COMPARISON OF PRIMARY AND SECONDARY FORMS OF MULTIPLE EVANESCENT WHITE DOT SYNDROME.

PURPOSE: The aim of this study was to compare primary versus secondary forms of multiple evanescent white dot syndrome (MEWDS) at T0 (baseline) and T1 (1-4 months after the onset of symptoms). METHODS: A total of 101 eyes in 100 patients were included in a multicentric retrospective study. RESULTS: Secondary MEWDS was defined as MEWDS associated with underlying chorioretinal inflammatory pathologies, mainly multifocal choroiditis and punctuate inner choroidopathy. Patients with secondary MEWDS were older (P = 0.011). The proportion of women (P = 0.8), spherical equivalent (P = 0.3), and best-corrected visual acuity at T0 (P = 0.2) were not significantly different between the two groups. The area of MEWDS lesions on late-phase indocyanine green angiography was significantly smaller in secondary MEWDS (P = 0.001) and less symmetrical with respect to both horizontal (P = 0.003) and vertical (P = 0.004) axis. At T0, neither the clinical (P = 0.5) nor the multimodal imaging (P = 0.2) inflammation scores were significantly different between the groups. At T1, the multimodal imaging inflammation score was higher in secondary MEWDS (P = 0.021). CONCLUSION: In secondary MEWDS, outer retinal lesions are less extensive and located close to preexisting chorioretinal lesions. Mild signs of intraocular inflammation on multimodal imaging are more frequent in secondary MEWDS during recovery. These findings suggest that chorioretinal inflammation may trigger secondary MEWDS.

ASSOCIATION BETWEEN ANATOMICAL AND CLINICAL OUTCOMES OF NEOVASCULAR AGE-RELATED MACULAR DEGENERATION TREATED WITH ANTIVASCULAR ENDOTHELIAL GROWTH FACTOR.

PURPOSE: Assess the relationship between subretinal fluid (SRFL), intraretinal fluid, and visual outcomes of neovascular age-related degeneration in routine clinical practice. METHODS: Treatment-naive eyes enrolled in the Fight Retinal Blindness! registry after January 2017 were identified. Lesion activity was graded at each visit as inactive, active not SRFL only (A-NSRFL only), or active SRFL only (A-SRFL only). Eyes were grouped based on initial activity as follows: 1) initially A-NSRFL only or 2) initially A-SRFL only, and their predominant activity status over 12 months was as follows: 1) mostly inactive, 2) mostly A-NSRFL only, or 3) mostly A-SRFL only. RESULTS: Seven hundred and three eyes were eligible for analysis. Initially A-NSRFL only had a similar adjusted mean 12-month visual acuity change to initially A-SRFL eyes (5.7 vs. 6.9 letters; P = 0.165), but their final visual acuity was worse (62.5 vs. 67.5 letters at 12 months; P = 0.003). The adjusted mean 12-month visual acuity change between the predominant activity groups was significantly different (P = 0.005), with mostly inactive (7.6 letters) and mostly A-SRFL only (7.5 letters) eyes gaining more than mostly A-NSRFL only eyes (3.6 letters). CONCLUSION: Eyes with SRFL only had similar outcomes at 1 year to eyes that were mostly inactive. Intraretinal fluid was associated with worse visual outcomes, highlighting the importance of distinguishing between intraretinal fluid and SRFL when managing neovascular age-related degeneration.

Ten-year outcomes of anti-vascular endothelial growth factor treatment for neovascular age-related macular disease: A single-centre French study.

IMPORTANCE: Long-term data of intravitreal injections of vascular endothelial growth factor (VEGF) inhibitors are lacking. BACKGROUND: This study aims to assess visual and anatomic outcomes of eyes with neovascular age-related macular degeneration (nAMD) after 10 years of anti-VEGF therapy. DESIGN: Retrospective analysis of data from a prospectively designed database. PARTICIPANTS: One hundred and sixteen eyes with nAMD (94 participants) that started anti-VEGF therapy at least 10 years earlier. METHODS: Eyes were tracked by the Fight Retinal Blindness! registry. MAIN OUTCOME MEASURES: Mean change in visual acuity at 10 years vs baseline. Visual acuity was assessed by the number of letters read on a logarithm of the minimum angle of resolution chart. RESULTS: Eyes received a median of 27.5 injections over 10 years. Mean visual acuity was 57.5 letters (SD 17.5) at baseline. It increased slightly at 1 year, then dropped steadily by 18 letters (95% CI: 13.7; 22.3) at 10 years. Overall, 10% of eyes gained ≥10 letters, 64% lost ≥10 letters and 23% remained stable (±5 letters from baseline). Geographic atrophy and subretinal fibrosis were found in 93% and 71%, respectively, after 10 years, both mostly affecting the centre of the fovea. Pre-treated eyes (47.5%) had significantly worse visual acuity than treatment-naïve eyes at baseline and during follow-up and were significantly more likely to have atrophy and fibrosis. CONCLUSIONS AND RELEVANCE: Despite short-term stabilization, long-term visual outcomes of nAMD eyes under anti-VEGF therapy may be poor. Development of atrophy and fibrosis, resulting from the natural progression of the disease, may partly explain this evolution.

