QUANTITATIVE AUTOFLUORESCENCE IN CENTRAL SEROUS CHORIORETINOPATHY.

BACKGROUND/PURPOSE: Central serous chorioretinopathy (CSC) is associated with pachychoroid and dysfunctional retinal pigment epithelium. Autofluorescence (AF) is typically altered. The authors performed this study to quantify these alterations using quantitative AF (qAF) in patients with CSC and in their fellow eye in comparison with a healthy control group. METHODS: Patients with CSC and healthy controls were recruited prospectively. All patients received a full clinical examination including best-corrected visual acuity, enhanced depth imaging-optical coherence tomography, and qAF. Quantitative autofluorescence images were taken with a confocal scanning laser ophthalmoscope (Heidelberg Engineering). Quantitative autofluorescence values were assessed in specified regions of the inner eight and the middle ring of the Delori grid. RESULTS: In total, 141 eyes of 77 patients with CSC were included. Ninety eyes had a manifest CSC (group 1) while 51 fellow eyes (group 2) did not show signs of CSC. There were no significant differences of qAF values between these two groups: mean qAF values were 241.3 (inner eight) and 212.8 (middle ring) in group 1 and 235.9 (inner eight) and 210.0 (middle ring) in group 2 ( P = 1.0 and 1.0). We compared these eyes with healthy controls comprising 39 eyes. Quantitative autofluorescence signals (inner eight: 164.7; middle ring: 148.9) differed significantly compared with both CSC manifest ( P < 0.001) and fellow eyes ( P < 0.001). CONCLUSION: Our results show that patients with CSC have increased qAF values in both eyes with manifest CSC and asymptomatic, clinically unremarkable fellow eyes in comparison with healthy controls. This finding suggests that qAF alterations are present even before clinical signs can be observed.

Antiplatelet and anticoagulant therapy in patients with submacular hemorrhage caused by neovascular age-related macular degeneration.

PURPOSE: Patients with extensive submacular hemorrhage (SMH) caused by age-related macular degeneration (AMD) have a poor visual prognosis despite surgical intervention. Systemic blood-thinning drugs, which are commonly prescribed in the same age group, are known to increase the risk of severe hemorrhage in many parts of the body. This study aimed to investigate whether systemic blood-thinning drugs have an impact on the severity of SMH and if there are differences between the different types of blood-thinning medication. METHODS: We reviewed the medical records of patients who suffered from surgically treated SMH between 2020 and 2022. All patients received a full ophthalmologic examination upon presentation including best-corrected visual acuity (BCVA) and optical coherence tomography. Other characteristics that were recorded included size of hemorrhage, blood-thinning therapy, and reason for intake. RESULTS: A total of 115 patients with a mean age of 82 years were included in this retrospective analysis. Eighty-three patients (72.2%) were on blood-thinning therapy. The mean size of SMH was 32.01 mm2. Mean BCVA at initial presentation was 1.63 logMAR and 1.59 logMAR 1 year after surgery. The size of SMH was significantly larger in patients on blood-thinning medication (35.92 mm2 vs. 21.91 mm2) (p = 0.001) and their BCVA postoperatively was worse with 1.68 logMAR compared to 1.30 logMAR after 1 year (p = 0.503). Patients with vitamin K antagonists had larger SMH size and worse outcomes regarding BCVA compared to direct oral anticoagulants. CONCLUSION: Blood thinners in patients with AMD affect the severity of SMH. Consequently, the indication for their intake should be critically evaluated.

Clinical outcomes of the PAUL® glaucoma implant: One-year results.

