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.

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."

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.

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.

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.

Ranibizumab for choroidal neovascularization secondary to pseudoxanthoma elasticum: 4-year results from the PIXEL study in France.

PURPOSE: To evaluate the long-term effectiveness and safety of ranibizumab 0.5 mg in patients with choroidal neovascularization (CNV) secondary to pseudoxanthoma elasticum (PXE) in a real-world setting. METHODS: A descriptive, observational, multicenter study in a retrospective and prospective cohort was conducted in France that included patients who had received at least one injection of ranibizumab 0.5 mg during the period October 2011 to October 2014, for CNV secondary to PXE. Eligible patients were identified by review of medical records or during routine consultations. The main objectives were to describe patient characteristics, assess changes in best-corrected visual acuity [VA, Early Treatment Diabetic Retinopathy Study (ETDRS) letters] over time, the number and reasons for ranibizumab treatment and overall safety. RESULTS: Of the 72 enrolled patients (98 eyes) from 23 centers, 39 (54.2%) were male and mean [±standard deviation (SD)] age was 59.6 (±8.3) years. The mean VA was 64.6 letters at the first ranibizumab injection, which was maintained at the 1-year follow-up (64.7 letters). Thereafter, the mean VA was stable until the 4-year follow-up. At 4 years, the proportion of eyes with VA gain of ≥15 letters was 3/19 (15.8%) and stable VA (change between -15 and +15 letters) was 10/19 (52.6%). Mean (±SD) annual number of ranibizumab injections was 4.1 (±4.0), lower in the second versus first year. The most common reason for ranibizumab treatment was progression of neovascular activity (42.9%). No deaths or new safety findings were reported. CONCLUSIONS: In patients with CNV secondary to PXE, ranibizumab 0.5 mg resulted in stable VA over 4 years with a limited number of injections. Safety findings were consistent with the established safety profile of ranibizumab.

NEOVASCULARIZATION SECONDARY TO HIGH MYOPIA IMAGED BY OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To describe the optical coherence tomography angiography (OCTA) characteristics of active myopic choroidal neovascularization (CNV) and to compare its sensitivity versus fluorescein angiography and spectral-domain optical coherence tomography. METHODS: Consecutive highly myopic patients complicated with active myopic CNV were prospectively included. The OCTA features were analyzed and correlated with the findings of conventional imaging (spectral-domain optical coherence tomography and fluorescein angiography). RESULTS: Twenty eyes of 19 patients (mean age: 59.6 ± 12.1 years, mean spherical equivalent: -13.5 ± 3.6 diopters) presenting with both treatment-naive CNV and recurrent CNV were included in the analysis. The OCTA showed a 90% sensitivity for myopic CNV detection in 18 of 20 eyes, revealing a high-flow neovascular network accurately visible using a 30-µm manual segmentation underneath Bruch membrane. Mean selected area of myopic CNV on OCTA images was 0.34 ± 0.45 mm, whereas the mean vessel area was 0.22 ± 0.27 mm. Two neovascular phenotypes prevailed in our series: disorganized vascular loops and organized interlacing patterns. CONCLUSION: The OCTA seems to be a valuable tool in detecting myopic CNV with a high sensitivity. However, its specificity needs to be investigated in further studies.

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.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FEATURES OF SUBRETINAL FIBROSIS IN AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To report the imaging features of subretinal fibrosis secondary to exudative age-related macular degeneration (AMD) on optical coherence tomography angiography. METHODS: All consecutive patients diagnosed with subretinal fibrosis complicating exudative AMD were imaged by color retinal photographs or multicolor imaging, fluorescein angiography, spectral domain optical coherence tomography, and optical coherence tomography angiography. Eyes with active exudative features observed during the last 6 months were compared with those without any sign of exudation >6 months. RESULTS: Forty-nine eyes of 47 consecutive patients were included. A blood flow inside the fibrotic scar could be detected in 46 of 49 cases (93.8%). Three patterns of vascular networks could be distinguished, that were described as pruned vascular tree (26 of 49 eyes; 53.1%), tangled network (14 of 49; 28.6%), and/or vascular loop (25 of 49; 51.0%). Furthermore, 2 types of hyporeflective structures, large flow void, and/or dark halo were observed in 63% and in 65% of eyes, respectively. The observed patterns did not differ between eyes with active or inactive lesions. CONCLUSION: Optical coherence tomography angiography of subretinal fibrosis showed almost constantly a perfused, abnormal vascular network and collateral architectural changes in the outer retina and the choriocapillaris layer. These features were associated with both active and inactive fibrotic choroidal neovessels.

