Stargardt disease-associated in-frame ABCA4 exon 17 skipping results in significant ABCA4 function.

BACKGROUND: ABCA4, the gene implicated in Stargardt disease (STGD1), contains 50 exons, of which 17 contain multiples of three nucleotides. The impact of in-frame exon skipping is yet to be determined. Antisense oligonucleotides (AONs) have been investigated in Usher syndrome-associated genes to induce skipping of in-frame exons carrying severe variants and mitigate their disease-linked effect. Upon the identification of a STGD1 proband carrying a novel exon 17 canonical splice site variant, the activity of ABCA4 lacking 22 amino acids encoded by exon 17 was examined, followed by design of AONs able to induce exon 17 skipping. METHODS: A STGD1 proband was compound heterozygous for the splice variant c.2653+1G>A, that was predicted to result in in-frame skipping of exon 17, and a null variant [c.735T>G, p.(Tyr245*)]. Clinical characteristics of this proband were studied using multi-modal imaging and complete ophthalmological examination. The aberrant splicing of c.2653+1G>A was investigated in vitro in HEK293T cells with wild-type and mutant midigenes. The residual activity of the mutant ABCA4 protein lacking Asp864-Gly885 encoded by exon 17 was analyzed with all-trans-retinal-activated ATPase activity assay, along with its subcellular localization. To induce exon 17 skipping, the effect of 40 AONs was examined in vitro in WT WERI-Rb-1 cells and 3D human retinal organoids. RESULTS: Late onset STGD1 in the proband suggests that c.2653+1G>A does not have a fully deleterious effect. The in vitro splice assay confirmed that this variant leads to ABCA4 transcripts without exon 17. ABCA4 Asp864_Gly863del was stable and retained 58% all-trans-retinal-activated ATPase activity compared to WT ABCA4. This sequence is located in an unstructured linker region between transmembrane domain 6 and nucleotide-binding domain-1 of ABCA4. AONs were designed to possibly reduce pathogenicity of severe variants harbored in exon 17. The best AON achieved 59% of exon 17 skipping in retinal organoids. CONCLUSIONS: Exon 17 deletion in ABCA4 does not result in the absence of protein activity and does not cause a severe STGD1 phenotype when in trans with a null allele. By applying AONs, the effect of severe variants in exon 17 can potentially be ameliorated by exon skipping, thus generating partial ABCA4 activity in STGD1 patients.

Prognostic factors of idiopathic epiretinal membrane surgery and evolution of alterations of the central cone bouquet.

PURPOSE: To describe the structural changes observed postoperatively in epiretinal membranes (ERM), in particular the alterations in the central cone bouquet (CB), and to identify prognostic factors that might predict postoperative outcome. METHODS: We included 125 eyes of 117 patients who underwent idiopathic ERM removal with at least a 6-month follow-up. For each patient, spectral-domain optical coherence tomography (SD-OCT) was performed and best-corrected visual acuity (BCVA) was measured, before and after surgery. RESULTS: Before surgery, 44 eyes (35.2%) presented CB alterations: 65.9% a cotton ball sign, 15.9% a foveolar detachment and 18.2% a pseudovitelliform lesion. Median BCVA increased from 20/63 to 20/32 post-operatively (p = .001) with a mean follow-up of 17 months. The disappearance of CB alterations after surgery was observed in 97.7% of eyes. In stage 3 and 4 ERM, ectopic inner foveal layers persisted in 76.7% of eyes after surgery. Postoperative BCVA was correlated with change in central macular thickness and initial BCVA and was not correlated with the presence of preoperative CB alteration, the initial stage of ERM, the presence of postoperative dissociated optical nerve fiber layer, and the disappearance of ectopic inner fiber layers. The combination of cataract surgery and capsulotomy did not seem to change visual outcome and seemed to accelerate visual recovery. Incidentally, general anesthesia was correlated with final BCVA. CONCLUSION: ERM surgery allowed a significant gain in BCVA and the disappearance of CB alterations in the great majority of cases. CB alteration did not show to be associated with poor visual prognosis.