Aflibercept Treatment in Polypoidal Choroidal Vasculopathy: Results of a Prospective Study in a Caucasian Population.

INTRODUCTION: Polypoidal choroidal vasculopathy (PCV) is a choroidal pathology characterized by frequent occurrences of subretinal hemorrhages and resistance to monotherapies such as ranibizumab or bevacizumab intravitreal injections (IVT). The purpose of this study is to evaluate both the anatomical and functional efficacy of aflibercept IVT as a monotherapy in PCV in a Caucasian population. METHODS: We conducted a prospective multicenter study in either treatment-naïve patients with PCV or PVC patients who had not been treated with anti-VEGF within the previous 3 months or with photodynamic therapy (PDT) within the previous 6 months. All patients had been treated with 3 initial monthly loading doses of aflibercept followed by a Q8 regimen for 28 weeks in total. All patients underwent a complete ophthalmic examination including the measurement of best-corrected visual acuity (BCVA) before each IVT and after 28 weeks as well as an optical coherent tomography (OCT) of the macula. At baseline and 28 weeks, the polypoidal dilations were analyzed with indocyanine green angiography. RESULTS: Thirty-four eyes of 34 patients were included in this study. All patients were followed for 28 weeks and received 5 aflibercept IVT. The mean baseline BCVA was 55 letters. After 28 weeks, significant +13 letters in BCVA and a regression of exudative signs on OCT in all patients were observed. In 62% of the cases, polyp disappearance was observed on indocyanine green angiography. DISCUSSION: In this study on a Caucasian population, we showed that aflibercept as a monotherapy provided both a significant visual gain and the regression of polypoidal dilations. Aflibercept use in monotherapy may contribute to reduce the hemorrhagic risk and atrophy linked to PDT.

Perfluorinated hydroxamic acids are potent and selective inhibitors of HDAC-like enzymes from Pseudomonas aeruginosa.

A series of perfluorinated SAHA (PFSAHA) was prepared and profiled against a panel of human and bacterial members of the Histone deacetylase (HDAC) family. Some of the active substances show nanomolar inhibitory activity and several hundred fold selectivity for the HDAC like enzyme PA3774 from P. aeruginosa. The extraordinary selectivity against human HDACs results from the distinct oligomeric state of PA3774 which consists of two head-to-head dimers. The binding pocket is defined by the surface of both opposite monomers confining the access of ligands to the active site. In addition, the aromatic cap group of PFSAHA undergoes an edge-to-face aromatic interaction with phenylalanine from the opposite monomer.

Martinique Crinkled Retinal Pigment Epitheliopathy: Clinical Stages and Pathophysiologic Insights.

