes included central retinal thickness (CRT) and adverse events (AE). We evaluated photoreceptor cells (prc) recovery through morphological measurements. The baseline characteristics were comparable between groups. BCVA significantly improved in both groups (letters gained: rasagiline 61.5 ± 18.1 vs placebo 55.3 ± 29.2, p = 0.56), but no significant inter-group difference was found at any visit. CRT was stable 3 weeks after surgery onwards, with no inter-group difference. No treatment-emergent AE occurred. Significant prc restoration was observed from 3 weeks to 6 months after surgery, without inter-group difference at either visit. Ellipsoid zone integrity (β = 0.517, p = 0.008) and foveal bulge (β = 0.387, p = 0.038) were significant predictors of good final BCVA. In conclusion, perioperative oral treatment with rasagiline 1 mg/day for 7 days did not show significant benefits on visual or anatomical outcomes in macula-off RRD patients.
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http://dx.doi.org/10.1038/s41598-020-61835-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7080767PMC
March 2020

[Retinal laser treatment-avoiding mistakes].

Ophthalmologe 2020 Feb;117(2):169-188

Universitäts-Augenklinik, Göttingen, Deutschland.

Even in the era of intravitreal injection therapy (intravitreal operative injection of medication, IVOM) for the treatment of macular and retinal diseases, such as age-related macular degeneration (AMD), proliferative diabetic retinopathy (DR) and diabetic macular edema (DME) as well as proliferative stages and/or macular edema due to retinal vein occlusion (RVO), conventional retinal laser treatment is still of importance. It can be focally performed on an on-label basis for DME and macular edema due to branch RVO (BRVO) and its use as panretinal treatment for proliferative stages in retinal diseases as well as for the treatment of retinal holes is undisputed. The spectrum is extended by the treatment of less common diseases, such as retinal hemangioblastoma, macroaneurysms and subhyaloid macular hemorrhage. There is cause for concern that knowledge about the correct performance of retinal laser application might be shifted into the background due to an increase of IVOM treatment, which could lead to an increase in unnecessary errors. The aim of this manuscript is to increase awareness for the correct indications and execution of retinal laser treatment based on case examples of flawed or insufficient treatment.
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http://dx.doi.org/10.1007/s00347-019-01035-yDOI Listing
February 2020

How and why SGLT2 inhibitors should be explored as potential treatment option in diabetic retinopathy: clinical concept and methodology.

Ther Adv Endocrinol Metab 2019 11;10:2042018819891886. Epub 2019 Dec 11.

MHH Clinical Research Center Core Facility (OE 8660) and Center for Pharmacology and Toxicology, Hannover, Germany.

Patients suffering from type 2 diabetes are at an increased risk of developing classical microvascular complications such as retinopathy, neuropathy, and nephropathy, which represent a significant health burden. Tight control of blood glucose, blood pressure, and serum cholesterol reduce the risk of microvascular complications but effective pharmacologically targeted treatment options for the treatment and prevention of diabetic microangiopathy are still lacking. Pharmacological inhibition of sodium glucose cotransporter 2 (SGLT2) might have the potential to directly protect against microvascular complications and could represent a potential treatment option. Randomized controlled clinical proof of concept trials are needed to investigate a potential central role of SGLT2 inhibitors in the prevention of diabetic microangiopathy and its classical clinical complications of retinopathy, neuropathy, and nephropathy.
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http://dx.doi.org/10.1177/2042018819891886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6906337PMC
December 2019

Ipsilateral transient amaurosis, mydriasis and light reflex absence after subconjunctival local anesthesia with mepivacaine in three patients with refractory glaucoma - a case report.

BMC Ophthalmol 2019 Aug 28;19(1):195. Epub 2019 Aug 28.

Department of Ophthalmology, University Eye Hospital, Hannover Medical School, Carl-Neuberg-Str.1, 30625, Hannover, Germany.

Background: The subconjunctival anesthesia with local anesthetics is considered as a low-risk procedure allowing ocular surgery without serious complications typical for retro- or parabulbar anesthesia, especially in patients with preexisting Optic Nerve damage. We report development of ipsilateral transient amaurosis accompanied with mydriasis and both, direct and consensual light response absence.

