Geographic Atrophy in AMD: Prognostic Factors Based on Long-Term Follow-Up.

INTRODUCTION: The aim of this large-scale long-term retrospective study was to show the enlargement rate (ER) of geographic atrophy (GA) in age-related macular degeneration (AMD), defined as complete retinal pigment epithelium and outer retinal atrophy (cRORA), to find predictors of progression in a clinical routine setting and to compare GA evaluation methods. METHODS: All patients available in our database with follow-up of at least 24 months and cRORA in at least one eye, regardless of neovascular AMD being present, were included. SD-OCT and fundus autofluorescence (FAF) evaluations were performed according to a standardized protocol. The cRORA area ER, the cRORA square root area ER, the FAF GA area, and the condition of the outer retina (inner-/outer-segment [IS/OS] line and external limiting membrane [ELM] disruption scores) were determined. RESULTS: 204 eyes of 129 patients were included. Mean follow-up time was 4.2 ± 2.2 (range 2-10) years. 109 of 204 (53.4%) eyes were classified as MNV-associated GA in AMD (initially or during follow-up); 95 of 204 (46.6%) eyes were classified as pure GA in AMD. The primary lesion was unifocal in 146 (72%) eyes and multifocal in 58 (28%) eyes. A strong correlation was observed between the area of cRORA (SD-OCT) and the FAF GA area (r = 0.924; p < 0.001). Mean ER was 1.44 ± 1.2 mm2/year, mean square root ER 0.29 ± 0.19 mm/year. There was no significant difference in mean ER between eyes without (pure GA) and with intravitreal anti-VEGF injections (MNV-associated GA) (0.30 ± 0.19 mm/year vs. 0.28 ± 0.20 mm/year; p = 0.466). Eyes with multifocal atrophy pattern at baseline had a significantly higher mean ER compared to eyes with unifocal pattern (0.34 ± 0.19 mm/year vs. 0.27 ± 1.19 mm/year; p = 0.008). There were moderate significant correlations between ELM and IS/OS disruption scores and visual acuity at baseline, 5 and 7 years (all r values ca. -0.5; p < 0.001). In multivariate regression analysis, a multifocal cRORA pattern at baseline (p = 0.022) and a smaller baseline lesion size (p = 0.036) were associated with a higher mean ER. CONCLUSION: SD-OCT-evaluated cRORA area might serve as a GA parameter comparable to traditional FAF measurement in clinical routine. The dispersion pattern and baseline lesion size might be predictors of ER, whereas anti-VEGF treatment seems not to be associated with ER.

Predictors for 2-Year Functional and Morphological Outcomes of a Treat-and-Extend Regimen with Ranibizumab in Patients with Diabetic Macular Edema.

PURPOSE: The purpose of the study was to investigate longer term functional and morphological outcomes and their predictors in diabetic macular edema (DME) following a treat-and-extend regimen (TER) without loading dose under ranibizumab. METHODS: Patient data were reviewed and analyzed retrospectively over a period of 24 months after initiation of TER. Best-corrected visual acuity (BCVA), treatment frequency, and quantitative and qualitative spectral-domain optical coherence tomography parameters were assessed. RESULTS: 118 eyes of 87 patients were included. A mean of 9.74 ± 2.13 injections in the first and 7.63 ± 2.29 in the second year were applied. There were significant gains of BCVA and reductions in central retinal thickness from baseline to 12 and 24 months (all p < 0.001). Percentage of eyes with an intact inner segment/outer segment (IS/OS) junction increased from 15.3% at baseline to 42.1% at 24 months (p < 0.001). An intact IS/OS junction at baseline increased the probability of having a dry retina after 12 months by 79.3% (p = 0.017) and after 24 months by 88.1% (p = 0.040). Less IS/OS disruption at baseline predicted longer maximum recurrence-free treatment intervals at 2 years (r = -0.345, p < 0.001) and better BCVA at 1 year (r = -0.347, p < 0.001). Baseline bigger intraretinal cysts were associated with more IS/OS disruption at 24 months (r = 0.305, p = 0.007). Younger age and lower BCVA at baseline were predictive for a higher BCVA gain at 24 months (p = 0.046, p < 0.001). CONCLUSION: Ranibizumab applied in a TER without loading dose in DME significantly improves visual acuity and retinal anatomical structure throughout 2 years. The evaluated predictors might help guide routine clinical treatment in DME.

