Photocoagulation or sham laser in addition to conventional anti-VEGF therapy in macular edema associated with TelCaps due to diabetic macular edema or retinal vein occlusion (TalaDME): a study protocol for a multicentric, French, two-group, non-commercial, active-control, observer-masked, non-inferiority, randomized controlled clinical trial.

BACKGROUND: Macular edema (ME) results from hyperpermeability of retinal vessels, leading to chronic extravasation of plasma components into the retina and hence potentially severe visual acuity loss. Current standard of care consists in using intravitreal injections (IVI), which results in a significant medical and economic burden. During diabetic retinopathy (DR) or retinal vein occlusion (RVO), it has recently been shown that focal vascular anomalies (capillary macro-aneurysms, also termed TelCaps) for telangiectatic capillaries may play a central role in the onset, early recurrence, and/or persistence of ME. Since targeted photocoagulation of TelCaps may improve vision, identification, and photocoagulation of TelCaps, it may represent a way to improve management of ME. OBJECTIVE: The Targeted Laser in (Diabetic) Macular Edema (TalaDME) study aims to evaluate whether ICG-guided targeted laser (IGTL), in association with standard of care by IVI, allows reducing the number of injections during the first year of treatment compared with IVI only, while remaining non-inferior for visual acuity. METHODS: TalaDME is a French, multicentric, two-arms, randomized, sham laser-controlled, double-masked trial evaluating the effect of photocoagulation of TelCaps combined to IVI in patients with ME associated with TelCaps. Patients with vision loss related to center involved ME secondary to RVO or DR and presenting TelCaps are eligible. Two hundred and seventy eyes of 270 patients are randomized in a 1:1 ratio to standard care, i.e., IVI of anti-VEGF solely (control group) or combined with IGTL therapy (experimental group). Stratification is done on the cause of ME (i.e., RVO versus diabetes). Anti-VEGF IVI are administered to both groups monthly for 3 months (loading dose) and then with a pro re nata regimen with a monthly follow-up for 12 months. The primary endpoint will be the number of IVI and the change in visual acuity from baseline to 12 months. Secondary endpoints will be the changes in central macular thickness, impact on quality of life, cost of treatment, and incremental cost-utility ratio in each groups. KEY SAFETY: Rare but severe AE linked to the use of IVI and laser, and previously described, are expected. In the sham group, rescue laser photocoagulation may be administered by the unmasked investigator if deemed necessary at month 3. DISCUSSION: The best management of ME associated with TelCaps is debated, and there have been no randomized study designed to answer this question. Given the fact that TelCaps may affect 30 to 60% of patients with chronic ME due to DR or RVO, a large number of patients could benefit from a specific management of TelCaps. TalaDME aims to establish the clinical and medico-economic benefits of additional targeted laser. The results of TalaDME may raise new recommendations for managing ME and impact healthcare costs. TRIAL REGISTRATION: EudraCT: 2018-A00800-55/ NCT03751501. Registration date: Nov. 23, 2018.

Patient Experience Survey of Anti-Vascular Endothelial Growth Factor Treatment for Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema.

INTRODUCTION: Understanding patient perspectives of treatment may improve adherence and outcomes. This study explored real-world patient experiences with anti-vascular endothelial growth factor (anti-VEGF) treatment for diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD). METHODS: This multinational, non-interventional, quantitative, cross-sectional, observational survey assessed treatment barriers/burden, patient-reported visual functioning, and treatment satisfaction in DME and nAMD patients in the USA, the UK, Canada, France, Italy, and Spain. Treatment patterns and visual outcomes were extracted from medical charts. Regression models evaluated relationships between adherence, total missed visits, number of anti-VEGF injections, and clinical and patient-reported outcomes for visual functioning. Association between treatment satisfaction and aspects of burden were assessed. RESULTS: The survey was completed by 183 DME and 391 nAMD patients. Patients had moderately high vision-related functioning (25-item National Eye Institute Visual Functioning Questionnaire score: mean = 74.8) and were satisfied with their current treatment (mean total score: Macular Disease Treatment Satisfaction Questionnaire = 59.2; Retinopathy Treatment Satisfaction Questionnaire = 61.3). Treatment satisfaction scores were worse with higher time-related impacts of treatment (nAMD/DME), higher impacts on finances and daily life (nAMD), negative impacts on employment and lower expectations for treatment effectiveness (DME). Most patients reported ≥1 barrier (66.1% DME, 49.2% nAMD patients) related to treatment (35.0%), clinic (32.6%), and COVID-19 (21.1%). Moreover, 44.9% of patients reported some impairment in activities of daily living. Work absenteeism was observed among >60% of working patients. Nearly one-quarter (24.2%) of patients needed ≥1 day to recover from intravitreal injections; most reported ≥30 min of travel time (73.7%) and clinic wait time (54.2%). In unadjusted univariable analyses, treatment adherence (vs. nonadherence) was related to higher most recent visual acuity (ß = 8.98 letters; CI, 1.34-16.62) and lower odds of visual acuity below driving vision (≤69 letters) (OR = 0.50; CI, 0.25-1.00). CONCLUSION: More durable treatments with reduced frequency of injections/visits may reduce treatment burden and improve patient satisfaction, which may enhance adherence and visual outcomes.

