Tilted disc in eyes with fovea plana.

PURPOSE: To report the association of tilted disc (TD) with fovea plana. METHODS: Monocentric retrospective study of consecutive eyes diagnosed with fovea plana, assessed by spectral-domain optical coherence tomography. Analysis of the medical charts and imaging findings of patients to collect demographics, the visual acuity, and the clinical context. The presence of associated conditions was checked by two independent readers in order to classify fovea plana as isolated or part of other conditions. RESULTS: Twenty-one patients, 9 men and 12 women, aged 12 to 91 years, were included. Fovea plana was isolated and asymptomatic in 10 (47.6%) patients. In 6 (28.5%) patients, fovea plana was associated with ocular albinism and/or nystagmus. In 6 (28.5%) patients, fovea plana was associated with an obliquity of the optic disc typical of TD, isolated (5 cases), or associated with nystagmus (1 case). CONCLUSION: An association between TD and fovea plana had been reported only once in the literature and had been considered likely coincidental. However, this association could be more common than initially reported and suggests a common pathological process in eye development during embryogenesis.

Final 4-year results of the RAINBOW real-world study: intravitreal aflibercept dosing regimens in France in treatment-naïve patients with neovascular age-related macular degeneration.

PURPOSE: The purpose of this study is to evaluate real-world treatment outcomes in patients with neovascular age-related macular degeneration (nAMD) treated with intravitreal aflibercept (IVT-AFL) in routine clinical practice in France. METHODS: RAINBOW (NCT02279537) was an ambispective, observational, 4-year study assessing IVT-AFL effectiveness, treatment patterns, and safety in patients with nAMD in France. Treatment-naïve patients prescribed IVT-AFL and treated according to local practice (pro re nata or treat-and-extend) were eligible. Three treatment cohorts were retrospectively identified based on their treatment pattern within the first 12 months: regular (3 initial monthly IVT-AFL injections received within 45-90 days after the first injection in month 0 and followed by injections every 2 months), irregular with the initial monthly injections, and irregular without the initial monthly injections. The primary endpoint was mean change in best-corrected visual acuity (BCVA) from baseline to month 12. The 48-month results are described here. RESULTS: Overall, the study included 516 patients (each with one study eye), and 30.2% of patients completed 48 months of IVT-AFL treatment. Mean change in BCVA from baseline (56.5 letters) to month 48 for patients with an assessment at both time points was + 1.1 (regular cohort, n = 47), + 0.1 (irregular cohort with initial monthly injections, n = 115), and - 1.3 letters (irregular cohort without initial monthly injections, n = 26), representing a decrease from the gains achieved at month 12. Mean number of IVT-AFL injections received by month 48 in the treatment cohorts was 14.9, 13.7, and 11.9, respectively. The safety profile of IVT-AFL was consistent with previous studies. CONCLUSION: In RAINBOW, the 48-month results demonstrate a lack of long-term effectiveness of IVT-AFL treatment of nAMD due to progressive undertreatment in routine clinical practice in France. These real-world findings highlight the importance of 3 initial monthly IVT-AFL injections followed by continuous proactive treatment beyond the first year to achieve optimal functional outcomes. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT02279537.

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.

PHOTOBIOMODULATION THERAPY FOR LARGE SOFT DRUSEN AND DRUSENOID PIGMENT EPITHELIAL DETACHMENT IN AGE-RELATED MACULAR DEGENERATION: A Single-Center Prospective Pilot Study.