BACKGROUND: To report one-year outcomes from a single-centre cohort undergoing PAUL® Glaucoma Implant (PGI) surgery. METHODS: Retrospective review of patients undergoing PGI surgery at the University Eye Hospital Bonn, Germany, from April 2021 to September 2021. RESULTS: Forty-five eyes of 41 patients were included. Qualified and complete success rates (95% CI) were 95.6% (88.9%-100%) and 73.3% (60%-86.7%) for Criterion A (IOP ≤ 21 mmHg), 84.4% (73.3%-93.3%) and 74.4% (51.1%-80.0%) for Criterion B (IOP ≤ 18 mmHg), 62.2% (48.9%-75.6%) and 46.7% (31.2%-62.2%) for Criterion C (IOP ≤ 15 mmHg) and 26.7% (13.3%-40.0%) and 22.2% (11.1%-33.3%) for Criterion D (IOP ≤ 12 mmHg), respectively. Mean IOP decreased from 26.1 mmHg (7-48 mmHg) to 12.0 mmHg (3-24 mmHg) (reduction of 48.83%) after 12 months with a reduction of IOP-lowering agents from 0.5 (0-3). One eye (2.2%) needed an injection of viscoelastic due to significant hypotony with AC shallowing, and four eyes (8.9%) developed choroidal detachments due to hypotony which resolved without further interventions after 6 weeks. Three patients (6.7%) developed tube exposure which required conjunctival revision with an additional pericardial patch graft. An intraluminal prolene stent was removed in 19 eyes (42.2%) after a mean time period of 8.4 months (2-12 m). Mean IOP before the removal was 21.9 mmHg (12-38 mmHg) and decreased to 11.3 mmHg (6-16 mmHg). CONCLUSIONS: PGI surgery is an effective procedure for reducing IOP and pressure-lowering therapy. An intraluminal prolene stent impedes hypotony in the early postoperative phase and enables further IOP lowering without additional interventions during the postoperative course.

Pars-plana-vitrectomy for endophthalmitis treatment and the role of standardized ultrasound.

PURPOSE: Endophthalmitis is a severe inflammation following surgery or endogenous spread of pathogens. Besides clinical signs and symptoms, standardized ultrasound might help to confirm the diagnosis. Thus, we analyzed 172 cases of endophthalmitis for pathogens, visual acuity (VA) and the predictive value of standardized ultrasound. METHODS: Retrospective analysis of patients treated with pars-plana-vitrectomy for endophthalmitis at the University Eye Hospital was performed. Sex, age, VA at presentation, first day after surgery, four weeks postoperatively, and at last follow-up, as well as pathogen culture, and presence of standardized ultrasound before vitrectomy were recorded. Mann-Whitney U and Chi-square tests were used for groupwise comparisons. RESULTS: A total of 172 patients (male = 47.7%) with a median age of 76 years (IQR 65-82 years) treated for endophthalmitis (exogenous = 85.5%) were included. Median follow-up time was 65 days (IQR 12-274 days). Visual acuity at presentation was 2.30 logMAR (IQR 2.70-2.30 logMAR); it increased to 1.00 logMAR (1.4-0.40 logMAR) at last follow-up. A total of 79 patients (45.9%) underwent standardized ultrasound before vitrectomy. Patients with positive ultrasound criteria had a significantly decreased VA at presentation (p = 0.034). Positive microbiological cultures for Streptococcus spp. and Enterococcus faecalis were associated with decreased VA (p = 0.028) at last follow-up. CONCLUSION: Standardized ultrasound is an easy and robust tool in the diagnosis of endophthalmitis. Positive criteria are significantly associated with decreased VA at presentation. The recovery of VA depends on pathogens and is significantly worse for certain species (Streptococcus spp., Enterococcus faecalis).

LONG-TERM EFFICACY OF FLUOCINOLONE IN EYES WITH IRIS-LENS DIAPHRAGM DISRUPTION AND PCME WITH MEDICATION FIXED IN THE SCLERA (MEFISTO).