Real-World Management of Macular Edema Secondary to Retinal Vein Occlusion with Intravitreal Aflibercept: 24-month Results from the AURIGA Observational Study.

INTRODUCTION: AURIGA is the largest real-world study to date to evaluate intravitreal aflibercept (IVT-AFL) treatment of diabetic macular edema or macular edema secondary to retinal vein occlusion (RVO) in routine clinical practice. Here, we report the 24-month outcomes in the RVO cohort from France, Germany, Italy, and Taiwan. METHODS: AURIGA (NCT03161912) was a prospective observational study. Eligible patients with RVO were enrolled for whom the decision to treat with IVT-AFL had already been made by the attending physician. Patients were treated with IVT-AFL for up to 24 months at physician discretion according to local practice. The primary endpoint was mean change in visual acuity (VA; Early Treatment Diabetic Retinopathy Study [ETDRS] letters) from baseline to month (M) 12. All statistical analyses were descriptive. RESULTS: In 554 treatment-naïve and 65 previously treated patients with RVO, the respective mean (95% confidence interval) change in VA from baseline was + 12.5 (10.8, 14.3) and + 7.9 (3.3, 12.6) letters by M12 and + 11.4 (9.4, 13.3) and + 4.4 (- 0.6, 9.5) letters by M24 (baseline mean ± standard deviation: 51.0 ± 21.9 and 51.9 ± 20.4 letters); 44.0% of treatment-naïve and 27.9% of previously treated patients reported ≥ 15-letter gains by M24. By M24, the mean change in central retinal thickness from baseline was - 247 (- 267, - 227) µm in treatment-naïve patients and - 147 (- 192, - 102) µm in previously treated patients. From baseline to M6, M12, and M24, treatment-naïve patients received a total of 4.0 ± 1.3, 5.5 ± 2.5, and 6.9 ± 4.2 injections, respectively, and previously treated patients received 3.8 ± 1.5, 5.0 ± 2.2, and 6.3 ± 3.7 injections, respectively. The safety profile of IVT-AFL was consistent with that of previous studies. CONCLUSIONS: In AURIGA, patients with RVO experienced clinically relevant functional and anatomic improvements following IVT-AFL treatment in routine clinical practice. These improvements were largely maintained in treatment-naïve patients over the 24-month study despite the decreasing treatment frequency, suggesting long-term durability of IVT-AFL treatment outcomes. Infographic available for this article. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03161912 (May 19, 2017). INFOGRAPHIC.

Intravitreal Aflibercept for the Treatment of Diabetic Macular Edema in Routine Clinical Practice: Results from the 24-Month AURIGA Observational Study.