PURPOSE: To evaluate visual acuity and morphologic changes after photobiomodulation (PBM) for patients affected with large soft drusen and/or drusenoid pigment epithelial detachment associated with dry age-related macular degeneration. METHOD: Twenty eyes with large soft drusen and/or drusenoid pigment epithelial detachment age-related macular degeneration were included and treated using the LumiThera Valeda Light Delivery System. All patients underwent two treatments per week for 5 weeks. Outcome measures included best-corrected visual acuity, microperimetry-scotopic testing, drusen volume, central drusen thickness, and quality of life score at baseline and month 6 (M6) follow-up. Data of best-corrected visual acuity, drusen volume, and central drusen thickness were also recorded at week 5 (W5). RESULTS: Best-corrected visual acuity significantly improved at M6 with a mean score gain of 5.5 letters ( P = 0.007). Retinal sensitivity decreased by 0.1 dB ( P = 0.17). The mean fixation stability increased by 0.45% ( P = 0.72). Drusen volume decreased by 0.11 mm 3 ( P = 0.03). Central drusen thickness was reduced by a mean of 17.05 µ m ( P = 0.01). Geographic atrophy area increased by 0.06 mm 2 ( P = 0.01) over a 6-month follow-up, and quality of life score increased by 3,07 points on average ( P = 0.05). One patient presented a drusenoid pigment epithelial detachment rupture at M6 after PBM treatment. CONCLUSION: The visual and anatomical improvements in our patients support previous reports on PBM. PBM may provide a valid therapeutic option for large soft drusen and drusenoid pigment epithelial detachment age-related macular degeneration and may potentially slow the natural course of the disease.

STELLATE MULTIFORM AMELANOTIC CHOROIDOPATHY: Clinical and Multimodal Imaging Features.

PURPOSE: To describe the clinical and multimodal imaging features of stellate multiform amelanotic choroidopathy (SMACH; also known as serous maculopathy due to aspecific choroidopathy). METHODS: Retrospective observational case series of eyes presenting with SMACH. Multimodal imaging including fundus photography, optical coherence tomography (OCT), OCT angiography (OCTA), and indocyanine green angiography (ICGA) was analyzed. RESULTS: Eighteen eyes from 18 patients (mean age: 28 ± 19 years) were included. The mean follow-up duration was 9 years. Ophthalmoscopy showed a yellowish orange, dendriform choroidal lesion. At presentation, subretinal fluid (SRF) was seen in 10 of 18 cases (56%). Eight patients (44%) showed no evidence of SRF during a mean follow-up of 6 years. Cross-sectional OCT showed hyperreflective fibrous-like changes within the inner choroid with choriocapillaris flow preservation on OCTA. En face OCT showed a hyperreflective choroidal lesion with finger-like projections oriented in a stellate configuration. On ICGA, SMACH showed early and late hypofluorescence. None of the cases showed lesion growth. CONCLUSION: SMACH seems to be a unilateral choroidopathy characterized by distinctive multimodal imaging features. As SRF was absent in some cases, while a dendriform pattern was a consistent finding in all eyes, the authors propose renaming this entity "stellate multiform amelanotic choroidopathy," a name that retains its previous abbreviation "SMACH."

Optical coherence tomography angiography quantification of choriocapillaris blood-flow after half-fluence photodynamic therapy for chronic central serous chorioretinopathy.

PURPOSE: To quantitatively analyze characteristics of choriocapillaris flow using spectral domain optical coherence tomography angiography (SD-OCTA) in eyes with chronic central serous chorioretinopathy (CSC) before and after treatment by photodynamic therapy (PDT). METHODS: Retrospective interventional study. Macular 3X3 SD-OCT scans were analyzed in eyes diagnosed with chronic CSC before and after treatment with half-fluence PDT. The choriocapillaris en face slabs were extracted from the SD-OCTA device after manual segmentation. En face choriocapillaris flow images were compensated with en face choriocapillaris structure images. Phansalkar local thresholding method was then used with a radius of 4 and 8 pixels. Percentage of flow deficits (FD%), number, size, and total area of FDs were computed for comparison, before and after treatment by half-fluence PDT. RESULTS: Mean choriocapillaris FD% before PDT was of 58.36 + / - 11.88 and of 60.82 + / - 11.08 after PDT using radius 4 pixels with no significant difference (p = 0.140). Mean choriocapillaris FD% was of 58.63 + / - 11.08 before PDT and of 60.87 + / - 10.36 after PDT using radius 8 pixels with no significant difference (p = 0.200). Similarly, no significative difference was found in number, size, and total area of FDs, before and after half-fluence PDT, using radius 4 and 8 pixels in patients with chronic CSC. CONCLUSION: Using Phansalkar local thresholding method, quantitative analysis of choriocapillaris with SD-OCTA found no significant change in choriocapillaris flow deficits before and after successful half-fluence PDT in patients with chronic CSC. Therefore, it seems that half-fluence PDT may not alter choriocapillaris perfusion, at least on a relative short-term basis.