Case Presentation: Three patients with advanced refractory glaucoma undergoing laser cyclophotocoagulation (CPC) for intraocular pressure lowering experienced these adverse effects just few minutes after subconjunctival injection of mepivacaine 2% solution (Scandicaine® 2%, without vasoconstrictor supplementation). The vision was completely recovered to usual values in up to 20 h after mepivacaine application. Extensive ophthalmological examination, including cranial magnetic resonance imaging (MRI), revealed no further ocular abnormalities, especially no vascular constriction or thrombotic signs as well as no retinal detachment. The oculomotor function remained intact. The blockade of ipsilateral ciliary ganglion parasympathetic fibers by mepivacaine may be the responsible mechanism. Systemic pathways as drug-drug interactions seem to be unlikely involved. Importantly, all three patients tolerated the same procedure previously or at a later date without any complication. Overall, our thoroughly elaborated risk management could not determine the causative factor explaining the observed ocular complications just in the current occasion and not at other time points.

Conclusions: Doctors should be aware and patients should be informed about such rare complications after subconjunctival local anesthetics administration. Adequate risk management should insure patients' safety.
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http://dx.doi.org/10.1186/s12886-019-1202-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6712733PMC
August 2019

Aflibercept for Patients with Neovascular Age-Related Macular Degeneration in Routine Clinical Practice in Germany: Twelve-Month Outcomes of PERSEUS.

Ophthalmol Retina 2018 06 20;2(6):539-549. Epub 2017 Nov 20.

Abteilung für Augenheilkunde, Sankt Gertrauden-Krankenhaus, Berlin, Germany.

Purpose: To explore real-world effectiveness of intravitreal aflibercept injection (IAI) for neovascular age-related macular degeneration (nAMD) in Germany.

Design: A 24-month, prospective, noninterventional, noncontrolled, multicenter observational cohort study.

Participants: Patients (n = 848) with nAMD treated with IAI.

Methods: Patients (n = 988) were screened at 67 study sites. Therapeutic decisions were made by the treating physician. Primary end point analysis was performed after 12 months for the entire study cohort and for predetermined subgroups of treatment-naïve and previously treated patients. Additionally, outcomes with regular injection intervals (bimonthly after 3 monthly injections) were compared with those of patients with irregularities in their treatment regimen.

Main Outcome Measures: The primary end point was the mean change in visual acuity (VA) from baseline after 12 months. Other key end points included the proportions of patients gaining 15 letters or more and patients with reading vision (≥70 letters). Furthermore, the number of injections, anatomic measurements, and safety data were recorded.

Results: Mean ± standard deviation VA improvement was 5.3±17.4 letters in treatment-naïve patients and -0.1±15.6 letters in previously treated patients (P ≤ 0.0001), and that of the total study group was 2.9±16.8 letters. Baseline VA was 53.4±17.9 letters for treatment-naïve patients, 52.9±18.4 letters for previously treated patients, and 53.2±18.1 letters for the total patient population. Treatment pattern was associated with VA outcome: best outcomes-an average VA gain of 8.0±17.7 letters-were seen in treatment-naïve patients in the regularly treated population, whereas irregularly treated, treatment-naïve patients achieved a mean VA gain of only 4.0±17.1 letters. Among previously treated patients, regular treatment also was associated with better outcomes (+3.1±10.7 vs. -1.1±16.8 letters). For the total study group, the mean VA gain was the following: regularly treated population, 6.1±15.6 letters; irregularly treated population, 1.5±17.1 letters (P = 0.008). No cases of endophthalmitis were observed during the first 12 months of the study. Adverse events were in line with the known safety profile of IAI.

Conclusions: After 12 months of treatment with IAI, treatment-naïve patients showed substantial functional benefit, whereas previously treated patients maintained their VA. With regular IAI treatment, it seems that similar results as those in pivotal IAI studies can be achieved in routine clinical practice.
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http://dx.doi.org/10.1016/j.oret.2017.09.017DOI Listing
June 2018

Selective retina therapy: toward an optically controlled automatic dosing.

J Biomed Opt 2018 11;23(11):1-12

Medizinisches Laserzentrum Lübeck GmbH, Lübeck, Germany.

