Artificial Intelligence-Based Disease Activity Monitoring to Personalized Neovascular Age-Related Macular Degeneration Treatment: A Feasibility Study.

Purpose: To evaluate the performance of a disease activity (DA) model developed to detect DA in participants with neovascular age-related macular degeneration (nAMD). Design: Post hoc analysis. Participants: Patient dataset from the phase III HAWK and HARRIER (H&H) studies. Methods: An artificial intelligence (AI)-based DA model was developed to generate a DA score based on measurements of OCT images and other parameters collected from H&H study participants. Disease activity assessments were classified into 3 categories based on the extent of agreement between the DA model's scores and the H&H investigators' decisions: agreement ("easy"), disagreement ("noisy"), and close to the decision boundary ("difficult"). Then, a panel of 10 international retina specialists ("panelists") reviewed a sample of DA assessments of these 3 categories that contributed to the training of the final DA model. A panelists' majority vote on the reviewed cases was used to evaluate the accuracy, sensitivity, and specificity of the DA model. Main Outcome Measures: The DA model's performance in detecting DA compared with the DA assessments made by the investigators and panelists' majority vote. Results: A total of 4472 OCT DA assessments were used to develop the model; of these, panelists reviewed 425, categorized as "easy" (17.2%), "noisy" (20.5%), and "difficult" (62.4%). False-positive and false negative rates of the DA model's assessments decreased after changing the assessment in some cases reviewed by the panelists and retraining the DA model. Overall, the DA model achieved 80% accuracy. For "easy" cases, the DA model reached 96% accuracy and performed as well as the investigators (96% accuracy) and panelists (90% accuracy). For "noisy" cases, the DA model performed similarly to panelists and outperformed the investigators (84%, 86%, and 16% accuracies, respectively). The DA model also outperformed the investigators for "difficult" cases (74% and 53% accuracies, respectively) but underperformed the panelists (86% accuracy) owing to lower specificity. Subretinal and intraretinal fluids were the main clinical parameters driving the DA assessments made by the panelists. Conclusions: These results demonstrate the potential of using an AI-based DA model to optimize treatment decisions in the clinical setting and in detecting and monitoring DA in patients with nAMD. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Two-year outcomes of intravitreal aflibercept in a Swiss routine treat and extend regimen for patients with neovascular age-related macular degeneration.

The aim of this observational study was to assess the use and outcome of intravitreal aflibercept in a treat and extend regimen in treatment-naïve neovascular AMD patients in routine practice. This both retrospective and prospective study was conducted in four larger Swiss retina clinics (ASTERIA study). The primary endpoint was the mean change in best-corrected visual acuity (BCVA) in ETDRS letters from baseline to 12 months. Between December 2017 and August 2018, 160 patients were included. For patients with available data, the mean change in BCVA was + 8.4 (± 14.4) letters at month 12 (n = 139) and + 5.0 (± 11.4) letters at month 24 (n = 95). A mean number of 8.3 (± 2.4) injections were administered within the first year and 5.4 (± 2.9) injections during the second year. On average, the observed treatment interval at month 12 was 63.3 (± 22.0) days and increased to 69.1 (± 28.6) days at month 24. For 37% of the patients, a treatment interval ≥ 12 weeks was attained at month 24. In conclusion,  intravitreal aflibercept in a Swiss real-life treat and extend regimen resulted in comparable anatomic and functional outcomes as were observed in the prospective registration trials of aflibercept for nAMD treatment.

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.

Ganglion cell layer thickening in well-controlled patients with type 1 diabetes: an early sign for diabetic retinopathy?