Contrast sensitivity and binocular reading speed best correlating with near distance vision-related quality of life in bilateral nAMD.

PURPOSE: Bilateral neovascular age-related macular degeneration (nAMD) causes difficulties in daily life, especially with regard to near-vision tasks, despite well preserved Early Treatment of Diabetic Retinopathy Study (ETDRS) best corrected visual acuity (BCVA) at distance. Therefore, alternative visual function measures were evaluated in terms of their correlation with vision-related quality of life scores (QoL). METHODS: A prospective cross-sectional pilot study including patients with a diagnosis of bilateral nAMD having lesions within the central 1 mm ETDRS grid subfield. Standardised testing included a vision-related QoL assessment (NEI-VFQ25), best corrected visual acuity (BCVA), low luminance visual acuity (LLVA), Radner maximum reading speed and Pelli-Robson contrast sensitivity (CS). RESULTS: N = 54. The mean better eye (range) BCVA was 79 (55-96) letters, median (range) LLVA 79.5 (58-97) letters and median (range) CS 1.35 (0-1.65) log units. Mean binocular maximum reading speed was 117.33 ± 28.42 wpm. The best correlations with the near subscale score were found for CS followed by binocular maximum reading speed (r = 0.59, p = 0.0001; r = 0.36, p = 0.008, respectively). A weaker correlation was observed for the BCVA in the better eye (r = 0.33, p = 0.02). The correlation between the NEI-VFQ25 distance subscale and BCVA was weaker (r = 0.37, p = 0.005) than the correlations with CS (r = 0.67, p = 0.0001) and LLVA (r = 0.40, p = 0.003). CONCLUSIONS: For patients with a bilateral centre-involving nAMD, the best correlation with near QoL was the better eye CS followed by maximum binocular reading speed. These measures could be valuable in quantifying vision-related QoL outcomes in AMD clinical trials.

Outcome Predictors of SD-OCT-Driven Intravitreal Ranibizumab in Choroidal Neovascularization due to Myopia.

PURPOSE: To analyze the efficacy and outcome predictors of SD-OCT (spectral-domain optical coherence tomography)-driven ranibizumab treatment in patients with choroidal neovascularization due to myopia (mCNV). METHODS: This prospective investigator-initiated study includes 20 patients with treatment-naïve mCNV. Evaluation included best-corrected visual acuity (BCVA), morphological SD-OCT parameters, and treatment frequency. RESULTS: From baseline to month 12, BCVA improved from 58.5 ± 16.9 to 66.1 ± 14.9 letters. Central retinal thickness (CRT) significantly decreased, and qualitative SD-OCT parameters improved. Better baseline visual acuity (VA), lower spherical equivalent, better inner/outer segment line and external limiting membrane integrity showed a significant positive effect on BCVA outcome. Less fluctuation in CRT (worst minus best CRT) indicated better BCVA at 12 months. No serious adverse events occurred. CONCLUSIONS: SD-OCT-guided intravitreal ranibizumab treatment in mCNV was efficient and safe. We determined useful predictive factors in regard to VA outcome after 12 months.

Repeated Dexamethasone Intravitreal Implant for the Treatment of Diabetic Macular Oedema Unresponsive to Anti-VEGF Therapy: Outcome and Predictive SD-OCT Features.