PURPOSE: To reappraise the autosomal dominant Martinique crinkled retinal pigment epitheliopathy (MCRPE) in light of the knowledge of its associated mutated gene mitogen-activated protein kinase-activated protein kinase 3 (MAPKAPK3), an actor in the p38 mitogen-activated protein kinase pathway. DESIGN: Clinical and molecular study. PARTICIPANTS: A total of 45 patients from 3 generations belonging to a family originating from Martinique with an autosomal dominant MCRPE were examined. METHODS: Best-corrected visual acuity, fundus photographs, and spectral-domain optical coherence tomography (SD OCT) of all clinically affected patients and carriers for the causal mutation were reviewed at the initial visit and 4 years later for 10 of them. Histologic retinal lesions of Mapkapk3(-/-) mice were compared with those of the human disease. MAIN OUTCOME MEASURES: The MCRPE natural history in view of MAPKAPK3 function and Mapkapk3(-/-) mouse retinal lesions. RESULTS: Eighteen patients had the c.518T>C mutation. One heterozygous woman aged 20 years was asymptomatic with normal fundus and SD OCT (stage 0). All c.518T>C heterozygous patients older than 30 years of age had the characteristic dried-out soil fundus pattern (stages 1 and 2). Complications (stage 3) were observed in 7 cases, including polypoidal choroidal vasculopathy (PCV) and macular fibrosis or atrophy. One patient was homozygous and had a form with severe Bruch's membrane (BM) thickening and macular exudation with a dried-out soil pattern in the peripheral retina. The oldest heterozygous patient, who was legally blind, had peripheral nummular pigmentary changes (stage 4). After 4 years, visual acuity was unchanged in 6 of 10 patients. The dried-out soil elementary lesions radically enlarged in patients with a preferential macular extension and confluence. These findings are in line with the progressive thickening of BM noted with age in the mouse model. During follow-up, there was no occurrence of PCV. CONCLUSIONS: MCRPE is an autosomal dominant, fully penetrant retinal dystrophy with a preclinical stage, an onset after the age of 30 years, and a preserved visual acuity until occurrence of macular complications. The natural history of MCRPE is in relation to the role of MAPKAPK3 in BM modeling, vascular endothelial growth factor activity, retinal pigment epithelial responses to aging, and oxidative stress.

Clinical Characteristics and Risk Factors of Extensive Macular Atrophy with Pseudodrusen: The EMAP Case-Control National Clinical Trial.

PURPOSE: To assess the association of clinical and biological factors with extensive macular atrophy with pseudodrusen (EMAP) characterized by bilateral macular atrophy occurring in patients aged 50 to 60 years and a rapid progression to legal blindness within 5 to 10 years. DESIGN: A national matched case-control study. PARTICIPANTS: Participants were recruited in 10 French Departments of Ophthalmology and their associated clinical investigation centers. All 115 patients with EMAP had symptoms before the age of 55 years due to bilateral extensive macular atrophy with a larger vertical axis and diffuse pseudodrusen. Three controls without age-related macular degeneration (AMD) or retinal disease at fundus examination were matched for each patient with EMAP by gender, age, and geographic area (in total 415). METHODS: Subjects and controls underwent an eye examination including color, red-free autofluorescent fundus photographs and spectral-domain optical coherence tomography with macular analysis. The interviews collected demographic, lifestyle, family and personal medical history, medications, and biological data. Associations of risk factors were estimated using conditional logistic regression. MAIN OUTCOME MEASURES: Extensive macular atrophy with pseudodrusen status (cases vs. controls). RESULTS: Extensive macular atrophy with pseudodrusen most frequently affected women (70 women, 45 men). After multivariate adjustment, family history of glaucoma or AMD was strongly associated with EMAP (odds ratio [OR], 2.3, P = 0.008 and OR, 1.5, P = 0.01, respectively). No association was found with cardiac diseases or their risk factors. Mild and moderate kidney disease and higher neutrophil rate were associated with a reduced risk of EMAP (OR, 0.58, P = 0.04; OR, 0.34, P = 0.01; and OR, 0.59, P = 0.003, respectively). On the contrary, eosinophilia (OR, 1.6; P = 0.0002), lymphocytosis (OR, 1.84; P = 0.0002), increased erythrocyte sedimentation rate (OR, 6.5; P = 0.0005), decreased CH50 (P = 0.001), and high plasma C3 level (P = 0.023) were significantly associated with a higher risk of EMAP. CONCLUSIONS: This study documents an association between EMAP and family history of AMD and glaucoma, a clear female predominance, and a systemic inflammatory profile. The reduced CH50 and increased C3 plasma values could reflect a more severe complement pathway dysfunction than in AMD, leading to early pseudodrusen and rapid development of geographic atrophy. There is no association of EMAP with AMD cardiac diseases or cardiac risks, including cigarette smoking.

"En face" optical coherence tomography imaging in type 2 idiopathic macular telangiectasia.