INTRODUCTION: AURIGA is the largest real-world study to date to evaluate intravitreal aflibercept (IVT-AFL) in the treatment of diabetic macular edema (DME) or macular edema secondary to retinal vein occlusion in routine clinical practice. The 24-month outcomes in the DME cohort from across 11 participating countries are reported here. METHODS: AURIGA (NCT03161912) was a prospective observational study. The study enrolled eligible patients with DME for whom the decision to treat with IVT-AFL had previously been made by the attending physician. Patients were treated with IVT-AFL for up to 24 months at physician discretion according to local practice. The primary endpoint was mean change in visual acuity (VA; Early Treatment Diabetic Retinopathy Study [ETDRS] letters) from baseline to month 12 (M12). All statistical analyses were descriptive. RESULTS: In 1478 treatment-naïve and 384 previously treated patients with DME, the mean (95% confidence interval) change in VA from baseline was +6.7 (5.7, 7.6) and +7.4 (5.5, 9.4) letters by M12 and +5.9 (4.9, 6.9) and +8.1 (6.1, 10.1) letters by M24 (baseline [mean ± standard deviation]: 56.0 ± 19.8 and 50.8 ± 19.5 letters), respectively; 25.9% of treatment-naïve and 32.8% of previously treated patients achieved ≥ 15-letter gains by M24. The mean change in central retinal thickness from baseline to M24 was -110 (-119, -102) µm in treatment-naïve patients and -169 (-188, -151) µm in previously treated patients. By M6, M12, and M24, treatment-naïve patients had received 3.8 ± 1.7, 4.9 ± 2.8, and 5.7 ± 3.9 injections, respectively, and previously treated patients had received 3.9 ± 1.5, 4.9 ± 2.4, and 6.2 ± 3.6 injections, respectively. The safety profile of IVT-AFL was consistent with previous studies. CONCLUSION: In AURIGA, treatment-naïve and previously treated patients with DME achieved clinically relevant functional and anatomic improvements following IVT-AFL treatment for up to 24 months in routine clinical practice. Even with the decreasing injection frequency observed, these gains were largely maintained throughout the study, suggesting long-term durability of the positive effects of IVT-AFL treatment. Infographic available for this article. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03161912 (May 19, 2017). INFOGRAPHIC.

LONGITUDINAL ANALYSIS OF MICROVASCULAR CHANGES IN SICKLE CELL DISEASE USING SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To analyze the changes in macular vascular densities (VDs) and foveal avascular zone (FAZ) over a 6-year period using swept-source optical coherence tomography angiography in patients with sickle cell disease compared with unaffected control subjects. METHODS: Thirty eyes of patients with sickle cell disease and 12 eyes of unaffected control subjects matched for age and ethnicity were examined at a 6-year interval using the same imaging protocol, including ultra-wide-field angiography, swept-source OCT, and 3 × 3-mm optical coherence tomography angiography. The macular VD and FAZ were measured on ImageJ software according to previously reported algorithms. RESULTS: In sickle cell eyes, the mean FAZ significantly increased ( P < 0.01), and the VD decreased in the foveal (within a circle of 1.5 mm in diameter around the foveal center) and temporal areas in both the superficial and the deep capillary plexuses ( P < 0.01). The VD did not change over time in the parafoveal area (annulus between two circles of 1.5 and 3 mm in diameter) and in the superior, inferior, and nasal sectors. No worsening of peripheral retinopathy was observed in the cohort during the follow-up, except for one eye that developed sea-fan. In the control eyes, no microvascular change was observed over time in FAZ size and VD. CONCLUSION: These longitudinal optical coherence tomography angiography findings in patients with sickle cell disease showed an enlargement of the FAZ and a decrease in VD in the temporal and perifoveal regions despite the absence of progression of peripheral retinopathy, suggesting a worsening of the macular nonperfusion over time in sickle cell disease.

Proliferative Sickle Cell Retinopathy in the Retinal Periphery Detected by Ultra-Widefield Imaging: A Case Report.

Sickle cell proliferative retinopathy usually presents first in the peripheral retina and the ability to extend and enhance our visualization of the peripheral retina would allow for superior clinical decision-making. In our practice, we had a 28-year-old patient diagnosed with major sickle cell disease of the homozygous type SS (HbSS) that presented with sickle cell proliferative retinopathy detected by ultra-widefield imaging in the nasal side of the left fundus. At follow-up, neovascularization was detected in the extreme nasal periphery of the left eye by ultra-widefield imaging fluorescein angiography with right gaze. The case was graded as Goldberg stage 3, and the patient was administered photocoagulation treatment. With further advancements in the quality and modality of peripheral retinal imaging, novel proliferative lesions can be detected and appropriately managed much earlier than was previously possible. Ultra-widefield imaging allows for the visualization of the central 200 degrees of the retina but, with gaze view, peripheral retina beyond 200 degrees can be reached.

LONG-TERM PROGNOSIS OF CHOROIDAL NEOVASCULARIZATION COMPLICATING ANGIOID STREAKS.