PURPOSE: The aim of our prospective off-label, interventional clinical trial was to evaluate the efficacy and safety of the fluocinolone-loop-anchoring technique over two years in eyes with iris-lens diaphragm disruption and pseudophakic cystoid macular edema. METHODS: In 10 eyes, scleral fixation of fluocinolone implant was performed. Main outcome measures were the development of best-corrected visual acuity (BCVA), central retinal thickness over 24 months, and general safety of the procedure. RESULTS: A significant improvement to 0.57 ± 0.38 log MAR (Snellen 20/80) (range 0-1.30) was observed (P = 0.003) at 1 month. Further improvement to 0.45 ± 036 log MAR (Snellen 20/60) was observed until month 18 (P = 0.081). Mean central retinal thickness decreased by 22% from 601.6 ± 235.5 µm to 449.1 ± 128.9 µm at 1 month. In one patient, the implant has to be removed at Month 7 because of elevated intraocular pressure and one patient after globe rupture had a retinal redetachment at Month 4. CONCLUSION: In this study, we showed that the treatment of recalcitrant pseudophakic cystoid macular edema with scleral fixated fluocinolone implant in eyes with disruption of the iris-lens diaphragm provides good anatomical and functional results with a reasonable safety profile over 24 months in eyes where pseudophakic cystoid macular edema is otherwise difficult to treat and often left untreated.

Anti-angiogenic properties of rapamycin on human retinal pericytes in an in vitro model of neovascular AMD via inhibition of the mTOR pathway.

PURPOSE: Choroidal neovascularizations (CNV) are partially stabilized through a coverage of pericytes leading to a partial anti-VEGF resistence. Drugs licensed for neovascular AMD (nAMD) do not take this mechanical and growth factor-driven CNV stability into account. The purpose of this work was to see if inhibiting the mammalian target of rapamycin (mTOR) may successfully block angiogenic cellular pathways in primary human retinal pericytes in an in vitro model of nAMD. METHODS: The mTOR inhibitor rapamycin was used to treat human retinal pericytes (HRP) at doses ranging from 0.005 to 15 g/ml. A modified metabolism-based XTT-Assay was used to assess toxicity and anti-proliferative effects. A scratch wound experiment showed the effects on migration. On Cultrex basement membrane gels, the influence of rapamycin on the development of endothelial cell capillary-like structures by human umbilical vein vascular endothelial cells (HUVEC) in the absence and presence of pericytes was investigated. RESULTS: Rapamycin showed no signs of toxicity within its range of solubility. The drug showed dose dependent anti-proliferative activity and inhibited migration into the scratch wound. Endothelial cell tube formation in a HUVEC monoculture was effectively inhibited at 45%. A co-culture of HUVEC with pericytes on Cultrex induced endothelial tube stabilization but was disrupted by the addition of rapamycin leading to degradation of 94% of the tubes. CONCLUSIONS: Rapamycin allows for an efficient modulation of aspects of angiogenesis in pericytes via mTOR-modulation in vitro. Further studies are needed to elucidate whether rapamycin may have an impact on CNV in nAMD in vivo.

Impact of COVID-19 before and after 2020 on Retinal Detachment Management in a Tertiary Eye Hospital in Germany.

INTRODUCTION: COVID-19 has had a tremendous impact on our everyday life. A growing body of evidence indicates that subsequent lockdowns and fear of exposure may have impacted patient care. We analyzed data on incidence and time to surgery in cases of rhegmatogenous retinal detachments (RRD) at three defined time points before, during, and 1 year after the first lockdown period in Germany. METHODS: In this single-center study, we identified all patients who were admitted and treated for a primary RRD in April and May 2020, the time of the first lockdown period in Germany, and compared them with cases of the same time period in the years 2019 and 2021. The time from first occurrence of symptoms to surgery as well as visual outcome was analyzed. RESULTS: A total of 192 patients presented to our tertiary academic referral center with a RRD during the months of April and May in 2019 (72 patients), 2020 (62 patients), and 2021 (58 patients) and were included in this study. There were no significant differences with regard to gender and age. In 2019, the time interval between occurrence and presentation to our hospital amounted to a mean of 5.96 days and in 2021 to mean of 5.45 days. However, in 2020, the time between occurrence and presentation was significantly longer with a mean of 15.36 days. The number of patients presenting with a macula-on retinal detachment was also lowest in 2020 (39.2%) compared to 2019 (50.7%) and 2021 (50.0%). Furthermore, with 1.24 logMAR the mean BCVA upon initial presentation was lower in 2020 compared to 0.93 logMAR in 2019 and 1.06 logMAR in 2021. Six to twelve weeks following surgery, visual acuity had improved in 56.1% of patients in 2019 and 60.0% of patients in 2021 as compared to 59.0% in 2020. CONCLUSION: We found significant differences in terms of elapsed time from first symptoms to surgical management for patients in 2020 in comparison with the same time period in 2019 and 2021. Less strict lockdown policies appear to impact patient behavior and patient care. Further measures, such as questionnaires, might help address which measures may provide safer circumstances for patients to consult health care providers in the case of future strict lockdowns.