RESPONSE OF CHOROIDAL ABNORMALITIES TO PHOTODYNAMIC THERAPY VERSUS MICROPULSE LASER IN CHRONIC CENTRAL SEROUS CHORIORETINOPATHY: Place Trial Report No. 4.

PURPOSE: To compare the effects of half-dose photodynamic therapy (PDT) and high-density subthreshold micropulse laser on choroidal dysfunction evaluated by degree and extent of hyperfluorescence on indocyanine green angiography (ICGA) in chronic central serous chorioretinopathy. METHODS: Data from the multicenter, randomized, controlled PLACE trial were used in this study. Hyperfluorescent and hypofluorescent areas on ICGA, their association with subretinal fluid and visual function were assessed. RESULTS: In total, 146 patients were included (72 in the PDT and 74 in the high-density subthreshold micropulse laser treatment arm). A significantly greater decrease in the size of hyperfluorescent areas on ICGA at first visit after treatment was seen after PDT compared with high-density subthreshold micropulse laser (mean, -1.41 ± 2.40 mm2 vs. -0.04 ± 0.73 mm2, respectively; P < 0.001). A reduction in the degree of hyperfluorescence on ICGA decreased the odds of having persistent subretinal fluid on optical coherence tomography at first visit after treatment (B = 0.295; P = 0.019). There were no significant differences in best-corrected visual acuity and retinal sensitivity between the subgroup with novel hypofluorescence (n = 20, 28%) on ICGA at first visit post PDT, compared with the subgroup without novel hypofluorescence on ICGA after PDT. CONCLUSION: Choroidal abnormalities in chronic central serous chorioretinopathy can be effectively treated by ICGA-guided half-dose PDT but not with high-density subthreshold micropulse laser application.

GENETICS OF LARGE PIGMENT EPITHELIAL DETACHMENTS IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: We hypothesized that severe forms of neovascular age-related macular degeneration (AMD) such as large pigment epithelial detachments poorly responding to anti-vascular endothelial growth factor therapy might present a distinct genotype compared with overall series of neovascular AMD. METHODS: This is a multicenter genetic association study. Sixty-eight patients presenting pigment epithelial detachments resistant to ranibizumab (issued from ARI2 study, register number NCT02157077 on clinicaltrials.gov) were compared with two series of patients derived from previously published clinical studies, presenting neovascular AMD (NAT2 study n = 300 and PHRC study n = 1,127), and with healthy controls (n = 441). The phenotype of neovascular AMD groups was based on visual acuity measurement, fundus examination, spectral-domain optical coherence tomography, and angiographic data. All samples were genotyped for three single-nucleotide polymorphisms: CFH (rs1061170), ARMS2 (rs10490924), and C3 (rs2230199). Significant difference in allele frequency between participants with neovascular AMD and control was the main outcome measurement. RESULTS: The GG genotype of the C3 rs2230199 was significantly more frequent in the ARI2 group (55.9%) than the PHRC group (6.0%, P < 0.0001; odds ratio = 24.0 [95% confidence interval 10.4-55.0]) and the NAT2 group (5.1%, P < 0.0001; odds ratio = 16.1 [95% confidence interval 5.0-51.9]). The repartition of patients carrying a T allele of the ARMS2 (rs10490924) or patients carrying a C allele of the CFH (rs1061170) was similar in the ARI2 group when compared with the NAT2 and PHRC groups. CONCLUSION: In our series, the genotype GG of C3 rs2230199 was more significantly associated with the phenotype of large vascularized pigment epithelial detachment poorly responding to anti-vascular endothelial growth factor therapy than in global AMD series.

Patient characteristics of untreated chronic central serous chorioretinopathy patients with focal versus diffuse leakage.