PURPOSE: To report the very long-term visual prognosis of choroidal neovascularization complicating angioid streaks in the antivascular endothelial growth factor era. METHODS: Retrospective monocentric study aimed at analyzing patients' demographics, choroidal neovascularization features, angioid streak-associated conditions, and previous and current therapies for choroidal neovascularization. The main outcome measures were the quantitative measurement of central retinal pigment epithelial atrophy enlargement by comparing the ratio of pixels involved on automated infrared images acquired by spectral-domain optical coherence tomography and the changes in best-corrected visual acuity. The secondary outcome measures were the number of intravitreal injections and the changes in central choroidal thickness and central retinal thickness. Subgroup analyzes were performed to compare macular atrophy extent between eyes of patients with or without proven pseudoxanthoma elasticum ("PXE" or "no PXE") and between eyes previously treated or not with photodynamic therapy ("PDT" or "no PDT"). RESULTS: Thirty-three eyes of 23 patients were included. The mean best-corrected visual acuity decreased significantly from 66 ± 19 Early Treatment Diabetic Retinopathy Study letters at the time of the first antivascular endothelial growth factor injection to 52 ± 23 Early Treatment Diabetic Retinopathy Study letters at the end of the follow-up (mean follow-up duration: 109 ± 42 months, range: 47-175 months). The ratio of central retinal pigment epithelial atrophy enlargement was 201%, 110%, 240%, and 111% in the PXE, no PXE, PDT, and no PDT groups, respectively. CONCLUSION: Despite the use of antivascular endothelial growth factor agents, the very long-term prognosis appeared relatively poor, especially in patients with PXE. This study also suggests that PDT should be used with caution in the management of choroidal neovascularization in eyes with angioid streaks.

Ultra-Wide-Field Fluorescein Angiography Assessment of Non-Perfusion in Patients with Diabetic Retinopathy Treated with Anti-Vascular Endothelial Growth Factor Therapy.

Purpose: To follow the evolution of peripheral ischemia by fluorescein angiography (FA) on ultra-wide-field (UWF) images in diabetic patients treated with anti-vascular endothelial growth factor (anti-VEGF) for macular edema. Methods: Prospective, non-interventional cohort study analyzing UWF-FA images of 48 patients with diabetic retinopathy (48 eyes) treated for diabetic macular edema. UWF-FA was performed at baseline and after one year of anti-VEGF therapy (M12). The primary endpoint was the change in the non-perfusion index. Results: Of the 48 patients included in this study, 25 completed the one-year follow-up, and 20 had FA images of sufficient quality to be interpreted. The non-perfusion index did not significantly change from baseline after one year of anti-VEGF treatment (0.7% of the non-perfused area at baseline versus 0.5% at M12; p = 0.29). In contrast, the diabetic retinopathy severity score improved significantly between baseline and M12. Conclusions: Anti-VEGF treatment with aflibercept for diabetic macular edema had no impact on the retinal perfusion assessed by FA, but it allowed for artificially improving diabetic retinopathy severity scores.

Two-year outcomes of the APOLLON observational study of intravitreal aflibercept monotherapy in France in patients with diabetic macular edema.

APOLLON (NCT02924311) was a prospective observational study to evaluate the effectiveness of intravitreal aflibercept (IVT-AFL) treatment of diabetic macular edema (DME) over 24 months in routine clinical practice in France. The primary endpoint was mean change from baseline in best-corrected visual acuity (BCVA; Early Treatment Diabetic Retinopathy Study letters) by 12 months, and safety was monitored throughout the study. Of 402 patients enrolled across 61 participating clinics and hospitals in France, 168 patients were followed for at least 24 months and included in the effectiveness analyses (79 treatment-naïve and 89 previously treated). After 24 months of IVT-AFL treatment, the mean (± standard deviation [SD]) change in BCVA from baseline was + 6.5 (± 10.7) letters in treatment-naïve patients (p < 0.001) and + 1.6 (± 17.0) letters in previously treated patients (p = 0.415) from a baseline of 63.8 (± 13.6) and 60.5 (± 16.5) letters. The mean number of IVT-AFL treatments over 24 months was 11.3 (± 4.9) and 11.9 (± 4.7) for treatment-naïve and previously treated patients. This final analysis of the APOLLON study indicated that following 24 months of IVT-AFL treatment in routine clinical practice in France, treatment-naïve patients with DME achieved significant gains in visual acuity and previously treated patients maintained prior visual acuity gains.Trial registration number: NCT02924311.

Multimodal Imaging of Unilateral Acute Maculopathy Associated with Hand, Foot, and Mouth Disease: A Case Series.