FOCAL CHOROIDAL THICKNESS HEMODYNAMICS AS a SIGN OF MACULAR NEOVASCULARIZATION ACTIVITY IN PATHOLOGIC MYOPIA.

PURPOSE: To analyze the relationship between a focal increase of choroidal thickness (ChT) and exudative activity of macular neovascularization (MNV) secondary to pathologic myopia. METHODS: Retrospective analysis including eyes with pathologic myopia presenting with a focally increased ChT underneath active MNV. All patients included were treated, and ChT was measured before and after each intravitreal injection by two experienced ophthalmologists. RESULTS: Fifty-two eyes of 52 patients with myopic MNV (19 men and 33 women) were included in this analysis. ChT at T-1 averaged 51.09 ± 33.56 µ m, whereas at the time of MNV activation (T0), ChT was significantly thicker: 85.11 ± 43.99 µ m ( P < 0.001). After a single intravitreal injection, the ChT significantly decreased to 53.23 ± 34.15 µ m ( P < 0.001). CONCLUSION: This study showed that focal ChT variations may be considered an interesting corollary sign of MNV in high myopic patients, indicating the activity of myopic neovascularization.

Mycotic aneurysm.

Angioinvasive fungal infections of the cerebral vasculature often lead to significant morbidity and mortality. High clinical suspicion and early antifungal therapy could improve outcomes. We describe the fatal case of a patient with a rapidly enlarging cavernous carotid aneurysm due to angioinvasive fungus. This case highlights the challenges in diagnosis and management of this condition.

A new method for quantification and 3D visualization of brain tumor adhesion using slip interface imaging in patients with meningiomas.

OBJECTIVES: To develop an objective quantitative method to characterize and visualize meningioma-brain adhesion using MR elastography (MRE)-based slip interface imaging (SII). METHODS: This retrospective study included 47 meningiomas (training dataset: n = 35; testing dataset: n = 12) with MRE/SII examinations. Normalized octahedral shear strain (NOSS) values were calculated from the acquired MRE displacement data. The change in NOSS at the tumor boundary (ΔNOSSbdy) was computed, from which a 3D ΔNOSSbdy map of the tumor surface was created and the probability distribution of ΔNOSSbdy over the entire tumor surface was calculated. Statistical features were calculated from the probability histogram. After eliminating highly correlated features, the capability of the remaining feature for tumor adhesion classification was assessed using a one-way ANOVA and ROC analysis. RESULTS: The magnitude and location of the tumor adhesion can be visualized by the reconstructed 3D ΔNOSSbdy surface map. The entropy of the ΔNOSSbdy histogram was significantly different between adherent tumors and partially/completely non-adherent tumors in both the training (AUC: 0.971) and testing datasets (AUC: 0.900). Based on the cutoff values obtained from the training set, the ΔNOSSbdy entropy in the testing dataset yielded an accuracy of 0.83 for distinguishing adherent versus partially/non-adherent tumors, and 0.67 for distinguishing non-adherent versus completely/partially adherent tumors. CONCLUSIONS: SII-derived ΔNOSSbdy values are useful for quantification and classification of meningioma-brain adhesion. The reconstructed 3D ΔNOSSbdy surface map presents the state and location of tumor adhesion in a "clinician-friendly" manner, and can identify meningiomas with a high risk of adhesion to adjacent brain parenchyma. KEY POINTS: • MR elastography (MRE)-based slip interface imaging shows promise as an objective tool to preoperatively discriminate meningiomas with a high risk of intraoperative adhesion. • Measurement of the change of shear strain at meningioma boundaries can provide quantitative metrics depicting the state of adhesion at the tumor-brain interface. • The surface map of tumor adhesion shows promise in assisting precise adhesion localization, using a comprehensible, "clinician-friendly" 3D visualization.