PURPOSE: To describe the characteristics and potential differences between focal and diffuse phenotypes of untreated chronic central serous chorioretinopathy (cCSC). METHODS: For this study, patients were divided in two groups. Focal leakage was defined as 1 "hot spot" of leakage, whereas diffuse leakage was defined as either > 1 hot spot or a larger area of widespread leakage on FA. Clinical characteristics were assessed at presentation. After Bonferroni correction, P values < 0.00125 were deemed statistically significant. RESULTS: The focal leakage group included 68 eyes (53 males), and the diffuse leakage group included 105 eyes (88 males). Mean best-corrected visual acuity (BCVA) was 77.1 ± 8.1 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters in the focal group and 76.0 ± 9.6 ETDRS letters in the diffuse group (p = 0.440). In the focal group, mean age was 46.9 ± 8.8 years, whereas this was 49.7 ± 8.3 years in the diffuse group (p = 0.033). Mean central foveal thickness was 107.1 ± 21.3 µm in the focal group and 106.2 ± 27.3 µm in the diffuse group (p = 0.818). Mean choroidal thickness was 407.5 ± 114.8 µm in the focal group and 419.1 ± 113.9 µm in the diffuse group (p = 0.578). In the focal group, subretinal fluid was present in the fellow eye in 16% of the patients, as compared to 29% in the diffuse group (p = 0.067). CONCLUSIONS: In untreated cCSC patients with focal or diffuse leakage on FA, no marked differences in clinical characteristics were found. Extensive choroidal abnormalities may be present in both groups, which are presumed to lie at the basis of the development of cCSC.

Half-Dose Photodynamic Therapy versus High-Density Subthreshold Micropulse Laser Treatment in Patients with Chronic Central Serous Chorioretinopathy: The PLACE Trial.

PURPOSE: To compare the anatomic and functional efficacy and safety of half-dose photodynamic therapy (PDT) versus high-density subthreshold micropulse laser (HSML) treatment in patients with chronic central serous chorioretinopathy (cCSC). DESIGN: Open-label, multicenter, randomized controlled clinical trial. PARTICIPANTS: Patients with cCSC whose disease had to be confirmed by both clinical characteristics and findings on multimodal imaging. METHODS: Eligible patients were randomized in a 1:1 allocation ratio. Treatment was evaluated during a follow-up visit, and the same treatment was repeated in patients who still demonstrated subretinal fluid (SRF). MAIN OUTCOME MEASURES: The primary end point was the complete disappearance of SRF at the first evaluation visit at 6 to 8 weeks after treatment. As a secondary outcome measure, we assessed this anatomic result at the final evaluation visit at 7 to 8 months after treatment. Other secondary outcomes covered functional improvement and included change in best-corrected visual acuity (BCVA; measured in Early Treatment Diabetic Retinopathy Study [ETDRS] letters), retinal sensitivity (measured using microperimetry), and vision-related quality of life using a validated questionnaire. RESULTS: Between November 2013 and September 2016, 179 patients were included: 89 patients were assigned randomly to half-dose PDT, and 90 were assigned randomly to HSML treatment. At their first evaluation visit, SRF had resolved in 51.2% and 13.8% of patients, respectively (P < 0.001). At their final evaluation visit, a significantly higher percentage of PDT-treated patients demonstrated no SRF (67.2% vs. 28.8%; P < 0.001). Moreover, at the first evaluation visit, the PDT-treated patients showed a significantly higher increase in BCVA (+4.60±6.62 ETDRS letters vs. +1.39±8.99 ETDRS letters; P = 0.011), and a significantly higher increase in retinal sensitivity on microperimetry (+2.01±3.04 dB vs. +0.92±3.65 dB; P = 0.046); however, the improvement in vision-related quality of life was similar (score of +2.87±8.35 vs. +2.56±7.36, respectively; P = 0.800). CONCLUSIONS: Half-dose PDT is superior to HSML for treating cCSC, leading to a significantly higher proportion of patients with complete resolution of SRF and functional improvement.

WRINKLED VASCULARIZED RETINAL PIGMENT EPITHELIUM DETACHMENT PROGNOSIS AFTER INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY.