We described clinical and multimodal imaging findings in 4 patients with unilateral acute idiopathic maculopathy (UAIM) associated with hand, foot, and mouth disease. Four eyes of 4 patients (3 women and 1 man) with a mean age of 35 years (range: 24-40 years) were included. A bacillary detachment was observed in 3 out of the 4 eyes and was strongly suspected in the remaining eye. This particular detachment was resolved within 5-10 days in our series. A choriocapillaris involvement was supported by the multimodal imaging findings. On indocyanine green angiography, a hypofluorescence was observed throughout the sequence, and OCT angiography showed a defect of the choriocapillaris perfusion. In this case series, a complete multimodal retinal assessment allowed identifying the choriocapillaris as the primary tissue involved in UAIM associated with coxsackie virus infection. In 3 out of our 4 cases, a bacillary detachment with a transient evolution was identified.

Macular toxicity of vital dye after pars plana vitrectomy for idiopathic epiretinal membrane: A case report.

Purpose: To describe the first reported case of outer retinal damage following the use of Membrane Blue Dual for epiretinal membrane (ERM) surgery. Observations: A 74-year-old female underwent pars plana vitrectomy and ERM peeling assisted with Membrane Blue Dual for an idiopathic ERM. Postoperatively, the patient reported a decline in visual acuity with a central scotoma. Fundus examination revealed a well-defined retinal whitening in the peeling area which evolved into pigmentary changes as confirmed by fundus autofluorescence. Optical coherence tomography (OCT) showed loss of outer retinal layers and irregular mottling of the retinal pigment epithelium. Fundus and OCT appearance remained unchanged after 4 months and the central scotoma also persisted. Conclusions and Importance: ERM surgery assisted with Membrane Blue Dual can induce major changes in retinal pigment epithelium and outer retinal layers. This adverse event which probably results from combined light and dye toxicity should be considered by all surgeons even though its occurrence is rare.

Drivers of and Barriers to Adherence to Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema Treatment Management Plans: A Multi-National Qualitative Study.

Purpose: Neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) patients treated with intravitreally injected anti-vascular endothelial growth factor (anti-VEGF) monotherapies achieve lower vision improvements compared with patients in clinical trials. This qualitative research study aimed to better understand the real-world anti-VEGF treatment experience from nAMD and DME patients', caregivers', and retina specialists' perspectives. Methods: One-time, semi-structured, individual interviews were conducted with adult patients with nAMD or DME treated with anti-VEGF injections for ≥12 months, their caregivers, and experienced retina specialists. Interview transcripts were analyzed qualitatively using a thematic analysis approach. Results: A total of 49 nAMD and 46 DME patients, 47 nAMD and 33 DME caregivers, and 62 retina specialists were interviewed in the USA, Canada, France, Germany, Italy and Spain. Most (79%) patients and caregivers reported disruptions to their routine on the day before, the day of, or the day after anti-VEGF injection. Seven nAMD patients (14%) and 14 DME patients (30%) reported having missed an injection visit. The most frequently reported driver for adherence for patients was the doctor-patient relationship (n=66, 70%), whereas for caregivers, it was the ease of booking an appointment (n=25, 32%). Retina specialists reported patient education on the treatment (n=28, 45%) as the most important driver. Treatment barriers could be grouped into four categories: tolerability, clinical factors, logistical parameters and human factors. The most frequently reported barrier to adherence for patients and caregivers was related to side effects (pain/discomfort/irritation: n=63, 67% of patients; n=52, 66% of caregivers), whereas for retina specialists it was logistical parameters (travel logistics: n=44, 71%). Conclusion: This study highlights the importance of the doctor-patient relationship and patient education as key drivers, and treatment tolerability and logistics as key barriers to treatment adherence. Improved doctor-patient relationship/communication and patient education together with new therapies offering convenience, long-acting effectiveness, and better tolerability may improve treatment adherence.

Comparison of Ultra-Wide Field Photography to Ultra-Wide Field Angiography for the Staging of Sickle Cell Retinopathy.