Selective retina therapy (SRT) targets the retinal pigment epithelium (RPE) with pulsed laser irradiation by inducing microbubble formation (MBF) at the intracellular melanin granula, which leads to selective cell disruption. The following wound healing process rejuvenates the chorio-retinal junction. Pulse energy thresholds for selective RPE effects vary intra- and interindividually. We present the evaluation of an algorithm that processes backscattered treatment light to detect MBF as an indicator of RPE cell damage since these RPE lesions are invisible during treatment. Eleven patients with central serous chorioretinopathy and four with diabetic macula edema were treated with a SRT system, which uses a wavelength of 527 nm, a repetition rate of 100 Hz, and a pulse duration of 1.7 μs. Fifteen laser pulses with stepwise increasing pulse energy were applied per treatment spot. Overall, 4626 pulses were used for algorithm parameter optimization and testing. Sensitivity and specificity were the metrics maximized through an automatic optimization process. Data were verified by fluorescein angiography. A sensitivity of 1 and a specificity of 0.93 were achieved. The method introduced in this paper can be used for guidance or automatization of microbubble-related treatments like SRT or selective laser trabeculoplasty.
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http://dx.doi.org/10.1117/1.JBO.23.11.115002DOI Listing
November 2018

Ocular Blood Volume Index Based on Scattering Properties of Retinal Vessels Using Spectral Domain Optical Coherence Tomography.

Curr Eye Res 2019 01 15;44(1):60-66. Epub 2018 Oct 15.

b University Eye Clinic , Hannover Medical School , Hannover , Germany.

The evaluation of retinal vessels and the retinal blood flow is important for ocular diseases. We introduce a spectral domain optical coherence tomography (SD-OCT) based method for facilitating a retinal blood vessel analysis using the scattering properties of retinal vessels. The intensity of the distal shadow of vessels caused by the scattered signal is measured, correlated with the pulsatile ocular blood flow (POBF), and its repeatability is analyzed. About 20 eyes of 20 healthy, young participants (mean age 23.15 years, standard deviation 2.3 years) were included in the analysis. Participants underwent ophthalmic diagnostics including three repeated SD-OCT examinations and measurement of POBF. The vessel shadow intensity analysis is based on peripapillary SD-OCT scans and automatically analyses the intensity of the distal vessel shadow compared to its surroundings. The distal shadow of arteries in SD-OCT scans correlated with the POBF ( = 0.647,  = 0.002). Furthermore, the shadow intensity correlated with the established morphological arterio-venous ratio. The evaluation of repeatability was performed using the interclass correlation coefficient (ICC), showing good repeatability for individual vessels (ICC = 0.825) and arteries (ICC = 0.820). In summary, we indicate that the scattering properties of retinal vessels in SD-OCT images might correlate with the vessel morphology and for retinal arteries with the retinal blood flow volume as well. Further studies are needed to establish this method's sensitivity and specificity in participants with retinal and cardiovascular diseases.
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http://dx.doi.org/10.1080/02713683.2018.1527367DOI Listing
January 2019

Optical coherence tomography angiography analysis of macular flow density in glaucoma.

Acta Ophthalmol 2019 Mar 4;97(2):e199-e206. Epub 2018 Sep 4.

Hannover Medical School, University Eye Hospital, Hannover, Germany.

Purpose: Modifications in ocular blood flow may play a significant role in glaucoma development. Optical coherence tomography angiography (OCT-A) is based on the detection and analysis of the reflection behaviour of motion in a static environment and therefore is able to quantify the retinal flow density. We used this new technology to examine the density of the active flow vasculature in the macular area in glaucoma patients compared to healthy patients.

Methods: Thirty patients with primary open-angle glaucoma (mean age: 72.6 ± 7.1 years) and 21 healthy patients (mean age: 70.3 ± 8.6 years) were recruited. Patients received perimetry and OCT measurements of the peripapillary retinal nerve fibre layer thickness (RNFLT) and macular retinal thickness and OCT-A of the macular area in the superficial and deep retinal (DR) plexus. Flow density of the OCT-A scan was calculated by binarisation and quantification of the pixel density.

Results: Macular flow density was globally and nasally reduced in glaucoma patients in the superficial (globally: p = 0.0203; nasally: p = 0.0003) and DR plexus (globally: p = 0.0113, nasally: p < 0.0001). There was no significant difference between the superficial retina and the DR concerning the flow density. Flow density showed no significant correlation with perimetry results, RNFLT or retinal segment thickness.

Conclusion: Patients with glaucoma exhibit a reduced macular flow density measured by OCT-A compared to controls. The independence of the macular flow density of the retinal segment thickness changes could indicate an altered vascular element in patients with glaucoma.
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http://dx.doi.org/10.1111/aos.13914DOI Listing
March 2019

Intraoperative optical coherence tomography and ab interno trabecular meshwork surgery with the Trabectome.