BACKGROUND/PURPOSE: Neovascular age-related macular degeneration (nAMD) is frequently associated with vascularized pigment epithelial detachment (v-PED). We observed a peculiar characteristic of v-PED characterized by small lacy folds of the retinal pigment epithelium, appearing as a wrinkled PED (w-PED) on spectral domain optical coherence tomography (SD-OCT). Our purpose was to describe the visual prognosis and number of intravitreal injections in w-PED compared with non-w-PED. METHODS: In this retrospective, case-control series, we reviewed retrospectively medical records of 52 eyes of 51 patients who were consecutively included between November 1 and 30, 2015 with a previous minimum 3-year follow-up. Inclusion criteria were: neovascular age-related macular degeneration, affected with w-PED. Baseline characteristics, best-corrected visual acuity (BVCA), number of intravitreal anti-vascular endothelial growth factor injections (anti-VEGF IVT) and maximal recurrence-free interval, that is, without intravitreal anti-vascular endothelial growth factor injection, were analyzed. A w-PED was defined as a v-PED ≥200 µm in height on SD-OCT imaging, presenting with at least 4 small lacy folds on the surface of the retinal pigment epithelium. Patients were compared with a control group, that is, patients harboring PED without wrinkle shape (non-w-PED). All patients had been treated by intravitreal anti-vascular endothelial growth factor injection of either ranibizumab (IVR) or aflibercept (IVA) using a pro re nata (PRN) protocol after three initial monthly treatments, with a minimum of follow-up of 3 years. RESULTS: Two groups of patients were compared, w-PED (29 eyes, from 29 patients), and non-w-PED (23 eyes from 22 patients). In the w-PED group, mean BCVA evolved from 0.28 (±0.18) log MAR (20/40, range 20/25-20/63) at baseline, to 0.29 (±0.21) log MAR (20/40, range 20/25-20/63) at 1 year (P = 0.41), 0.34 (±0.26) log MAR (20/40, range 20/25-20/80) at 2 years (P = 0.49), 0.35 (±0.28) log MAR (20/40, range 20/25-20/80) at 3 years (P = 0.54). In the non-w-PED group, mean BCVA was 0.40 (±0.28) log MAR (20/50, range 20/25-20/100) at baseline and decreased to 0.48 (±0.46) log MAR (20/63, range 20/20-20/160) at 1 year (P = 0.19), 0.48 (±0.35) log MAR (20/63, range 20/25-20/125) at 2 years (P = 0.02), 0.60 (±0.38) log MAR (20/80, range 20/32-20/200) at 3 years (P = 0.002). In the w-PED group, the mean maximal documented recurrence-free interval was 7.87 (±2.94) months at Year 1, 13.5 (±7.52) at Year 2 and 14.78 (±10.70) at Year 3, versus 4.59 (±2.95) months at Year 1, 7.83 (±6.62) at Year 2, 8.57 (±11.18) at Year 3 in the non-w-PED group (P = 0.0004; 0.0101; 0.0168 respectively at Years 1, 2 and 3). DISCUSSION: The evolution of v-PED after intravitreal anti-vascular endothelial growth factor injection is still difficult to predict despite intense clinical research in this topic. In our study, we noticed that w-PED might be a phenotypic prognosis factor for better visual acuity and longer maximal recurrence-free interval.

AFLIBERCEPT AFTER RANIBIZUMAB INTRAVITREAL INJECTIONS IN EXUDATIVE AGE-RELATED MACULAR DEGENERATION: The ARI2 Study.