Sickle cell retinopathy (SCR) is classified by Goldberg based on peripheral vascular changes. Ultra-wide field (UWF) imaging has enhanced visualization of the peripheral retina. However, there is no consensus on the optimal imaging technique for the screening of SCR. We performed a monocentric observational cross-sectional study to compare UWF fundus photography (UWF-FP) with UWF angiography (UWF-FA). All patients who underwent UWF-imaging (Optos, PLC, Scotland, UK) for screening of sickle cell retinopathy between January 2016 and December 2019 were retrospectively included. Eyes with previous laser treatment or concomitant retinal disease were excluded. UWF-FP images were graded based on the Goldberg classification by four graders with various degrees of experience. UWF-FA pictures were reviewed by an independent retina specialist. Differences in Goldberg staging across UWF-FP and UWF-FA were assessed. A total of 84 eyes of 44 patients were included. Based on UWF-FA, most eyes were stage 2 (77.4%) and 19 were stage 3 (22.6%). The pre-retinal neovascularization detection sensitivity on UWF-FP was 52.6 to 78.9%, depending on the graders. UWF-FA led to a later Goldberg stage of retinopathy, in most cases from stage 1 to stage 2. Neovascularization (stage 3) was not detected by our graders on UWF-FP in 21.1 to 57.9% of eyes. UWP-FP tends to underestimate Goldberg stages of retinopathy compared with UWF-FA and is less accurate when detecting neovascularization in sickle cell retinopathy, which has a direct impact on therapeutic management and prognosis.

Incidence and characteristics of rhegmatogenous retinal detachment during coronavirus-19 pandemic: A French study.

PURPOSE: To assess the impact of the Covid-19 pandemic and subsequent lockdown on the number and clinical characteristics of patients with retinal detachment (RD) in a French public university eye hospital. METHODS: Single-center, retrospective non-interventional study. Patients consulting at the emergency room (ER) of Quinze-Vingts Hospital (France) for rhegmatogenous RD before and after instauration of the lockdown were reviewed. We compared the characteristics of patients with RD between the containment period (March17th - April27th,2020) and the period preceding the lockdown (February18th - March16th,2020). We compared the number of RD surgeries performed between the first month of lockdown (March17th - April19th,2020) and the corresponding period of 2019. Number of cases, delay between diagnosis and surgery, visual acuity was measured. RESULTS: During the first month of lockdown, 59 RDs were operated on, compared to 107 in the corresponding period in 2019 (-44,8%). Mean time from first symptoms to surgery was significantly higher during the lockdown 12.7 (11.3) days vs 7.6 (7.8) days (p = 0.031) before. During the lockdown, the mean BCVA was lower albeit the difference did not reach statistical significance (1.16 (0.9) during pre-containment vs 1.5 (0.9) during containment; p = 0.09). Reasonsfor delayed consultation were: fear of Covid-19 (31%; p = 0.0001), absence of referral doctor (31%; p = 0.003) and difficulties in getting to public transport (10.3%;p = 0.859). CONCLUSION: Despite maintaining accessto emergency eye care facilitiesin our hospital, the lockdown affected visual health. Should the lockdown be reinstated, we postulate that a better information about eye care access for non-Covid emergencies may attenuate its effect on visual health.

Reduced Vessel Density in the Mid-Periphery and Peripapillary Area of the Superficial Capillary Plexus in Non-Proliferative Diabetic Retinopathy.

Our aim in this study was to assess the vessel density (VD) and vessel skeleton density (VSD) in the nasal area of the superficial capillary plexus (SCP) of diabetic subjects without diabetic retinopathy (DR), or in those with a non-proliferative diabetic retinopathy (NPDR), and to evaluate the relationship between the VD and VSD and the severity of DR. In this prospective study, the VD and VSD in the SCP were measured and analyzed on 6 × 6-mm macular and nasal optical coherence tomography angiography scans. The three concentric circles of the Early Treatment of Diabetic Retinopathy Study (ETDRS) grid were used and divided into zones numbered from 1 to 9 in the macular area and from 1 to 8 in the nasal area. The VD was significantly lower in the nasal peripapillary area (p = 0.0028), and both the VD and VSD were significantly lower in the macular area (p = 0.0131 and p = 0.0132, respectively) in patients with more severe DR. The SD was significantly lower in zones 5 (p = 0.0315) and 6 (p = 0.0324) in the nasal grid in patients with more severe DR. We showed a lower superficial capillary flow in the nasal periphery and peripapillary area in patients with more severe DR.

Efficacy and safety of intravitreal aflibercept in ranibizumab-refractory patients with neovascular age-related macular degeneration.