Intraocular Pressure after Vitreoretinal Surgery. / Der Intraokulardruck nach Netzhauteingriffen.

Vitreoretinal surgery can lead to elevated intraocular pressure. Causes are multifactorial including both mechanical and pharmacological mechanisms. Therapy initially consists of topical therapy with pressure-lowering eye drops. In case of inadequate response, surgical interventions are indicated.

Enlargement rate of geographic atrophy before and after secondary CNV conversion with associated anti-VEGF treatment.

BACKGROUND: To study the enlargement rate of primary geographic atrophy (GA) before and after diagnosis of a secondary choroidal neovascularization (CNV) treated with anti-vascular endothelial growth factor (VEGF) therapy. METHODS: Five hundred twenty-two consecutive eyes with primary GA were screened for the development of a complicating secondary CNV. Geographic atrophy was measured on blue autofluorescence (BAF) by two readers and calculated into mean growth rate before and after CNV diagnosis. RESULTS: Ten eyes of six patients were included in the study (six study eyes with GA complicated by CNV, four GA only partner eyes). Follow-up was 1.42 ± 0.48 years before and 3.64 ± 2.73 years after CNV. There was no significant difference between mean growth rate before and after CNV (1.58 ± 0.99 vs. 1.39 ± 0.65 mm2/year; p = 0.44) or between study and partner eyes (p = 0.86). Over a mean time of 3.64 ± 2.73 years, a mean of 8.3 ± 2.8 anti-VEGF injections were given. No correlation between the amount of anti-VEGF injections and change in growth rate could be observed (r = 0.58; p = 0.23). CONCLUSION: In this pilot study, primary GA enlargement did not seem to be influenced by a secondary CNV. No association between the intensity of anti-VEGF treatment and changes in atrophy enlargement rates were found. Further studies with larger sample sizes are warranted.

COMPLIANCE AND ADHERENCE OF PATIENTS WITH DIABETIC MACULAR EDEMA TO INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY IN DAILY PRACTICE.

PURPOSE: We assessed differences in compliance and adherence (lateness of patients, visual acuity, reasons for abstaining) between patients with diabetic macular edema (DME) and patients with age-related macular degeneration (AMD), both under anti-vascular endothelial growth factor therapy. METHODS: We included 136 patients with DME (36% women, 65 years, 22 visits, 13.9 injections, and 29.9 months of follow-up) and 109 patients with AMD (59% women, 76 years, 20 visits, 14.7 injections, and 22.3 months of follow-up) (minimum follow-up of 12 months and at least 5 injections). We assessed missed appointments (lateness >14 days) and therapy break-offs (lateness >100 days). All delayed patients were called and interviewed for abstaining reasons. RESULTS: Forty-six percent of patients with DME and 22% of patients with AMD had at least one break-off. Thirty-five percent of patients with DME and 50% of patients with AMD were always on schedule. In patients with DME, there was significant correlation (P = 0.017) between the number of break-offs and change of visual acuity. In 60% DME and 38% AMD of break-off cases, visual acuity was worse than the before break-off. The most common reason for abstaining was comorbidities (33% AMD and 20% DME). CONCLUSION: There are significant differences between patients with AMD and DME regarding compliance and adherence, which also affects outcome. Strategies to tie patients with DME to costly intravitreal therapy need to be developed to improve outcomes and efficacy.