PURPOSE: To analyze the efficacy of aflibercept switch treatment for regression of pigment epithelial detachment (PED) in patients previously treated with ranibizumab. METHODS: Multicenter, prospective, nonrandomized clinical trial. One eye of patients presenting neovascular age-related macular degeneration with PED of more than 250 µm in height, with persistent fluid, was included. Patients had to have received at least six ranibizumab intravitreal injections during the 12 months before enrollment. Patients were switched from ranibizumab pro re nata to aflibercept (fixed regimen, 3 monthly intravitreal injections, and then Q6). Main outcome measure was change in PED height from baseline to Week 12 after switch. Secondary outcomes were best-corrected visual acuity and PED volume changes. RESULTS: Eighty four patients were included. Mean delay between last ranibizumab intravitreal injection and switch was 44.7 days. Mean maximal PED height at baseline visit was 347 µm (±109) and reduced to a mean of 266 µm (±114) at Week 12 (P < 0.001) and 288.2 µm at Week 32 (P < 0.001). Mean PED volume was reduced from 1.3 mm to 0.98 mm at Week 12 (P < 0.001). Best-corrected visual acuity improved by 3.3 Early Treatment Diabetic Retinopathy Study letters at Week 32 (P = 0.003). CONCLUSION: Aflibercept switch therapy seems to be effective on large PED in patients previously treated with pro re nata ranibizumab.

Sensitivity and specificity of optical coherence tomography angiography (OCT-A) for detection of choroidal neovascularization in real-life practice and varying retinal expertise level.

PURPOSE: To evaluate the diagnostic accuracy of OCT angiography (OCT-A) detecting or predicting choroidal neovascularization (CNV), by ophthalmologists of disparate degrees of skills in retinal diseases, using spectral domain optical coherence tomography (SD-OCT) and fluorescein angiography (FA) as a standard reference. METHODS: Retrospective observational case series. Patient presenting maculopathy and complete imaging were included. FA, SD-OCT, OCT-A and FA coupled to SD-OCT images were graded independently for presence or absence of CNV by ophthalmologists with varying expertise levels. RESULTS: Overall sensitivity of OCT-A was 85.62% (95% CI 79.04-90.76%) and specificity was 81.51% (95% CI 73.36-88.03). Sensitivity of FA was 74.51% (95% CI 66.84-81.20), and specificity was 82.35% (95% CI 74.30-88.73). Sensitivity of FA + SD-OCT was 92.72% (95% CI 87.34-96.30), and specificity was 90.91% (95% CI 84.31-95.37). CONCLUSION: OCT-A has good sensitivity and specificity for the detection of CNV in all expertise level groups. OCT-A may soon become a routine tool for CNV diagnosis and follow-up.

Ranibizumab for vascularized pigment epithelial detachment: 1-year anatomic and functional results.

PURPOSE: To assess the anatomical and functional efficacy of ranibizumab on vascularized pigment epithelial detachment (V-PED) secondary to neovascular age-related macular degeneration (nAMD). METHODS: One hundred and nine patients (116 eyes) were retrospectively selected from medical records of 2097 patients who benefited from intravitreal injection between January 2011 and June 2013 in a tertiary-care University-based Department of Ophthalmology. Inclusion criteria were: nAMD, treatment-naive eyes, presence of V-PED higher than 250 µm, intravitreal ranibizumab with a loading phase, followed by a pro-re-nata regimen, and 1-year follow-up. Baseline characteristics and type of choroidal neovascularization (CNV) were analyzed. PED height, central macular thickness (CMT) and best-corrected visual acuity (BCVA, logMAR) were measured at baseline, months 3, 6 and 12. RESULTS: CNV was of type 1 in 91 eyes (78.4 %), type 2 in seven (6 %), type 3 in six (5.2 %), and polypoidal choroidal vasculopathy in 12 (10.3 %). Mean CMT at baseline was 572.1 µm and decreased to 396.6 µm (p < 0.0001) at 12 months. Mean height of PED was 458.2 µm at baseline and 306.8 µm (p < 0.0001) at 12 months. Mean BCVA improved from 0.46 at baseline to 0.39 at 12 months (p = 0.013). CONCLUSIONS: Treatment with ranibizumab improved visual and anatomical outcome in nAMD patients with V-PED.

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.

ADAPTIVE OPTICS IMAGING OF FOVEAL SPARING IN GEOGRAPHIC ATROPHY SECONDARY TO AGE-RELATED MACULAR DEGENERATION.