BACKGROUND: Anti-vascular endothelial growth factor (anti-VEGF) agents have become the standard of care in neovascular age-related macular degeneration (nAMD). Despite generally excellent response rates to anti-VEGF therapy, some patients do not respond or may respond suboptimally. In the case of refractory or rapidly recurring fluid in nAMD, clinicians may switch to another anti-VEGF agent. TITAN was an observational study that assessed the effectiveness and safety of intravitreal aflibercept (IVT-AFL) in patients with nAMD refractory to ranibizumab who switched to IVT-AFL after less than 12 months of ranibizumab treatment in routine clinical practice in France. METHODS: TITAN was an observational, retrospective and prospective 12-month study conducted at 28 centres in France. Patients with nAMD refractory to ranibizumab were enrolled. Patients who were switched from ranibizumab to IVT-AFL were followed for 12 months. Data were obtained from medical records for retrospectively included patients, and at routine follow-up visits for those included prospectively. The main outcome measure was percentage of patients who achieved treatment success (gain of ≥1 Early Treatment Diabetic Retinopathy Study letters in best-corrected visual acuity [BCVA] and/or any reduction in central retinal thickness [CRT]) from baseline to 12 months after switching. A sample size of 225 patients was determined based on a 2-sided 95% confidence interval with a width equal to 0.12 when the sample proportion was 0.70. RESULTS: We analysed safety data (N = 217) and clinical outcomes from patients in the per-protocol population (n = 125). The mean (standard deviation) number of IVT-AFL injections was 7.5 (2.6). Treatment success was achieved in 68.8% of patients. Mean BCVA change from baseline to Month 12 was + 1.5 letters (P = 0.105) and the mean CRT change was - 45.0 µm (P <  0.001). In a subgroup analysis, in patients who received three initial monthly IVT-AFL injections, mean BCVA gain was 3.3 letters at Month 12 (P = 0.015). Excluding lack of efficacy and inappropriate scheduling of drug administration, the most common adverse event was eye pain (2.3%). CONCLUSIONS: Switching ranibizumab-refractory patients with nAMD to IVT-AFL may improve visual outcomes in some patients, particularly those who receive three initial monthly injections. TRIAL REGISTRATION: ClinicalTrials.gov , NCT02321241 . First posted: December 22, 2014; Last update posted: July 2, 2018.

Lung ultrasound is a reliable diagnostic technique to predict abnormal CT chest scan and to detect oxygen requirements in COVID-19 pneumonia.

COVID-19 pneumonia can be severe, with an unpredictable evolution and high mortality prevalence in older patients. The diagnosis is usually performed by RT-PCR or CT chest scan. Lung ultrasonography (LUS) has been proposed as an alternative method to monitor patients with COVID-19 pneumonia. To assess the diagnostic performance of LUS, we performed LUS using a portable device and adapting a protocol already used in Acute Respiratory Syndrome. We used the score obtained with the index we created to assess for LUS diagnostic performance as compared to lung CT chest scan and to predict for oxygen requirements. Daily bedside LUS was easy to perform and microbiologically safe. LUS was 89% sensitive and 100% specific in predicting CT chest scan abnormalities, and 95% sensitive and 67% specific in detecting oxygen requirements. This is the first report on the diagnostic performance of LUS as compared to CT chest scan for the diagnosis of COVID-19 pneumonia and assessments of oxygen requirements by LUS. LUS could help in the orientation of dyspneic patients to intensive care. It could also be proposed when there is limited access to CT scan in the context of a pandemic crisis, or to implement clinical lung examinations for outpatient follow-up.

Comparison of the Effect of Ranibizumab and Aflibercept on Changes in Macular Choroidal Thickness in Patients Treated for Diabetic Macular Edema.

PURPOSE: The aim of this study was to assess the effect of intravitreal injections (IVI) of ranibizumab and aflibercept on the choroidal thickness (CT) in patients with treatment-naive diabetic macular edema (DME) before and after monthly IVI. Patients and Methods. Prospective monocenter study. Inclusion criteria were treatment-naive DME eyes without concomitant panretinal photocoagulation, associated with a decrease in best-corrected visual acuity ≤75 letters on the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. DME was defined by a central retinal thickness ≥300 µm on swept-source OCT (Triton DRI OCT, Topcon Corporation, Itabashi, Japan). Patients received 5 IVI of ranibizumab or aflibercept. The primary endpoint was the change in the central subfield CT (CSCT) between inclusion (M0) and 1 month after the fifth IVI (M5). The secondary endpoint was the CT changes between M0 and M5 in other locations of the macular ETDRS grid. RESULTS: Twenty-four eyes of 24 patients with a mean age of 61.1 years were included. Eleven and 13 patients were, respectively, treated with ranibizumab and aflibercept, and 86.4% had type 2 diabetes. The overall CSCT decreased significantly by -12 µm between M0 and M5 (231.7 µm at M0 and 219.7 µm at M5) (p=0.03). It decreased by -15.2 µm (p=0.02) in the aflibercept group (206.9 µm at M0 and 191.7 µm at M5) and by -7.3 µm (p=0.4) in the ranibizumab group (267.5 µm at M0 and 260.2 µm at M5). The CSCT decreased by -4.9 µm in noninjected contralateral eyes (242.3 µm at M0 and 237.4 µm at M5). CT changes between M0 and M5 in the superior, temporal, inferior, and nasal macular inner ring were significant in the aflibercept group but not in the ranibizumab and control groups. CONCLUSION: In DME patients, the CSCT decreases after 5 IVI of anti-VEGF, especially after aflibercept treatment.