INTRARETINAL HYPERREFLECTIVE LINES.

PURPOSE: To report intraretinal hyperreflective lines related to various macular conditions. METHODS: All cases were imaged with color photographs, autofluorescence images, and spectral-domain optical coherence tomography, some with fluorescein and/or indocyanine green angiography. Demographic data, imaging, course and outcome were retrospectively analyzed. RESULTS: Forty-nine eyes of 43 patients (16 men and 27 women) were included. Hyperreflective vertical lines (38 eyes) or curvilinear lines along the Henle fiber layer (11 eyes) were present in association with various macular conditions: adult vitelliform dystrophy or pattern dystrophy (24 eyes) frequently associated with an epiretinal membrane (six eyes) and/or thick choroid (nine eyes), age-related maculopathy or macular degeneration (nine eyes), partial resorption of subretinal or intraretinal hemorrhages (five eyes), idiopathic macular microhole (two eyes), vitreomacular traction (three eyes), multiple evanescent white dot syndrome (three eyes), fundus flavimaculatus (two eyes), and pachychoroid pigment epitheliopathy (one eye). The lines fully vanished in cases of hemorrhages, multiple evanescent white dot syndrome or resolution of vitreomacular traction, but usually persisted with gradual thinning in the other conditions. CONCLUSION: The present series showed that intraretinal hyperreflective lines could occur in various inflammatory, degenerative, or tractional conditions. They could reflect a previously unrecognized reaction to various photoreceptor, Müller cell, and/or retinal pigment epithelium damage.

Consensus Nomenclature for Reporting Neovascular Age-Related Macular Degeneration Data: Consensus on Neovascular Age-Related Macular Degeneration Nomenclature Study Group.

PURPOSE: To establish a process to evaluate and standardize a state-of-the-art nomenclature for reporting neovascular age-related macular degeneration (AMD) data. DESIGN: Consensus meeting. PARTICIPANTS: An international panel of retina specialists, imaging and image reading center experts, and ocular pathologists. METHODS: During several meetings organized under the auspices of the Macula Society, an international study group discussed and codified a set nomenclature framework for classifying the subtypes of neovascular AMD and associated lesion components. MAIN OUTCOME MEASURES: A consensus classification of neovascular AMD. RESULTS: The study group created a standardized working definition of AMD. The components of neovascular AMD were defined and subclassified. Disease consequences of macular neovascularization were delineated. CONCLUSIONS: The framework of a consensus nomenclature system, a definition of AMD, and a delineation of the subtypes of neovascular AMD were developed. Establishing a uniform set of definitions will facilitate comparison of diverse patient groups and different studies. The framework presented is modified and updated readily, processes that are anticipated to occur on a periodic basis. The study group suggests that the consensus standards outlined in this article be used in future reported studies of neovascular AMD and clinical practice.

Impact of optical coherence tomography angiography on the non-invasive diagnosis of neovascular age-related macular degeneration.

PURPOSE: To investigate the changes in imaging tool practice for the diagnosis of neovascular age-related macular degeneration (nAMD). METHODS: Retrospective analysis of consecutive patients diagnosed with nAMD in a tertiary care center, over a 6-month period in 2014, 2016, and 2018. Patient demographics were compared. Imaging modalities used in 2014 were fundus photography, fluorescein angiography (FA), and structural spectral-domain optical coherence tomography (SD-OCT), while OCT-angiography (OCT-A) was available from 2015. Imaging tools used in our practice were compared in the 3 cohorts. RESULTS: The 3 cohorts included 163, 99, and 167 patients, respectively. There was no difference in age or gender (mean age 81.7 years). OCT-A images were analyzable in 60.5% and 89.7% of patients respectively in 2016 and in 2018. In the 3 cohorts, all patients were imaged with fundus photography and structural OCT. FA was performed in 70.2, 28.8, and 22.1% of patients, respectively. CONCLUSION: This study showed a shift in practice of imaging tools used for the diagnosis of nAMD, non-invasive tools being increasingly used as the first-line imaging, and FA as the second-line imaging.