PURPOSE: To investigate dexamethasone intravitreal implant 0.7 mg (DEX implant) for the treatment of diabetic macular oedema (DME) refractory to anti-vascular endothelial growth factor (anti-VEGF) therapy and evaluate predictive factors. METHODS: Two-centre retrospective interventional case series, including 40 eyes of 31 patients treated with DEX implant for at least 2 consecutive cycles. RESULTS: Mean ± SD intervals from implantation to recurrence in the first (4.2 ± 1.0 months) and second cycles (4.0 ± 0.9 months) were not significantly different. Best corrected visual acuity improved significantly (p < 0.001) by 7.0 ± 8.4 letters from baseline to month 2, and by 5.1 ± 6.9 letters between the first and second cycles. Central retinal thickness reduction 2 months after implantation was greater after the first (-194 ± 172 µm) than the second cycle (-134 ± 150 µm). Ellipsoid zone-external limiting membrane (EZ-ELM) disruption score decreased from 1.39 ± 1.16 at baseline to 1.24 ± 1.16 (p = 0.0832) after cycle 1 and remained stable 2 months after cycle 2. Eyes with persisting severe EZ-ELM disruption (score >2, n = 10) 2 months after the first DEX implant showed significantly (p = 0.0153) smaller visual acuity (VA) gains than eyes with less severe (score ≤2) EZ-ELM disruption. CONCLUSION: Repeated intravitreal DEX injections with average intervals of 4 months are valuable in patients with DME refractory to anti-VEGF therapy. Disorganization of outer retinal layers (EZ-ELM) may predict smaller VA gains if evaluated after initial reduction of macular oedema.

Spectral-Domain Optical Coherence Tomography-Driven Treat-and-Extend and Pro Re Nata Regimen in Patients with Macular Oedema due to Retinal Vein Occlusion: 24-Month Evaluation and Outcome Predictors.

PURPOSE: To analyse the efficacy and outcome predictors of ranibizumab using a spectral-domain optical coherence tomography (SD-OCT)-driven treat-and-extend regimen (TER) versus SD-OCT-driven pro re nata regimen (PRN) in patients with cystoid macular oedema (CME) due to branch or central retinal vein occlusion (BRVO, CRVO). METHODS: Retrospective, consecutive case series. Evaluation included best corrected visual acuity (BCVA), morphological parameters on SD-OCT, and treatment frequency. RESULTS: From baseline to months 12, 18, and 24, BCVA improved by 16.6 ± 13.1, 15.5 ± 14.4, and 16.6 ± 15.8 letters, respectively, in TER (n = 45), compared to 11.3 ± 17.0, 11.0 ± 15.0, and 10 ± 20.5 letters in PRN (n = 31) (p = 0.152, p = 0.237, p = 0.172). The mean reduction in central retinal thickness was -261 ± 189, -272 ± 188, and -264 ± 158 µm, respectively, in TER, compared to -130 ± 196, -140 ± 210, and -166 ± 207 µm in PRN (p = 0.006, p = 0.017, p = 0.064). 59% (53%) of TER and 22% (17%) of PRN patients showed no intra- or subretinal fluid on SD-OCT at 12 (24) months. Using TER, the maximum recurrence-free treatment interval increased from 8.9 ± 2.3 weeks at 12 months to 9.8 ± 2.3 and 10.5 ± 2.7 weeks at 18 and 24 months, respectively. The number of injections was significantly higher in the TER than in the PRN group. CONCLUSIONS: In CME, due to BRVO/CRVO, TER provides better morphological outcome using more injections than PRN.

INTRAVITREAL AFLIBERCEPT IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION WITH LIMITED RESPONSE TO RANIBIZUMAB: A Treat-and-Extend Trial.