Analysis of the foveal microvasculature in sickle cell disease using swept-source optical coherence tomography angiography.

Ischemic microangiopathy was clearly identified in sickle cell disease (SCD) using fluorescein angiography. A prospective observational clinical study was conducted to assess the foveal avascular zone (FAZ) area and explore perifoveal microvasculature changes in the superficial (SCP) and deep (DCP) capillary plexus using optical coherence tomography angiography (OCTA) and compare two genotypes-HbS/HbS (HbSS) and HbS/HbC (HbSC)-to control. All consecutive patients with electrophoretic confirmation of SCD were included. Swept-source OCTA scans (Triton Plus, Topcon, Tokyo, Japan) with a 3 × 3-mm scanning area and ultra-wide field (UWF) retinography (California, Optos, Fife, Scotland) were recorded for all patients. For OCTA analysis, preset parameters were used to segment the SCP and DCP. The FAZ area was manually assessed. The number of vascular branching points was automatically assessed based on the vascular skeletonization using ImageJ software. Eyes were staged based on Goldberg's classification of SCD retinopathy (SCDR) using UWF imaging. Forty-six eyes of 24 patients were included in the HbSS (n = 27) and HbSC (n = 19) groups and 16 eyes of 8 unaffected patients in a control group. In the DCP, the FAZ was significantly larger in the HbSC (p = 0.0001) and HbSS (p = 0.0004) groups compared to controls. The FAZ area in the SCP, CRT and number of superficial vascular branching points did not significantly differ between both genotypes. There were less branching points in the HbSC (p = 0.034) and HbSS (p = 0.0014) groups than in controls. The Goldberg stage was significantly higher in the HbSC group than in the HbSS group (2.21 vs. 1.22, p = 0.0062). OCTA provides useful information on macular microvasculature and structural alterations associated with SCDR. Ischemic abnormalities are more predominant in the DCP in case of SCDR and no difference was found between genotypes of patients visually asymptomatic.

Ethnic differences in normal retinal capillary density and foveal avascular zone measurements.

BACKGROUND: The purpose of this study was to quantify retinal capillary density and foveal avascular zone (FAZ) area in healthy subjects according to their ethnicity, using optical coherence tomography angiography (OCTA). METHODS: In this cross-sectional study, all eyes underwent swept-source OCTA (Triton, Topcon, Tokyo, Japan). Macular OCTA scans (3 × 3 mm) were obtained in healthy white Caucasian and black African subjects. The FAZ area and capillary density in both the superficial (SCP) and deep capillary plexuses (DCP) were automatically measured using a custom-made software combining vessel binarization and skeletonization. RESULTS: Twelve eyes of 12 healthy Caucasians and 15 eyes of 15 healthy black Africans were included in the analysis. The mean FAZ area was significantly smaller, and the overall vessel density (VD) was higher in the SCP and DCP of Caucasians compared to black Africans. The mean FAZ area was 0.26 ± 0.008 mm2 in the SCP and 0.25 ± 0.05 mm2 in the DCP in Caucasians versus 0.33 ± 0.08 mm2 in the SCP (p = 0.01) and 0.37 ± 0.1 mm2 in the DCP (p = 0.03) in Africans. In the SCP and DCP, the mean VD was, respectively, 40.5 ± 0.8% and 47.1 ± 0.5% in Caucasians versus 34.3 ± 1% (p = 0.008) and 40.6 ± 0.9% in Africans (p < 0.001). DISCUSSION/CONCLUSION: In the SCP and DCP, VD is lower in black Africans compared to Caucasians. In OCTA studies on vascular diseases, ethnicity-matched measurements from healthy subjects should be used for comparisons.