INSIGHTS INTO PERIFOVEAL EXUDATIVE VASCULAR ANOMALOUS COMPLEX.

PURPOSE: To report a series of eight patients with perifoveal exudative vascular anomalous complex imaged with optical coherence tomography angiography and the results of anti-vascular endothelial growth factor therapy or laser photocoagulation. METHODS: Retrospective analysis of demographic data, imaging including color pictures, spectral domain optical coherence tomography, and optical coherence tomography angiography, and fluorescein angiography, course, and outcome. RESULTS: Age at onset ranged from 45 to 84 years (mean ± SD: 68.6 ± 13.7). Five cases were initially misdiagnosed. The perifoveal exudative vascular anomalous complex lesion was unique in seven eyes and located predominantly in the superficial capillary plexus in two eyes, strictly in the deep capillary plexus in two eyes, but observed at the level of both plexi (3 eyes). One patient presented two lesions, one in the superficial capillary plexus and one in the deep capillary plexus. Capillary rarefaction was observed around the lesion in six eyes. Sustainable resolution of exudation could be achieved in 2 patients, one after 2 sessions of focal thermal laser photocoagulation and one after 13 intravitreal injections of anti-vascular endothelial growth factor. CONCLUSION: The present series confirms that perifoveal exudative vascular anomalous complex corresponds to a new entity that differs from other conditions associated with capillary aneurysmal lesions. Visual improvement could be obtained after treatment with focal laser or intravitreal anti-vascular endothelial growth factor agents.

Impact of intravitreal aflibercept dosing regimens in treatment-naïve patients with neovascular age-related macular degeneration: 2-year results of RAINBOW.

BACKGROUND: To review treatment outcomes from real-world data of patients with neovascular age-related macular degeneration (nAMD) treated with intravitreal aflibercept (IVT-AFL) injection. METHODS: RAINBOW (ClinicalTrials.gov, NCT02279537) is an ongoing, observational, 4-year study to monitor the effectiveness and safety of IVT-AFL in patients with nAMD in clinical practice in France. Treatment-naïve patients diagnosed with nAMD who had been prescribed IVT-AFL by their treating physician were eligible. The regimens of interest were regular treatment interval cohort (patients who received three initial monthly IVT-AFL injections followed by regular injections every 2 months) and two irregular treatment interval cohorts (with and without three initial monthly injections). Here we describe results at 24 months in patients according to IVT-AFL treatment regimen. RESULTS: The mean change in best-corrected visual acuity (BCVA) with IVT-AFL from baseline to 24 months was + 3.0 letters in the overall population (P < 0.05 vs baseline). The mean change was positive for the regular and irregular treatment interval cohorts with initial doses (+ 4.9 and + 4.0 letters, respectively; P < 0.05 vs baseline) and negative for the irregular treatment interval cohort without initial doses (- 2.5 letters; P = 0.365 vs baseline) at 24 months. The mean overall number of IVT-AFL injections over 12 and 24 months was 6.0 and 8.8, respectively. The most common ocular adverse events were lack of efficacy (6.3%), vitreous floaters (2.7%), and increased lacrimation (1.7%). CONCLUSIONS: In the real-world RAINBOW study, visual outcomes observed at 24 months were consistent with results from the primary endpoint at 12 months. In this study, treatment-naïve patients who received three initial IVT-AFL doses and regular IVT-AFL treatment over the first 24 months experienced better visual outcomes than patients who received no initial doses and an irregular treatment regimen. TRIAL REGISTRATION: www.ClinicalTrials.gov (NCT02279537). Registered 29 October 2014.

Vascular remodeling of choroidal neovascularization in older myopic patients treated with ranibizumab.