PURPOSE: To evaluate early changes in retinal layers using optical coherence tomography (OCT) in patients with long-standing type 1 diabetes (DM1) receiving intensified insulin therapy. METHODS: In a cross-sectional case-control study 150 patients with DM1 and 150 age- and sex-matched healthy control participants underwent OCT imaging. Scans of both eyes were analysed for different layers (NFL, GCL (+IPL), INL, outer layer complex (OLC, including OPL, ONL and ELM) and photoreceptors (PR)) in all subfields of an ETDRS grid. All analyses were performed semi-automatically using custom software by certified graders of the Vienna Reading Center. ANOVA models were used to compare the mean thickness of the layers between patients and controls. RESULTS: Six hundred eyes with 512 datapoints in 49 b-scans in each OCT were analysed. Mean thickness in patients/controls was 31.35 µm/30.65 µm (NFL, p = 0.0347), 76.7 µm/73.15 µm (GCL, p ≤ 0.0001), 36.29 µm/37.13 µm (INL, p = 0.0116), 114.34 µm/112.02 µm (OLC, p < 0.0001) and 44.71 µm/44.69 µm (PR, p = 0.9401). When evaluating the ETDRS subfields separately for clinically meaningful hypotheses, a significant swelling of the GCL in patients could be found uniformly and a central swelling for the OLC, whereas the distribution of NFL and INL thickening suggests that their statistical significance was not clinically relevant. CONCLUSION: These preliminary results demonstrate that preclinical retinal changes in patients with long-standing DM1 can be found by retinal layer evaluation. However, the changes are layer-specific, with significant thickening of the GCL and less so of the OLC suggesting a role as an early sign for diffuse swelling and the evolution of DME even in well-controlled diabetes.

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.

Strongest Correlation Between Contrast Sensitivity and Morphological Characteristics in Bilateral nAMD.

In patients with neovascular age-related macular degeneration (nAMD) there is often an inconsistency between their subjective visual impairment and a still relatively preserved standard Early Treatment of Diabetic Retinopathy Study (ETDRS) best corrected visual acuity. Therefore, in order to better capture the specific functional defects in nAMD, other tests need to be evaluated. In a previous study, we reported contrast sensitivity of the better eye to best correlate with near distance and distance vision related quality of life in patients with bilateral nAMD. Here, we evaluated Pelli-Robson contrast sensitivity, ETDRS visual acuity, low luminance visual acuity and Radner maximum reading speed and correlated them with several morphologic parameters as measured on fundus autofluorescence imaging, optical coherence tomography and optical tomography angiography in 54 patients. A multiple regression analysis was performed which correlated each visual function parameter with the anatomic features. The results showed the strongest correlations between the total area of macular geographic atrophy as well as the percentage of geographic atrophy in the central 1 mm and contrast sensitivity. Further, the regression model selected the total area of macular geographic atrophy, the photoreceptor inner and outer segments interface disruption score, the presence of subretinal fibrosis in the central 1 mm and the central retinal thickness as the variables that explained 71% of the variation in contrast sensitivity when including all eyes. Hence, our results suggest that among the evaluated measures of vision, contrast sensitivity is best correlated with the morphologic impairment in bilateral nAMD. Thus, contrast sensitivity may complement ETDRS visual acuity in clinical trials and serve as a standard diagnostic tool in clinical practice.

The prevalence of retinopathy in patients with type 1 diabetes treated with education-based intensified insulin therapy and its association with parameters of glucose control.

AIM: Prevalence of retinopathy (DR) in patients with type 1 diabetes treated with education-based intensified insulin therapy (EBIIT) and its association with parameters of glucose control. METHODS: 151 patients with mean diabetes duration of 14.3 years [SD ±â€¯5.8]) were analyzed. Eyes were examined using standardized 7 field ETDRS (Early Treatment Diabetic Retinopathy Study) settings and images analyzed by a professional external reading center. The glucose exposure over time was defined as HbA1c years, i.e. the sum of the differences between annual mean HbA1c (in %) minus the ideal HbA1c of 6.0% (42 mmol/mol) for each diabetes year (e.g. HbA1c of 8% (64 mmol/mol) over 6 years gives an excess HbA1c of 2.0% (22 for mmol/mol) for 6 years, resulting in 12 HbA1c years (or 131 for mmol/mol)). RESULTS: The median (interquartile range) of individual mean HbA1c was 7.3% (6.8-7.8) [56 mmol/mol (51-62)]. and the median HbA1c years was 16.8 (9.1-29.1) [183 mmol/mol (99-319)]. No evidence for DR was found in 59 patients (39%), stage 1 DR in 43 (28.5%), stage 2 in 41 (27.2%), stage 3 in 7 (4.6%) and proliferative DR stage 4 in 1 patient. The best correlation between severity of DR and diabetes control measures was found for HbA1c years (Pearson r = 0.41, p < 0.001). CONCLUSIONS: In type 1 diabetes EBIIT is associated with good diabetes control and a low prevalence of DR. The cumulative glucose exposure over time given as HbA1c years is the best predictor for development of DR. ClinicalTrials.gov Identifier: NCT02307110.