PURPOSE: To evaluate aflibercept treat-and-extend regimen for treatment of neovascular age-related macular degeneration in patients with limited response to ranibizumab. METHODS: This prospective single-arm trial included 33 patients with neovascular age-related macular degeneration pretreated with treat-and-extend regimen ranibizumab for ≥6 months who failed to be extended to a 6-week interval at least twice. All patients received aflibercept (2 mg/0.05 mL) at baseline, and were subsequently treated according to treat-and-extend regimen, starting with a 4-week interval and extending in 2-week steps. Evaluations included mean maximum recurrence-free treatment interval; best-corrected visual acuity; central retinal thickness; and pigment epithelium detachment height and horizontal diameter. RESULTS: At Week 24, the maximum recurrence-free treatment interval increased to ≥6 weeks in ∼35% of patients, whereas the mean interval was 4.9 ± 1.3 weeks. Best-corrected visual acuity score remained stable, but significant reductions in central retinal thickness (P < 0.001) and pigment epithelium detachment height (P = 0.001) were observed compared with baseline, as was a small decrease in horizontal pigment epithelium detachment diameter (P = 0.035). CONCLUSION: After switching patients with limited ranibizumab response to aflibercept, signs of choroidal neovascularization activity regressed, and an increased duration of treatment effects was seen in approximately one-third of lesions, but visual acuity was unchanged.

Baseline Optical Coherence Tomography Findings as Outcome Predictors after Switching from Ranibizumab to Aflibercept in Neovascular Age-Related Macular Degeneration following a Treat-and-Extend Regimen.

PURPOSE: To evaluate outcome predictors of aflibercept in neovascular age-related macular degeneration pretreated with ranibizumab based on a treat-and-extend regimen (TER). METHODS: We performed a retrospective evaluation of 18-month follow-up of 45 consecutive patients with limited response to ranibizumab. RESULTS: At month 18, mean central retinal thickness and intraretinal fluid (IRF) height were significantly reduced. The recurrence-free treatment interval (RFTI) increased from 7.0 ± 1.8 to 8.5 ± 2.4 weeks (p = 0.01); visual acuity remained stable. At month 18, 58.1% of patients showed a longer RFTI. At month 12, eyes with baseline subretinal fluid (SRF) had a shorter RFTI than those without SRF (p = 0.032). Eyes with baseline IRF showed a longer RFTI than those without IRF (p = 0.037). Baseline hyperreflective foci (HRF) presence indicated improvement in SRF (p = 0.024) and IRF at month 12 (p = 0.049). CONCLUSION: Baseline HRF presence predicted better morphological outcome, while SRF predicted a shorter RFTI and IRF a longer RFTI after switching from ranibizumab to aflibercept within a TER.

[Retinal vein occlusion: an interdisciplinary approach]. / Retinale Venenverschlüsse - ein interdisziplinäres Problem.

Retinal vein occlusion provide a common cause of significant visual reduction but also late ocular complications. The medical care of these patients pursue two goals: On the one hand vision threatening complications need to be identified and treated, and on the other hand treatable risk factors are need to be identified and treated. This paper summarizes the common ophthalmological therapeutic approaches as well as recommended medical evaluations carried out by the general practitioner. This supports the interdisciplinary approach in evaluating and treating retinal vein occlusions by ophthalmologists and the general practitioners/specialist in internal medicine.

Ranibizumab plus verteporfin photodynamic therapy in neovascular age-related macular degeneration: 12 months of retreatment and vision outcomes from a randomized study.

PURPOSE: To investigate the injection frequency and visual acuity (VA) outcomes with combination therapy (ranibizumab plus verteporfin photodynamic therapy, PDT) versus monotherapy (ranibizumab). METHODS: A total of 40 patients with exudative age-related macular degeneration were randomized 1:1 to ranibizumab 0.3 mg plus single standard verteporfin PDT or ranibizumab 0.3 mg plus sham PDT. Ranibizumab was administered 3 times monthly followed by 'as needed' to month 12 based on predetermined vision/anatomical criteria. Retreatment rates, VA outcomes and safety were assessed. RESULTS: During months 3-12, combination therapy patients required fewer ranibizumab injections (mean 1.3) compared with monotherapy patients (2.8). Mean VA improved by 9.0 letters with combination therapy versus 7.5 letters in the monotherapy group at month 12. Both treatment regimens were well tolerated. CONCLUSION: The need for ranibizumab retreatment might be reduced by administering a single verteporfin PDT on the same day as the first ranibizumab injection, without compromising VA outcomes or safety.