Clin Ophthalmol 2017 28;11:1755-1760. Epub 2017 Sep 28.

University Eye Hospital, Medical School Hannover, Hannover.

Importance: This study is the first description of the use of the intraoperative optical coherence tomography (iOCT) for trabecular meshwork surgery with the Trabectome in a regular clinical setting.

Background: The aim of this study is to evaluate intraoperatively the immediate success of ab interno trabeculotomy with the Trabectome defined as a removal of the trabecular meshwork.

Design: This is a retrospective clinical study performed in the University Eye Hospital, Medical School Hannover.

Participants: A total of nine consecutive Caucasian patients suffering from primary open angle glaucoma, pigment dispersion glaucoma, or pseudoexfoliation glaucoma took part in the study.

Methods: All patients underwent ab interno trabeculotomy surgery with the Trabectome using a commercially available iOCT to visualize the anterior chamber angle (ACA) before and after the procedure. The visualization was done using a modified Swan-Jacobs lens (all nine patients) or without lens (view from above, five patients).

Main Outcome Measures: The main outcome of this study is the success of visualization of the ACA on iOCT, especially the postprocedural visualization of the wound gap after removal of the trabecular meshwork.

Results: Using the view from above, the ACA could be visualized before and after the procedure in only two of the five cases. Using the modified Swan-Jacobs lens, the ACA could be visualized before the procedure and the trabecular meshwork opening after the procedure in all nine patients.

Conclusion: The iOCT can be used to objectify the immediate success of the surgical procedure, ie, the removal of the trabecular meshwork, of ab interno trabeculotomy with the Trabectome. The procedure itself cannot be captured sufficiently via iOCT.
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http://dx.doi.org/10.2147/OPTH.S145873DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5627725PMC
September 2017

[Intraoperative Optical Coherence Tomography in Vitreoretinal Surgery: Clinical Experiences and Future Developments].

Klin Monbl Augenheilkd 2018 Sep 9;235(9):1028-1034. Epub 2017 Jun 9.

Klinik für Augenheilkunde, Klinikum Ludwigshafen.

Purpose: High resolution optical coherence tomography (OCT) enables better visualization of ophthalmic microstructures than conventional imaging. When using an ophthalmic microscope, integrated optical coherence tomography (iOCT) high resolution real time visualization is possible.

Methods: We report on the first 110 patients operated on using a microscope integrated OCT (iOCT) during surgical procedures for the treatment of various posterior segment pathologies.

Results: Microstructural changes that appeared during surgery were depicted precisely by iOCT, and the morphology visualized before and after each surgical step was used to help deciding how to adapt the surgical flow. The iOCT data and real-time imaging of retinal anatomy gives the surgeon the possibility of deploying patient- and operation-specific interventional procedures.

Discussion: To date, iOCT is only available in standing microscopes with no measurement or tracking features. Moreover, metal instruments currently obscure the scanned images. In the future, non-metal, transparent instruments (OCT-friendly surgical tools), tracking features, an autofocus and higher resolution could enable full and immediate intraoperative SD-OCT diagnostics in real time.
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http://dx.doi.org/10.1055/s-0043-106304DOI Listing
September 2018

Author's reply to comments to: Visual and anatomic outcomes after conversion to aflibercept in neovascular age-related macular degeneration: 12-month results.

Eur J Ophthalmol 2017 06 26;27(4):e135. Epub 2017 Jun 26.

University Eye Hospital, Hannover Medical School, Hannover - Germany.

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http://dx.doi.org/10.5301/ejo.5000981DOI Listing
June 2017

Listeria monocytogenes endophthalmitis - case report and review of risk factors and treatment outcomes.

BMC Infect Dis 2016 Jul 16;16:332. Epub 2016 Jul 16.

Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany.

Background: The majority of cases of endophthalmitis are caused by exogenous pathogens; only 5-10 % are of endogenous origin. One cause of these rare cases of endogenous endophthalmitis is Listeria monocytogenes. Twenty-six cases of endophthalmitis due to this pathogen have been published over the last twenty years. The aim of this review is to summarize the main risk factors and common clinical findings of endogenous endophthalmitis due to Listeria monocytogenes.