Combined VEGF and PDGF inhibition for neovascular AMD: anti-angiogenic properties of axitinib on human endothelial cells and pericytes in vitro.

PURPOSE: Drugs currently approved for neovascular age-related macular degeneration (nAMD) offer anti-VEGF monotherapy only. Platelet-derived growth factor (PDGF) signaling is pivotal to pericyte-induced stabilization of choroidal neovascularizations (CNV), and causes partial anti-VEGF resistance. No combination therapy for VEGF and PDGF has been approved yet. Axitinib is a tyrosine kinase inhibitor interfering with VEGF and PDGF signaling, and has been approved for the treatment of renal cell carcinoma. This study evaluates anti-angiogenic properties of axitinib in an in-vitro model of choroidal neovascularizations in nAMD. METHODS: Human endothelial cells (HUVEC) and human pericytes (hPC-PL) were treated with axitinib doses ranging from 1.0 ng/ml to 10 µg/ml. Cellular viability and proliferation were assessed with a modified MTT assay. VEGF- and PDGF-stimulated migration was observed in modified Boyden chambers. Formation of capillary structures was evaluated on Cultrex basement membrane. RESULTS: Proliferation was significantly inhibited in both cell lines in a dose-dependent manner. VEGF and PDGF significantly induced, whereas simultaneous axitinib normalized cellular migration in HUVEC and pericytes. On growth-factor-reduced Cultrex, VEGF induced the formation of capillary structures, while axitinib significantly reverted this effect. Axitinib reduced the amount of vessel associated tissue on full growth factor Cultrex. All effects on both cell lines were observed in non-toxic concentrations of axitinib. CONCLUSIONS: Axitinib inhibits angiogenesis in endothelial cells and pericytes via VEGFR and PDGFR modulation in vitro. Further studies are needed to elucidate whether axitinib may also improve therapy of CNV in AMD in vivo by interference with pericyte stabilization of pathological vessels.

Central serous chorioretinopathy.

The pathogenesis of central serous chorioretinopathy (CSC) is still not fully understood. The involvement of corticosteroids is undisputed, although their exact role has not been clarified; other parts of the underlying mechanism of CSC have been mainly elucidated by imaging techniques such as fluorescein and indocyanine green angiography. Even though most cases of CSC are self-limiting, severe as well as recurrent courses exist, and for these patients only a limited number of treatment options are available: laser photocoagulation, with a risk of scotoma and choroidal neovascularization, and photodynamic therapy. In this review article, we give an overview of its epidemiology, the current understanding of its pathogenesis as well as systemic and ocular risk factors. We illuminate modern diagnostic tools as well as current treatment options in the context of CSC, particularly in the light of a better understanding of corticosteroids and their receptors involved in its pathogenesis.

Nonmydriatic ultra-wide-field scanning laser ophthalmoscopy (Optomap) versus two-field fundus photography in diabetic retinopathy.

The purpose of this study was to investigate the diagnostic properties of a 2-laser wavelength nonmydriatic 200° ultra-wide-field scanning laser ophthalmoscope (SLO) versus mydriatic 2-field 45° color fundus photography (EURODIAB standard) for assessing diabetic retinopathy (DR). A total of 143 consecutive eyes of patients with different levels of DR were graded regarding DR level and macular edema based on 2-field color photographs or 1 Optomap Panoramic 200 SLO image. All SLO images were nonmydriatic and all photographs mydriatic. Grading was performed masked to patient and clinical data. Based on photography, 20 eyes had no DR, 44 had mild, 18 moderate and 42 severe nonproliferative DR, and 19 eyes had proliferative DR. Overall correlation for grading DR level compared to Optomap SLO was moderate with kappa 0.54 (p < 0.001), fair-to-moderate in macular edema grading with kappa 0.39 (p < 0.001), and substantial for grading clinically significant macular edema (kappa 0.77). The wide-field SLO offers a wider field of view and can potentially better differentiate lesions by applying the 2 laser wavelengths. However, these advantages over 2-field fundus photography need to be confirmed in further studies.