Prospective Study Comparing Quantitative Self-Monitoring Metamorphopsia Measurement Tools in Myopic Choroidal Neovascularization (mCNV).

Purpose: To assess the ability of two self-monitoring digital devices to detect metamorphopsia in myopic choroidal neovascularization (mCNV) and compare their usability. Patients and Methods: This was a 12-month prospective observational study at a tertiary care eye hospital, Switzerland. Twenty-three Caucasian patients with mCNV were recruited, 21 eyes were analyzed. Primary and secondary outcome measures: Primary outcome measures were the metamorphopsia index scores as assessed by the two self-monitoring digital devices (Alleye App and AMD - A-Metamorphopsia-Detector software) at baseline, at 6 and 12 months and individual optional visits in between. Secondary outcome measures included best corrected visual acuity and morphological parameters (including disease activity) as evaluated by spectral-domain optical coherence tomography and fundus autofluorescence imaging. Location of mCNV was graded using the Early Treatment of Diabetic Retinopathy Study grid overlay. A usability questionnaire was administered at 12 months. Bland-Altman plots evaluated the limits of agreement of both devices. Linear regression analysis assessed the correlation between the difference and the average of the two scores. Results: A total of 202 tests were performed. Disease activity of mCNV was observed at least once in 14 eyes. Both scores concordantly detected metamorphopsia exhibiting a displaced scale of measurement yielding a coefficient of determination of 0.99. Concordance rate for pathological scores was 73.3%. Both scores were not significantly different in active and inactive mCNV. Overall, the usability scores were higher for the Alleye App than the AMD - A-Metamorphopsia-Detector software (4.61±0.56 vs 3.31±1.20; p<0.001). In subjects aged >75 years, scores were slightly lower (4.08±0.86 vs 2.97±1.16; p= 0.032). Conclusion: Whilst both self-monitoring devices concordantly identified metamorphopsia, they might act as an adjunct to hospital visits, but due to slight reactivations in mCNV and presence of metamorphopsia also in inactive disease the ability of detecting early mCNV activity might be limited.

A systematic evaluation of human expert agreement on optical coherence tomography biomarkers using multiple devices.

OBJECTIVES: To assess the agreement in evaluating optical coherence tomography (OCT) variables in the leading macular diseases such as neovascular age-related macular degeneration (nAMD), diabetic macular oedema (DMO) and retinal vein occlusion (RVO) among OCT-certified graders. METHODS: SD-OCT volume scans of 356 eyes were graded by seven graders. The grading included presence of intra- and subretinal fluid (IRF, SRF), pigment epithelial detachment (PED), epiretinal membrane (ERM), conditions of the vitreomacular interface (VMI), central retinal thickness (CRT) at the foveal centre-point (CP) and central millimetre (CMM), as well as height and location of IRF/SRF/PED. Kappa statistics (κ) and intraclass correlation coefficient (ICC) were used to report categorical grading and measurement agreement. RESULTS: The overall agreement on the presence of IRF/SRF/PED was κ = 0.82/0.85/0.81; κ of VMI condition was 0.77, that of ERM presence 0.37. ICC for CRT measurements at CP and CMM was excellent with an ICC of 1.00. Height measurements of IRF/SRF/PED showed robust consistency with ICC = 0.85-0.93. There was substantial to almost perfect agreement in locating IRF/SRF/PED with κ = 0.67-0.86. Between diseases, κ of IRF/SRF presence was 0.69/0.80 for nAMD, 0.64/0.83 for DMO and 0.86/0.89 for RVO. CONCLUSION: Even in the optimized setting, featuring certified graders, standardized image acquisition and the use of a professional reading platform, there is a disease dependent variability in biomarker evaluation that is most pronounced for IRF in nAMD as well as DMO. Our findings highlight the variability in the performance of human expert OCT grading and the need for AI-based automated feature analyses.