Risk factors for exudative age-related macular degeneration in a large French case-control study.

PURPOSE: The purpose of the CAP (Creteil AMD PHRC-funded) Study was to analyze risk factors of exudative age-related macular degeneration (AMD) in a large French case-control population. PATIENTS AND METHODS: One thousand and twenty-four patients with exudative AMD and 275 controls were recruited. Information about lifestyle, medical history, and dietary intake were collected. Associations of risk factors were estimated using logistic regression. RESULTS: After multivariate adjustment, CFH Y402H and ARMS2 A69S polymorphisms were associated with very high risk for exudative AMD (OR = 6.21 and OR = 11.7, respectively, p < 0.0001). Risk for exudative AMD was increased in current smokers (OR = 3.79, p = 0.0003) and former smokers having quitted since less than 20 years ago (OR = 2.30, p = 0.002), but not in former smokers having quitted since 20 years or more ago (OR = 0.81, p = 0.43). Heavy smokers (at least 25 pack-years) were particularly at risk (OR = 3.61, p < 0.0001). Use of cooking oils rich in omega 3 fatty acids was significantly associated with a reduced risk of exudative AMD (OR = 0.55, 95 % CI: 0.36-0.84, p = 0.006), as well as a high consumption of fruits (OR = 0.60, 95 % CI: 0.37-0.98, p = 0.04), but not the consumption of fish, vegetables or oils rich in omega 6. High waist circumference was associated with increased risk for exudative AMD (OR = 2.53, p < 0.0001), but not hypercholesterolemia, hypertension, or body mass index. CONCLUSIONS: The CAP Study confirms major genetic risk factors for exudative AMD. It further documents the high risk in heavy smokers and the long persistence of risk after smoking cessation, and the associations with waist circumference and fruit consumption. Furthermore, we observed an inverse correlation between AMD and cooking oils harboring a beneficial omega-3 fatty acid profile.

Bimonthly ranibizumab for neovascular age-related macular degeneration.

BACKGROUND/PURPOSE: Recently, aflibercept was proposed with a protocol of a bimonthly fixed regimen. Our purpose was to evaluate the results of this regimen in patients treated with ranibizumab. METHOD: We conducted a retrospective analysis of consecutive patients with naïve neovascular age-related macular degeneration treated with a bimonthly fixed regimen of intravitreal injections of ranibizumab after 3 monthly injections. Examination was performed every 4 weeks for 52 weeks, with the possibility of unscheduled rescue injections of ranibizumab. RESULTS: A total of 27 patients, 24 women and 3 men, aged from 68 to 90 years (mean: 81.2) were analyzed; 25 eyes (92.5%) lost <15 letters. Mean BCVA rose from 58.3 (range ± 12.9) to 66.7 (range ± 14.3) letters. The mean visual gain was 8.40 (range ± 13.2) letters; 11 patients (40.7%) gained ≥ 15 letters. The mean number of injections of ranibizumab was 8.77. CONCLUSION: Bimonthly intravitreal ranibizumab achieved satisfactory visual results. However, patients who required additional injections did not experience significant visual gain.

Navigated Focal Laser of Macular Telangiectasia Type I (Adult-Onset Coats' Disease).

We aimed to evaluate the anatomical and functional outcome of selective photocoagulation of idiopathic macular telangiectasia type 1 by navigated focal laser (Navilas, OD-OS GmBH). Consecutive patients with idiopathic macular telangiectasia type 1 were included in the analysis. All patients were treated with navigated focal laser, planned on multimodal imaging. Seven eyes of seven patients were retrospectively analyzed. Navigated laser photocoagulation of idiopathic macular telangiectasia type 1 successfully occluded the microaneurysms, inducing regression of macular edema and exudation, significative improvement in best-corrected visual acuity at 3 (P = 0.035) and 6 months (P = 0.034) and a decrease in central macular thickness at 3 (P = 0.01) and 6 months (P = 0.01). Patients with idiopathic macular telangiectasia type 1 are ideal candidates for navigated laser treatment. Navigated focal treatment has been shown to be effective and safe in occluding aneurysmal dilations without any side effects. [Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.].