Case Presentation: We report on a 62-year-old female presenting with a sterile hypopyon iritis with secondary glaucoma and an underlying rheumatoid disease. In microbiological analysis we identified Listeria monocytogenes. Further we searched through all published cases for typical signs, risk factors, details of medical and surgical treatment and outcome of endogenous endophthalmitis due to this rare pathogen. Ocular symptoms in almost all of these published cases included pain, redness of the eye, and decreased vision. Main clinical features included elevated intraocular pressure and fibrinous anterior chamber reaction, as well as a dark hypopyon. While the infection is typically spread endogenously, neither an exogenous nor endogenous source of infection could be identified in most cases. Immunocompromised patients are at higher risk of being infected than immunocompetent patients. The clinical course of endophthalmitis caused by Listeria monocytogenes had different visual outcomes. In some cases, the infection led to enucleation, blindness, or strong visual loss, whereas most patients showed a tendency of visual improvement during therapy.

Conclusion: Early diagnosis and treatment initiation are crucial factors in the outcome of endogenous endophthalmitis caused by Listeria monocytogenes. This possible differential diagnosis should be kept in mind while treating patients with presumable sterile hypopyon and anterior uveitis having a high intraocular pressure. A bacterial source should be considered with a prompt initiation of systemic antibiotic treatment, mainly in immunocompromised patients, who develop endogenous anterior uveitis. An appropriate microbiological sampling is essential to detect atypical microorganisms and to choose an effective antibiotic treatment.
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http://dx.doi.org/10.1186/s12879-016-1680-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4947317PMC
July 2016

Peripheral retinal non-perfusion and treatment response in branch retinal vein occlusion.

Int J Ophthalmol 2016 18;9(6):858-62. Epub 2016 Jun 18.

Department of Ophthalmology, University Eye Hospital, Medical School of Hannover, Carl-Neuberg-Straße 1, Hannover 30625, Germany; Department of Ophthalmology, Ludwig Maximilians University, Mathildenstr. 8, Munich 80336, Germany.

Aim: To evaluate the association between the size of peripheral retinal non-perfusion and the number of intravitreal ranibizumab injections in patients with treatment-naive branch retinal vein occlusion (BRVO) and macular edema.

Methods: A total of 53 patients with treatment-naive BRVO and macular edema were included. Each patient underwent a full ophthalmologic examination including optical coherence tomography (OCT) imaging and ultra wide-field fluorescein angiography (UWFA). Monthly intravitreal ranibizumab injections were applied according to the recommendations of the German Ophthalmological Society. Two independent, masked graders quantified the areas of peripheral retinal non-perfusion.

Results: Intravitreal injections improved best-corrected visual acuity (BCVA) significantly from 22.23±16.33 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters to 36.23±15.19 letters (P<0.001), and mean central subfield thickness significantly reduced from 387±115 µm to 321±115 µm (P=0.01). Mean number of intravitreal ranibizumab injections was 3.61±1.56. The size of retinal non-perfusion correlated significantly with the number of intravitreal ranibizumab injections (R=0.724, P<0.001).

Conclusion: Peripheral retinal non-perfusion in patients with BRVO associates significantly with intravitreal ranibizumab injections in patients with BRVO and macular edema.
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http://dx.doi.org/10.18240/ijo.2016.06.12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4916143PMC
July 2016

The short-term effects of aflibercept on the size of choroidal neovascularization lesion in treatment-resistant neovascular age-related macular degeneration as determined by spectral-domain optical coherence tomography.

Lasers Surg Med 2016 09 25;48(7):668-77. Epub 2016 Apr 25.

Department of Ophthalmology, University Eye Hospital, Hannover Medical School, Hannover, Germany.

Background And Objectives: To evaluate the changes in the size of choroidal neovascularization (CNV) lesion using spectral domain-optical coherence tomography (SD-OCT) in patients with treatment-resistant neovascular age-related macular degeneration (AMD) who were switched from ranibizumab to aflibercept.

Materials And Methods: In this prospective case-series, 33 eyes of 30 patients with treatment-resistant neovascular AMD were included. Treatment-resistant neovascular AMD was defined as choriodal neovascularization secondary to AMD determined by subretinal fluid and/or intraretinal fluid/cysts after more than 6 months of monthly ranibizumab therapy. Enrolled eyes were received intravitreal aflibercept injections at weeks 0, 4, and 8. Maximum area of CNV lesion in the cross-sectional area in the B-scan was measured using Heidelberg Eye Explorer software. The same cross-sectional sections containing maximum area of CNV lesion were used during the follow-up. CNV subtypes were determined based on fluorescein angiography images prior to ranibizumab therapy. Main outcome measures were changes in best-corrected visual acuity (BCVA), central subfield thickness (CST), and area of CNV lesion.