Brolucizumab in Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema: Ophthalmology and Diabetology Treatment Aspects.

Anti-vascular endothelial growth factor (anti-VEGF) therapies have become the standard of care in the treatment of neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME), resulting in a remarkable decrease in disease-related vision loss. However, the need for regular injections places a significant burden on patients, caregivers, and the healthcare system and improvements in vision may not be maintained long term. As a result of its drying potency and duration of action, brolucizumab, an intravitreal anti-VEGF therapy approved for the treatment of nAMD and DME, could decrease injection frequency for patients and provide an efficacious treatment; however, balancing its benefits and risks can be challenging. There have been reports of intraocular inflammation (IOI) in patients treated with brolucizumab, which, if left untreated, may result in severe vision loss. Recent evidence, however, indicates that early recognition of IOI and prompt and aggressive systemic corticosteroid treatment in response to posterior segment involvement can lead to favorable outcomes in these relatively rare but severe cases. A series of consensus meetings were conducted in 2022 between Swiss medical retina experts and diabetologists, discussing the current data for brolucizumab and exploring various challenges to its use, including the associated risk of IOI. The outcome is a collation of practical insights and guidance for ophthalmologists on the use of brolucizumab in patients with nAMD and DME, including patient selection and assessment, treatment regimen and monitoring, and the recognition and management of adverse events.

Transforming ophthalmology in the digital century-new care models with added value for patients.

Ophthalmology faces many challenges in providing effective and meaningful eye care to an ever-increasing group of people. Even health systems that have so far been able to cope with the quantitative patient increase, due to their funding and the availability of highly qualified professionals, and improvements in practice routine efficiency, will be pushed to their limits. Further pressure on care will also be caused by new active substances for the largest group of patients with AMD, the so-called dry form. Treatment availability for this so far untreated group will increase the volume of patients 2-3 times. Without the adaptation of the care structures, this quantitative and qualitative expansion in therapy will inevitably lead to an undersupply.There is increasing scientific evidence that significant efficiency gains in the care of chronic diseases can be achieved through better networking of stakeholders in the healthcare system and greater patient involvement. Digitalization can make an important contribution here. Many technological solutions have been developed in recent years and the time is now ready to exploit this potential. The exceptional setting during the SARS-CoV-2 pandemic has shown many that new technology is available safely, quickly, and effectively. The emergency has catalyzed innovation processes and shown for post-pandemic time after that we are equipped to tackle the challenges in ophthalmic healthcare - ultimately for the benefit of patients and society.

Peripapillary and macular microvasculature in neovascular age-related macular degeneration in long-term and recently started anti-VEGF therapy versus healthy controls.

Aim: To investigate the peripapillary and macular microvasculature in neovascular age-related macular degeneration (nAMD) in recently started versus long-term anti-vascular endothelial growth factor (VEGF) therapy and healthy controls. Methods: Eyes with nAMD treated in a treat-and-extend regimen were assigned to group 1 (<5 injections) or 2 (≥20 injections) whereas group 3 constituted the healthy age-matched controls. Blood flow signals were acquired using PLEX® Elite 9000 swept-source optical coherence tomography angiography (OCTA) of the macular and peripapillary regions. Mean ganglion cell complex (GCC) thickness values were quantified using spectral-domain optical coherence tomography (SD-OCT). Results: Including 80 eyes whereof 40 controls, macular superficial perfusion density was significantly reduced in group 1 and 2 compared to controls (p < 0.001; p = 0.010) without a difference between groups 1 and 2. Peripapillary perfusion parameters did not correlate with post-operative intraocular pressure (IOP) or number of anti-VEGF injections. Mean peripapillary flux index was significantly lower in group 2 than in controls (p = 0.023) and significantly decreased in the nasal quadrants for both AMD groups compared to group 3 (p = 0.013; p < 0.001). Mean peripapillary perfusion density was significantly reduced in both AMD groups compared to controls (0.515 ± 0.02 versus 0.556 ± 0.03, p < 0.0001). Conclusion: Frequency of anti-VEGF treatment in nAMD and post-operative IOP showed no correlation with peripapillary perfusion parameters, but anti-VEGF treated nAMD patients exhibited partly altered peripapillary perfusion compared to healthy controls. Reduced macular perfusion density of the inner retina in anti-VEGF treated nAMD compared to healthy controls might be discussed as an anti-VEGF treatment effect or a characteristic of nAMD.