Genetic association study of mitochondrial polymorphisms in neovascular age-related macular degeneration.

PURPOSE: Age-related macular degeneration (AMD) is a multifactorial disease involving genetic and environmental factors. Most of the genetic factors identified so far involve the nuclear genome. Recently, two studies in North America and Australia reported an association between advanced AMD and the mitochondrial T2 haplogroup. Our purpose was to assess this association in a large French population. METHODS: This case control study included 1,224 patients with neovascular AMD and 559 controls with normal fundus. Mitochondrial DNA polymorphisms at and around nucleotides 4917, 11,812, and 14,233 were determined using PCR amplification and direct sequencing of mitochondrial DNA. RESULTS: No association was found between the mitochondrial T2 haplogroup and neovascular AMD in the French population: 94/1,152 patients with neovascular AMD had the T2 haplogroup (8.2%) versus 34/482 controls (7.1%; odds ratio=0.9 [0.5-1.5], p=0.66). CONCLUSIONS: An association between AMD and the T2 haplogroup, previously described in North American and Australian populations, was not confirmed in a large French population.

OCULAR DECOMPRESSION RETINOPATHY WITH BRANCH RETINAL VEIN OCCLUSION MTHF-R GENETIC MUTATION.

PURPOSE: An atypical case of a sectorial decompression retinopathy with branch retinal vein occlusion following trabeculectomy was reported and was diagnosed with optical coherence tomography angiography for which systemic genetic assessment revealed a MTHF-R mutation. METHOD: Single case report. RESULTS: A 68-year-old woman diagnosed with an uncontrolled bilateral creeping angle glaucoma went through an uncomplicated trabeculectomy in both eyes. Best-corrected visual acuity was 20/20. Intraocular pressure changed from 28 mmHg preoperatively to 5 mmHG postoperatively in the right eye. On the first postoperative day, best-corrected visual acuity was 20/32 with intraocular pressure measured to 5 mmHg. Fundus examination revealed sectorial temporal hemorrhages with tortuous temporal superior retinal vein arcade and choroidal folds. Fluorescein angiography evidenced a slight delay in venous filling along the supratemporal arcade. Three months later, optical coherence tomography angiography showed macular capillary loops in the superotemporal area of the retina. This sectorial decompression retinopathy was evocative of a branch retinal vein occlusion. At 6 months, best-corrected visual acuity returned to 20/20, with full regression of the hemorrhages. Systemic workup was normal, but genetic assessment revealed a MTHF-R mutation. CONCLUSION: Retinal vein occlusion can be considered as a feature of ocular decompression retinopathy. The present case is the first case to associate branch retinal vein occlusion secondary to ocular decompression retinopathy to a MTHF-R mutation.

Subretinal autofluorescent deposits: A review and proposal for clinical classification.

Subretinal autofluorescent deposits (SADs) may be found in the posterior pole, associated with very various conditions. These disorders usually present a typical pattern of autofluorescent lesions seen on short-wavelength fundus autofluorescence. We describe SADs according to their putative pathophysiological origin and also according to their clinical pattern, i.e., number, shape, and usual location. Five main putative pathophysiological origins of SADs were identified in disorders associated with an intrinsic impairment of phagocytosis and protein transportation, with excess of retinal pigment epithelium phagocytic capacity, with direct or indirect retinal pigment epithelium injury, and/or disorders associated with long-standing serous retinal detachment with mechanical separation between the retinal pigment epithelium and the photoreceptor outer segments. Clinically, however, they could be classified into eight subclasses of SADs, as observed on fundus autofluorescence as follows: single vitelliform macular lesion, multiple roundish or vitelliform lesions, multiple peripapillary lesions, flecked lesions, leopard-spot lesions, macular patterned lesions, patterned lesions located in the same area as the causal disorder, or nonpatterned lesions. Thus, if multimodal imaging may be required to diagnose the cause of SADs, the proposed classification based on noninvasive, widely available short-wavelength fundus autofluorescence could guide clinicians in making their diagnosis decision tree before considering the use of more invasive tools.