[Survey on blood thinning therapy in patients with age-related macular degeneration]. / Umfrage zur blutverdünnenden Therapie bei Patienten mit altersabhängiger Makuladegeneration.

BACKGROUND: Patients with age-related macular degeneration (AMD) often receive concomitant systemic blood thinning medications. These are known to increase the risk of severe hemorrhage also in connection with AMD, which can lead to extensive subretinal hemorrhaging. OBJECTIVE: The purpose of this study was to investigate the proportion of patients with AMD and concomitant blood thinning treatment, including the type and reason for blood thinning treatment. METHODS: This survey was prospectively conducted at the University Eye Hospital, Bonn, Germany. Volunteers were recruited during retinal consultations and the consultations for intravitreal injections (IVOM). RESULTS: The questionnaire was completed by 178 patients. The mean age was 81.7 years (58-100) and 101 patients (57.7%) were undergoing blood thinning treatment. The majority of patients were taking antiplatelet agents (n = 59; 58.4%), especially ASA (n = 55; 54.5%). Direct oral anticoagulants (DOAC) were taken by 33 patients (32.7%), including most frequently apixaban (17.8%). Vitamin K antagonists (VKA) was taken by 4 patients (4%). The most common reason for blood thinning treatment was atrial fibrillation (n = 32, 31.7%), followed by stent implantation (n = 20, 19.8%) and stroke (n = 12, 11.9%) but 13 patients (12.9%) did not know why they were undergoing blood thinning treatment. No clear indications for the use of blood thinners were found in 31 patients (30.7%). CONCLUSION: A large proportion of patients with AMD undergo blood thinning treatment; however, not every patient has a clear indication. Due to the increased risk of bleeding, the use of blood thinners should be critically evaluated in close cooperation with primary care physicians and cardiologists.

Tumor Control Probability and Time-Dose-Response Modeling for Stereotactic Radiosurgery of Uveal Melanoma.

PURPOSE: Uveal melanoma (UM), although a rare malignancy, stands as the most prevalent intraocular malignancy in adults. Controversies persist regarding the dose dependency of local control (LC) through radiation therapy. This study sought to elucidate the significance of the prescription dose by employing time-dose-response models for patients with UM receiving photon-based stereotactic radiosurgery (SRS). METHODS AND MATERIALS: The analysis included patients with UM treated between 2005 and 2019. All patients underwent single-fraction SRS. Datapoints were separated into 3 dose groups, with Kaplan-Meier analysis performed on each group, from which time-dose-response models for LC were created at 2, 4, and 7 years after SRS using maximum-likelihood fitted logistic models. RESULTS: Outcomes from 594 patients with 594 UMs were used to create time-dose-response models. The prescribed doses and the number of patients were as follows: 17 to 19 Gy (24 patients), 20 Gy (122 patients), 21 Gy (442 patients), and 22 Gy (6 patients). Averaged over all patients and doses, LC rates at 2, 4, and 7 years were 94.4%, 88.2%, and 69.0%, respectively. Time-dose-response models for LC demonstrated a dose-dependent effect, showing 2-year LC rates of more than 90% with 20 Gy and 95% with 22 Gy. For 4 years and a LC of 90%, a dose of approximately 21 Gy was required. After 7 years, the 21 Gy prescription dose was predicted to maintain a LC above 70%, sharply declining to less than 60% LC with 19 Gy and less than 40% with 18 Gy. CONCLUSIONS: In contrast to prior findings, the time-dose-response models for UM undergoing photon-based SRS emphasize the critical role of the prescription dose in achieving lasting LC. The dose selection must be carefully balanced against toxicity risks, considering tumor geometry and individual patient characteristics to tailor treatments accordingly.