Microvascular abnormalities and long-term efficacy after stereotactic radiotherapy under continued intravitreal anti-VEGF treatment for neovascular AMD.

BACKGROUND: For treatment of neovascular age-related macular degeneration (nAMD), multiple intravitreal injections of drugs targeting vascular endothelial growth factors (VEGF) result in a high burden for patients and healthcare systems. Low-energy stereotactic radiotherapy (SRT) might reduce the anti-VEGF need. This study evaluated the long-term efficacy and safety of adjunct SRT to anti-VEGF injections in a treat-and-extend regimen in nAMD. METHODS: 50 consecutive patients were followed 3 years after single-session SRT, a safety analysis including standardised study imaging, and a reading centre based image analysis was performed after 2 years. RESULTS: After increase from baseline (4.24±0.66 weeks) to 12 months (7.52±3.05 weeks, p<0.001), mean recurrence-free anti-VEGF treatment interval remained stable at 24 (7.40±3.17, p=0.746) and 36 months (6.89±3.00, p=0.175). Mean visual acuity change was -5.8±15.9 and -11.0±20.1 letters at 24 and 36 months, respectively. 36% of eyes showed microvascular abnormalities (MVAs) on colour fundus photography and/or fluoresceine angiography most frequently located in parafoveal inferior and nasal regions. CONCLUSION: In real life, low-energy SRT was associated with a reduced anti-VEGF injection frequency through year 3. However, due to an observed visual acuity reduction and remarkable number of MVAs, a close follow-up of these patients is recommended. The real-life use, optimal treatment schedule and dose should be rediscussed critically.

External Limiting Membrane Disruption Predicts Long-Term Outcome in Strict Treat-And-Extend Regimen in Neovascular Age-Related Macular Degeneration.

The use of anti-vascular-endothelial growth factor agents for neovascular age-related macular degeneration (nAMD) in different treatment schemes is widely common in clinical practice. However, there is currently limited data on the long-term outcomes of a strict treat-and-extend regimen (TER) and imaging biomarkers to predict both functional outcome and the potential for a TER exit due to success. In this retrospective study we followed treatment-naïve subjects with nAMD starting treatment with either ranibizumab or aflibercept in a TER without loading dose but with predefined exit criteria for up to 8 years. We evaluated both the functional outcome and several spectral-domain optical coherence tomography parameters in a follow-up mode using a standardized protocol. Within the 211 eyes followed for a mean of 60.3 ± 20.9 months, follow-up adherence was high with major part of discontinuations of TER being due to success. Mean best-corrected visual acuity (BCVA) increased from initially 63.9 ± 15.5 ETDRS letters to 70.0 ± 14.7 after 1 year (+6.1 letters, p < 0.001) and to 68.5 ± 18.1 (+4.6 letters, p = 0.028) at 5 years. A worse BCVA (p = 0.001) and a better external limiting membrane (ELM) disruption score at baseline predicted (p = 0.019) BCVA gain at 5 years. The probability of reaching the exit criteria was significantly associated with a better ELM disruption score (p = 0.044) and the absence of a central pigment epithelial detachment (PED) (p = 0.05) at baseline. Significant visual gains were sustained in a long-term TER in a real-world setting. Integrity of ELM at baseline predicted BCVA gain at 5 years and the potential for TER exit due to success.