PURPOSE: To comprehensively evaluate the retinal and choroidal changes in eyes with Type 2 idiopathic macular telangiectasia using "en face" and B-scan spectral domain optical coherence tomography (OCT), and to compare their respective contributions to this evaluation. METHODS: Eyes with a diagnosis of proliferative or nonproliferative Type 2 macular telangiectasia were prospectively studied. All patients underwent an extensive ophthalmologic examination including biomicroscopic fundus examination, color photography, fundus autofluorescence, fluorescein angiography, B-scan and en face spectral domain OCT. RESULTS: Twenty eyes of 10 patients were included in this study. En face OCT C-scans and conventional B-scans were both able to show inner crystalline deposits (15%), retinal capillary anomalies (100%), intraretinal cysts (80%), hyperreflective spots in the outer nuclear layer (100%) and external limiting membrane (80%), hyperplastic pigment plaques (30%), intraretinal neovascularization (20%), photoreceptor loss (100%), and choroidal cavitations (30%). En face OCT C-scans provided more information than B-scans on intraretinal neovascularization, photoreceptor loss, and choroidal cavitations. Also, en face OCT C-scans provided better visualization of the retinal vessels and telangiectasia than fluorescein angiography. CONCLUSION: En face OCT is a noninvasive and reproducible technique that helps to better assess and follow up retinal and choroidal processes in Type 2 macular telangiectasia.

Effect of baseline fluid localization on visual acuity and prognosis in type 1 macular neovascularization treated with anti-VEGF.

PURPOSE: To assess the prognostic value of subretinal (SRF) and intraretinal fluid (IRF) localizations in type 1 macular neovascularization (MNV) due to age-related macular degeneration (AMD). SUBJECTS: Eyes were prospectively treated with anti-vascular epithelial growth factor (anti-VEGF) intravitreal injections (IVT) according to a Pro-Re-Nata (PRN) or Treat and Extend (TAE) regimen during 24 months. A total of 211 eyes with treatment-naïve type 1 MNV secondary to AMD were consecutively included. Eyes were divided between 2 groups according to the fluid localization: presence of SRF alone (SRF group), or presence of IRF associated or not with SRF (IRF ± SRF group). RESULTS: At baseline the mean BCVA was 66.2 letters. SRF was present in 94.8% of eyes, IRF in 30.8%, and both in 25.6%. Data were available for 201 eyes at 12 months, and 157 eyes at 24 months. The presence of IRF at baseline was associated with lower baseline BCVA and significantly lower BCVA at 12 months (p < 0.001) and 24 months (p < 0.001). Eyes with SRF alone displayed better visual outcomes (BCVA at month 12, SRF = 74.3 letters, IRF ± SRF = 56.9 letters). In the presence of baseline IRF, fibrosis (p = 0.03) and atrophy (p < 0.001) were more frequently found at 24 months. In a multivariate model, the presence of baseline IRF was significantly associated with lower BCVA at month 12 but not at month 24. CONCLUSION: In type 1 MNV, the presence of baseline IRF was associated with worse visual outcomes compared to SRF alone, and more frequent atrophy and fibrosis.

Subretinal fibrosis occurrence according to macular neovascularisation subtypes in neovascular age-related macular degeneration.

PURPOSE: To assess subretinal fibrosis (SF) occurrence in neovascular age-related macular degeneration (nAMD), according to macular neovascularisation (MNV) subtypes. METHODS: A Retrospective national multi centre cohort study included eyes with naive nAMD. Main outcome measures were, according to MNV subtypes, cumulative incidence for SF, risk factors, and best corrected visual acuity (BCVA) for 36 months. RESULTS: Four hundred and twenty eyes were included. Cumulative incidence of SF was 34.3% at 1 year, 39.0% at 2 years and 50.6% at 3 years. In multivariable analysis, Type 2 and mixed type 1 and 2 MNV were associated (p < 0.001) with a more frequent and rapid development of SF (respectively 85.5% and 81.0% at 1 year, then 95.8% and 93.1% at 3 years) than Types 1 and 3 (respectively 11.3% and 3.6% at 1 year, then 22.9% and 12.7% at 3 years). In Type 2 and mixed type 1 and 2 MNV combined, at baseline a worse BCVA (p = 0.02) and a higher maximal subretinal hyperreflective material (SHRM) thickness (p = 0.005) were associated with SF development at 3 years. In Type 1 MNV, the presence at baseline of intraretinal fluid (IRF) (p = 0.007) or SHRM (p < 0.001) and a higher percentage of visits with IRF (p < 0.001) or with SHRM (p < 0.001) were associated with SF occurrence. For Type 3 MNV, only a higher percentage of visits with SHRM (p = 0.001) was associated with SF. Including all MNV subtypes, eyes with a worse BCVA at baseline were associated with SF development (p < 0.001). Conversely, presence of SF at 3 years was associated with a worse baseline BCVA (p < 0.001). CONCLUSION: Occurrence of SF differs when considering apart MNV subtypes.