Impact of lens autofluorescence and opacification on retinal imaging.

BACKGROUND: Retinal imaging, including fundus autofluorescence (FAF), strongly depends on the clearness of the optical media. Lens status is crucial since the ageing lens has both light-blocking and autofluorescence (AF) properties that distort image analysis. Here, we report both lens opacification and AF metrics and the effect on automated image quality assessment. METHODS: 227 subjects (range: 19-89 years old) received quantitative AF of the lens (LQAF), Scheimpflug, anterior chamber optical coherence tomography as well as blue/green FAF (BAF/GAF), and infrared (IR) imaging. LQAF values, the Pentacam Nucleus Staging score and the relative lens reflectivity were extracted to estimate lens opacification. Mean opinion scores of FAF and IR image quality were compiled by medical readers. A regression model for predicting image quality was developed using a convolutional neural network (CNN). Correlation analysis was conducted to assess the association of lens scores, with retinal image quality derived from human or CNN annotations. RESULTS: Retinal image quality was generally high across all imaging modalities (IR (8.25±1.99) >GAF >BAF (6.6±3.13)). CNN image quality prediction was excellent (average mean absolute error (MAE) 0.9). Predictions were comparable to human grading. Overall, LQAF showed the highest correlation with image quality grading criteria for all imaging modalities (eg, Pearson correlation±CI -0.35 (-0.50 to 0.18) for BAF/LQAF). BAF image quality was most vulnerable to an increase in lenticular metrics, while IR (-0.19 (-0.38 to 0.01)) demonstrated the highest resilience. CONCLUSION: The use of CNN-based retinal image quality assessment achieved excellent results. The study highlights the vulnerability of BAF to lenticular remodelling. These results can aid in the development of cut-off values for clinical studies, ensuring reliable data collection for the monitoring of retinal diseases.

Personalized Lens Correction Improves Quantitative Fundus Autofluorescence Analysis.

Purpose: Quantitative fundus autofluorescence (QAF) currently deploys an age-based score to correct for lens opacification. However, in elderly people, lens opacification varies strongly between individuals of similar age, and innate lens autofluorescence is not included in the current correction formula. Our goal was to develop and compare an individualized formula. Methods: One hundred thirty participants were examined cross-sectionally, and a subset of 30 participants received additional multimodal imaging 2-week post-cataract-surgery. Imaging included the Scheimpflug principle, anterior chamber optical coherence tomography (AC-OCT), lens quantitative autofluorescence (LQAF), and retinal QAF imaging. Among the subset, least absolute shrinkage and selection operator regression and backward selection was implemented to determine which lens score best predicts the QAF value after lens extraction. Subsequently, a spline mixed model was applied to the whole cohort to quantify the influence of LQAF and Scheimpflug on QAF. Results: Age and LQAF measurements were found to be the most relevant variables, whereas AC-OCT measurements and Scheimpflug were eliminated by backward selection. Both an increase in Scheimpflug and LQAF values were associated with a decrease in QAF. The prediction error of the spline model (mean absolute error [MAE] ± standard deviation) of 32.2 ± 23.4 (QAF a.u.) was markedly lower compared to the current age-based formula MAE of 96.1 ± 93.5. Both smooth terms, LQAF (P < 0.01) and Scheimpflug (P < 0.001), were significant for the spline mixed model. Conclusions: LQAF imaging proved to be the most predictive for the impact of the natural lens on QAF imaging. The application of lens scores in the clinic could improve the accuracy of QAF imaging interpretation and might allow including aged patients in future QAF studies.

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.

The Treatment Patterns with Brolucizumab in Germany (REALIZE) Study: A Retrospective Cohort Study Based on Longitudinal Prescription Data.