Polypoidal Choroidal Vasculopathy after Stereotactic Radiotherapy for Neovascular Age-Related Macular Degeneration: A Case Report with Long-Term Follow-Up.

Several adjunct therapies to the gold standard anti-vascular endothelial growth factor (anti-VEGF) intravitreal injections have been discussed for the treatment of neovascular age-related macular degeneration (nAMD). Low-dose stereotactic radiotherapy (SRT) showed the potential to lower the treatment burden by reducing the anti-VEGF treatment frequency at least over 2-3 years but was associated with retinal microvascular abnormalities in a few cases. We report a 6-year follow-up of a case with bilateral nAMD under anti-VEGF treatment which developed multiple polypoid choroidal vasculopathy (PCV) lesions in the eye adjunct treated with low-dose SRT. The fellow eye suffering from nAMD for the same period of time but never been treated with SRT did not show PCV during the long-term follow-up. We hope to increase the awareness of possible choroidal changes such as PCV in similar patients by sharing this report.

High frequency SD-OCT follow-up leading to up to biweekly intravitreal ranibizumab treatment in neovascular age-related macular degeneration.

A remarkable proportion of neovascular age-related macular degeneration (nAMD) patients respond rather poorly to ranibizumab treatment, in spite of the minimum 4-week follow-up and treatment interval. Usually, retreatments are based on nAMD activity as evaluated by Spectral-domain Optical coherence Tomography (SD-OCT), biomicroscopic fundus examination and visual acuity changes. In this prospective pilot study, we aimed to study SD-OCT changes in a high-frequent follow-up manner (weekly (month 0-6), biweekly (month 7-12)) throughout the first year, which consequently led to intravitreal ranibizumab being administered up to biweekly. Best corrected visual acuity (BCVA) was already significantly improved at week 2. Central retinal thickness (CRT), intraretinal and subretinal fluid (SRF) were significantly improved from week 1 onwards. Half of the patients showed nAMD activity at week 2 or 3 and received the first retreatment earlier than 4 weeks after baseline injection. In total, 46% of retreatments were already applied 2 or 3 weeks after the previous treatment. Greater range of CRT and SRF fluctuation during follow-up was associated with lower final BCVA. Lower baseline BCVA and better SRF improvement at week 2 was associated with greater BCVA improvement. In conclusion, high-frequency SD-OCT follow-up provided a good option for adapting treatment in nAMD individually.

Assessment of Reinjection Numbers and Intervals for Diabetic Macular Edema Patients Who Received Dexamethasone Intravitreal Implants in Germany and Switzerland.

PURPOSE: The purpose was to assess the number and intervals of dexamethasone intravitreal implant (DEX) reinjections in a real-world setting for the treatment of diabetic macular edema (DME) and to determine the relationship with effectiveness and safety. PATIENTS AND METHODS: Data were abstracted from medical records of DME patients in Germany and Switzerland for this retrospective, multicenter, drug utilization study. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) changes 7-12 weeks post-injection(s) measured effectiveness. Adverse events (AEs) of special interest were reported. RESULTS: A total of 141 patients, 108 from Germany and 33 from Switzerland, were assessed. Mean (SD) reinjection interval was 5.7 (4.2) months. Mean baseline BCVA was 61.6 letters, and mean baseline CRT was 413.3 µm. The mean BCVA and CRT changes at 7-12 weeks after baseline, reinjection 1, 2, and 3 were +3.4, +3.7, +3.2, and -1.4 letters and -88.3, -81.6, -102.4, and -124.1 µm, respectively. The Spearman correlation between change in BCVA and CRT and DEX reinjection interval was r=0.03 (P=0.66) and r=0.07 (P=0.38), respectively. Only 18% of patients experienced at least 1 AE. CONCLUSION: There was no statistically significant correlation between drug effectiveness and reinjection intervals in either country. Although these results are preliminary, they indicate that DEX improves BCVA and CRT in real-world clinical practice.