PURPOSE: To investigate morphological changes in myopic choroidal neovascularization (mCNV) using optical coherence tomography-angiography (OCT-A) after treatment with ranibizumab. METHODS: Retrospective analysis of consecutive patients over a 24-month period. All treatment-naïve mCNV were imaged at baseline with color pictures, spectral-domain OCT and OCT-A, and fluorescein angiography in selected cases. CNV morphology was classified at baseline and at 6 months. The CNV lesion surface was also compared. RESULTS: Twenty-nine patients with a mean age of 70.3 ± 10.1 years were included. They received a mean number of 2.65 injections over 6 months. Best-corrected visual acuity improved from 62.2 to 68.5 letters (p = 0.004), with regression of exudation in 24 eyes (82.7%). Baseline CNV was classified into tree-in-bud (16 eyes), medusa (9 eyes), or sea-fan (4 eyes) pattern. At 6 months, no abnormal blood flow was observed in CNV in 13 eyes. Eyes with complete regression or evolution towards an indistinct pattern showed more often a complete regression of exudation than eyes with unchanged pattern (p = 0.007). The mean CNV surface significantly decreased from 0.19 to 0.08 mm2 (p < 0.0001). CONCLUSION: An unchanged pattern was more often associated with exudation persistence, while a complete regression or evolution towards indistinct pattern was always associated with vascular inactivity. However, variable changes in mCNV were observed after anti-VEGF. Thus, OCT-A could be more useful in the diagnosis than in the follow-up of mCNV.

SENSITIVITY OF 840-nm SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN DETECTING TYPE 1 NEOVASCULARIZATION ACCORDING TO THE HEIGHT OF THE ASSOCIATED PIGMENT EPITHELIAL DETACHMENT.

PURPOSE: To evaluate the ability of optical coherence tomography angiography (OCTA) to detect abnormal vascular blood flow in Type 1 neovascularization (NV) with or without significant pigment epithelial detachment (PED). METHODS: Consecutive age-related macular degeneration patients with either treatment-naive or anti-vascular endothelial growth factor-treated Type 1 NV were divided into 2 groups based on the PED height on structural OCT: greater than 250 µm (Group 1) versus less than 250 µm (Group 2). Two independent senior retina specialists analyzed the OCTA images (Zeiss Angioplex OCT, Carl Zeiss AG, Jena, Germany) using the automatic slabs alone (first reader) versus automatic and manual segmentation slabs (second reader). RESULTS: In Group 1, 15 men and 42 women, aged from 51 years to 97 years (mean: 87.5), were included. Optical coherence tomography angiography was able to show an abnormal blood flow suggestive of Type 1 NV in 23 (40.3%) of 57 eyes for the first reader and in 32 (56.1%) of 57 eyes for the second reader. In Group 2, 7 men and 30 women, aged from 60 years to 96 years (mean: 80.2), were included. The first and second readers were able to observe an image suggestive of Type 1 NV in 33/37 (89.2%) and 37/37 (100%) of eyes, respectively. CONCLUSION: The ability of OCTA to detect an abnormal blood flow in Type 1 NV was found to highly depend on the height of the associated PED and the use of manual segmentation slabs. Our results suggest that automatic slabs of OCTA should be interpreted with caution for the diagnosis of vascularized PED. The diagnosis of Type 1 NV using OCTA requires the use of manual segmentation and a multimodal imaging approach, especially when the height of the associated PED is >250 µm.

VASCULAR REMODELING OF CHOROIDAL NEOVASCULARIZATION AFTER ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY VISUALIZED ON OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To describe the qualitative and quantitative changes in choroidal neovascularization (CNV) flow pattern after anti-vascular endothelial growth factor therapy, by optical coherence tomography angiography (OCTA). METHODS: Consecutive patients with neovascular age-related macular degeneration underwent multimodal imaging, including OCTA at initial examination and at last visit. High-flow networks in the choriocapillaris segmentation of OCTA were qualitatively and quantitatively analyzed at baseline and at follow-up, to characterize vascular flow changes after anti-vascular endothelial growth factor treatment and to correlate these changes with final exudation signs on spectral domain optical coherence tomography. RESULTS: Seventeen eyes were included. Mean follow-up was of 11.7 ± 3.3 months. Baseline images showed six medusa pattern (35.3%), four seafan pattern (23.5%), and seven indistinct network patterns (41.2%). Mean CNV area at baseline was 1.58 ± 1.72 mm. Final OCTA images revealed a decrease in CNV total area of 21.6%. In 6/17 eyes, the baseline neovascular pattern was unchanged; these cases were associated with exudation at the final spectral domain optical coherence tomography examination (P = 0.034) and a decrease in CNV area of 34.1%. Conversely, in 11/17 eyes (64.7%), the initial pattern had changed to a pruned vascular tree pattern, with variable exudative status on spectral domain optical coherence tomography at the final visit and a decrease in total CNV area of 0.07%. CONCLUSION: The vascular flow remodeling induced by recurrent anti-vascular endothelial growth factor treatment can be assessed by OCTA. Optical coherence tomography angiography may help to accurately evaluate treatment response and to recognize patterns usually associated with recurrent exudative activity.