INTRODUCTION: This study describes real-world treatment patterns in Germany for brolucizumab, an anti-vascular endothelial growth factor (anti-VEGF) therapy for neovascular age-related macular degeneration (nAMD). METHODS: This single-arm retrospective cohort study used German patient-level prescription data. Patients aged ≥ 50 years, who received ≥ 1 brolucizumab prescription in one eye only (unilateral) and had a minimum of 12 months follow-up were included. Three cohorts were defined from the overall population: anti-VEGF treatment-naive patients ("treatment-naive"); anti-VEGF treatment-experienced patients ("treatment-experienced"); and of the treatment-experienced cohort, patients persistent on brolucizumab for 12 months ("treatment-experienced persistent"), i.e. who received ≥ 2 brolucizumab injections and did not discontinue or use other anti-VEGF agents in that period. Descriptive statistics were used to analyse patient characteristics and injection intervals. RESULTS: A total of 2089 patients with at least 12 months follow-up and one brolucizumab injection were analysed. Most were female (58.1%), aged 80+ years (54.7%). A total of 539 (25.8%) were treatment-naive, 1550 (74.2%) treatment-experienced and, of those, 787 (50.8%) were persistent. Overall, the median (interquartile range, IQR) number of brolucizumab injections during the 12 months follow-up was 5.0 (3.0-8.0). In the treatment-naive and treatment-experienced sub-cohorts it was 5.0 (3.0-8.0) and 5.0 (3.0-9.0) injections, respectively. In the treatment-experienced persistent cohort the median (IQR) number of injections was 8.0 (5.0-10.0). In this same cohort, the median (IQR) treatment interval between anti-VEGF injections before switch to brolucizumab was 5.1 (4.0-8.0) weeks, whilst the brolucizumab interval at 12 months after switch was 8.0 (6.0-11.9) weeks. Of treatment-experienced patients, 67% extended their treatment interval and those with pre-switch intervals less than 6 weeks (< q6w), in particular, had meaningful treatment interval extensions. CONCLUSION: Patients who switched to brolucizumab had a median treatment interval extension of about 3 weeks at 12 months. These results show that treatment with brolucizumab has the potential to reduce treatment burden in patients with nAMD in routine clinical practice.

Influence of a Prostaglandin F2α Analogue on Corneal Hysteresis and Expression of Extracellular Matrix Metalloproteinases 3 and 9.

Purpose: Low corneal hysteresis (CH) is associated with an increased risk of glaucoma. Prostaglandin analogue (PGA) eye drops may exert their intraocular pressure (IOP)-lowering effect partially by increasing CH. Methods: Twelve pairs of organ-cultured human donor corneas were used in an ex vivo model. In each case, one cornea was treated with PGA (Travoprost) for 30 days, whereas the other served as an untreated control. IOP levels were simulated in an artificial anterior chamber model. CH was measured using the Ocular Response Analyzer (ORA). Corneal expression of matrix-metalloproteinases (MMPs) was assessed by immunhistochemistry and real-time polymerase chain reaction (RT-PCR). Results: Increased CH was observed in the PGA-treated corneas. However, at IOP between 10 and 20 mm Hg, CH was increased in PGA-treated corneas (13.12 ± 0.63 mm Hg; control: 12.34 ± 0.49 mm Hg), although not significantly (P = 0.14). CH was significantly increased at higher IOP levels (21-40 mm Hg; PGA-treated: 17.62 ± 0.40 mm Hg; control: 11.60 ± 0.39, P < 0.0001). Treatment with PGA resulted in increased expression of MMP-3 and MMP-9. Conclusions: CH was increased after exposure to PGA. However, this increase was significant only in eyes with higher IOP (>21 mm Hg). A significant increase in MMP-3 and -9 was observed in PGA-treated corneas, indicating structural changes in corneal biomechanics caused by PGA. Translational Relevance: PGAs alter biomechanical structures by directly upregulating MMP-3 and -9, and the increase in CH is dependent on the level of IOP. Therefore, PGAs may have a greater effect when baseline IOP is higher.