Results: There were five classic (15%), seven minimally classic (21%), and 21 occult subtypes of CNV (64%). Four weeks after the third injection, BCVA improvement and reduction of the retinal thickness in nine standard ETDRS subfields were significant (both P < 0.001). Regarding and regardless of CNV subtypes, mean area of CNV lesion decreased significantly at final visit. Overall, a dry macula was achieved in 21 eyes (64%) and 12 eyes (36%) showed decreased or unchanged edema.

Conclusions: Switching to aflibercept seems to result in reduction of CNV lesion area in short-term follow-up of patients with treatment-resistant neovascular AMD. Lasers Surg. Med. 48:668-677, 2016. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/lsm.22531DOI Listing
September 2016

Visual and anatomic outcomes after conversion to aflibercept in neovascular age-related macular degeneration: 12-month results.

Eur J Ophthalmol 2016 Aug 5;26(5):473-8. Epub 2016 Feb 5.

Department of Ophthalmology, University Eye Hospital, Hannover Medical School, Hannover - Germany.

Purpose: To investigate 12-month outcomes of conversion to aflibercept in patients with neovascular age-related macular degeneration resistant to ranibizumab.

Methods: Twenty-two eyes of 19 consecutive patients received 3 monthly aflibercept injections followed by a pro re nata protocol. Spectral-domain optical coherence tomography (OCT) images were obtained before each injection. All 49 cross-sectional OCT B-scans obtained in each examination were investigated and the largest choroidal neovascularization (CNV) size was chosen. The same cross-sectional B-scan sections containing the maximum CNV size were used during the follow-up.

Results: After 12 months, best-corrected visual acuity increased from 45.68 ± 20.25 to 59.09 ± 17.50 Early Treatment Diabetic Retinopathy Study letters (p<0.001), central subfield thickness decreased from 399.91 ± 148.85 to 304.55 ± 97.89 μm (p = 0.003), area of CNV declined from 0.38 ± 0.24 to 0.28 ± 0.19 mm2 (p = 0.003), and macular volume improved from 9.64 ± 1.75 to 8.45 ± 0.98 mm3 (p<0.001). There was a significant resolution of intraretinal fluid (p = 0.016), but reduction of subretinal fluid was not significant (p = 0.25).

Conclusions: Visual and anatomic improvement were obtained after conversion to aflibercept.
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http://dx.doi.org/10.5301/ejo.5000757DOI Listing
August 2016

Time-Resolved Ultra-High Resolution Optical Coherence Tomography for Real-Time Monitoring of Selective Retina Therapy.

Invest Ophthalmol Vis Sci 2015 Oct;56(11):6654-62

ARTORG Center, University of Bern, Bern, Switzerland 3Department of Ophthalmology, Inselspital, Bern, Switzerland.

Purpose: Selective retina therapy (SRT) is a novel treatment for retinal pathologies, solely targeting the RPE. During SRT, the detection of an immediate tissue reaction is challenging, as tissue effects remain limited to intracellular RPE photodisruption. Time-resolved ultra-high axial resolution optical coherence tomography (OCT) is thus evaluated for the monitoring of dynamic optical changes at and around the RPE during SRT.

Methods: An experimental OCT system with an ultra-high axial resolution of 1.78 μm was combined with an SRT system and time-resolved OCT M-scans of the target area were recorded from four patients undergoing SRT. Optical coherence tomography scans were analyzed and OCT morphology was correlated with findings in fluorescein angiography, fundus photography, and cross-sectional OCT.

Results: In cases in which the irradiation caused RPE damage proven by fluorescein angiography, the lesions were well discernible in time-resolved OCT images but remained invisible in fundus photography and cross-sectional OCT acquired after treatment. If RPE damage was introduced, all applied SRT pulses led to detectable signal changes in the time-resolved OCT images. The extent of optical signal variation seen in the OCT data appeared to scale with the applied SRT pulse energy.

Conclusions: The first clinical results proved that successful SRT irradiation induces detectable changes in the OCT M-scan signal while it remains invisible in conventional ophthalmoscopic imaging. Thus, real-time high-resolution OCT is a promising modality to monitor and analyze tissue effects introduced by selective retina therapy and may be used to guide SRT in an automatic feedback mode (www.swissmedic.ch number, 2011-MD-0006).
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http://dx.doi.org/10.1167/iovs.15-17151DOI Listing
October 2015
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