OPTICAL COHERENCE TOMOGRAPHY, FLUORESCEIN ANGIOGRAPHY, AND DIAGNOSIS OF CHOROIDAL NEOVASCULARIZATION IN AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To determine the sensitivity and specificity of different retinal imaging combinations for the diagnosis of choroidal neovascularization (CNV) in age-related macular degeneration. METHODS: Patients aged 50 years or older referred for suspicious recent-onset CNV related to age-related macular degeneration were prospectively included for 6 months. Data recorded included color fundus photographs (CFPs), spectral domain optical coherence tomography (SD-OCT), and fluorescein angiography (FA) images. Five retina specialists randomly interpreted SD-OCT combined with CFP, and then FA combined with CFP. The reference diagnosis of CNV was based on the agreement of two readers in the interpretation of the SD-OCT + FA + CFP combination. RESULTS: One hundred and forty-eight patients (148 eyes) were included. For the diagnosis of CNV, the sensitivity of both SD-OCT + CFP and FA + CFP was of 90.9%. Type 2 CNV was diagnosed in 98% to 100% of cases with SD-OCT + CFP or FA + CFP, whereas Type 1 CNV was diagnosed in 82.9% of cases with SD-OCT + CFP and 81.6% with FA + CFP. CONCLUSION: When used as a first diagnostic test, SD-OCT combined with CFP had sensitivity and specificity similar to those of FA combined with CFP, for the diagnosis of CNV in age-related macular degeneration. This shows the increasingly important role of SD-OCT as a first-line test in the diagnosis of CNV.

A dominant mutation in MAPKAPK3, an actor of p38 signaling pathway, causes a new retinal dystrophy involving Bruch's membrane and retinal pigment epithelium.

Inherited retinal dystrophies are clinically and genetically heterogeneous with significant number of cases remaining genetically unresolved. We studied a large family from the West Indies islands with a peculiar retinal disease, the Martinique crinkled retinal pigment epitheliopathy that begins around the age of 30 with retinal pigment epithelium (RPE) and Bruch's membrane changes resembling a dry desert land and ends with a retinitis pigmentosa. Whole-exome sequencing identified a heterozygous c.518T>C (p.Leu173Pro) mutation in MAPKAPK3 that segregates with the disease in 14 affected and 28 unaffected siblings from three generations. This unknown variant is predicted to be damaging by bioinformatic predictive tools and the mutated protein to be non-functional by crystal structure analysis. MAPKAPK3 is a serine/threonine protein kinase of the p38 signaling pathway that is activated by a variety of stress stimuli and is implicated in cellular responses and gene regulation. In contrast to other tissues, MAPKAPK3 is highly expressed in the RPE, suggesting a crucial role for retinal physiology. Expression of the mutated allele in HEK cells revealed a mislocalization of the protein in the cytoplasm, leading to cytoskeleton alteration and cytodieresis inhibition. In Mapkapk3-/- mice, Bruch's membrane is irregular with both abnormal thickened and thinned portions. In conclusion, we identified the first pathogenic mutation in MAPKAPK3 associated with a retinal disease. These findings shed new lights on Bruch's membrane/RPE pathophysiology and will open studies of this signaling pathway in diseases with RPE and Bruch's membrane alterations, such as age-related macular degeneration.