BACKGROUND: To describe adaptive optics (AO) imaging of foveal sparing in geographic atrophy (GA) secondary to age-related macular degeneration. METHODS: Flood-illumination AO infrared (IR) fundus images were obtained in four consecutive patients with GA using an AO retinal camera (rtx1; Imagine Eyes). Adaptive optics IR images were overlaid with confocal scanning laser ophthalmoscope near-IR autofluorescence images to allow direct correlation of en face AO features with areas of foveal sparing. Adaptive optics appearance of GA and foveal sparing, preservation of functional photoreceptors, and cone densities in areas of foveal sparing were investigated. RESULTS: In 5 eyes of 4 patients (all female; mean age 74.2 ± 11.9 years), a total of 5 images, sized 4° × 4°, of foveal sparing visualized on confocal scanning laser ophthalmoscope near-IR autofluorescence were investigated by AO imaging. En face AO images revealed GA as regions of inhomogeneous hyperreflectivity with irregularly dispersed hyporeflective clumps. By direct comparison with adjacent regions of GA, foveal sparing appeared as well-demarcated areas of reduced reflectivity with less hyporeflective clumps (mean 14.2 vs. 3.2; P = 0.03). Of note, in these areas, en face AO IR images revealed cone photoreceptors as hyperreflective dots over the background reflectivity (mean cone density 3,271 ± 1,109 cones per square millimeter). Microperimetry demonstrated residual function in areas of foveal sparing detected by confocal scanning laser ophthalmoscope near-IR autofluorescence. CONCLUSION: Adaptive optics allows the appreciation of differences in reflectivity between regions of GA and foveal sparing. Preservation of functional cone photoreceptors was demonstrated on en face AO IR images in areas of foveal sparing detected by confocal scanning laser ophthalmoscope near-IR autofluorescence.

TYPE 2 NEOVASCULARIZATION SECONDARY TO AGE-RELATED MACULAR DEGENERATION IMAGED BY OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: Optical coherence tomography angiography is a novel and noninvasive technique for imaging retinal microvasculature by detecting changes in reflectivity that is related to blood flow. The purpose of this study was to describe Type 2 neovascularization characteristics in age-related macular degeneration using optical coherence tomography angiography. METHODS: Fourteen eyes of 14 consecutive patients with Type 2 neovascularization were prospectively included. All patients underwent a complete ophthalmological examination, including color and infrared fundus photography, fluorescein and indocyanine green angiography, spectral domain optical coherence tomography angiography, and optical coherence tomography angiography. RESULTS: In all cases, Type 2 lesions could be detected by optical coherence tomography angiography, presenting as a hyperflow lesion in the outer retina, with a glomerulus (4/14) or medusa shape (10/14), surrounded by a dark halo. The superficial layer and the deep retina showed no abnormal flow. Surprisingly, the Type 2 lesions could also be observed in the presumed choriocapillaris layer. These glomerulus- or medusa-shaped lesions were connected, in 10/14 eyes, to a thicker main branch, which seemed to continue deep into the choroidal layers. CONCLUSION: Optical coherence tomography angiography may be a new imaging method for the diagnosis of Type 2 neovascularization in clinical routine. However, the specificity of the features needs to be investigated in further studies.

En face enhanced depth imaging optical coherence tomography features in adult onset foveomacular vitelliform dystrophy.

BACKGROUND: Our purpose was to describe the different morphological features in adult onset foveomacular vitelliform dystrophy (AOFVD), using en face enhanced depth imaging (EDI) spectral-domain optical coherence tomography (SD-OCT). METHODS: Thirty eyes of 22 consecutive patients presenting with diagnosis of AOFVD were enrolled. Diagnosis of AOFVD was concluded based on fundus examination, autofluorescence imaging, fluorescein angiography and SD-OCT. En face OCT imaging was obtained with the Spectralis EDI SD-OCT; 97 inverted sections (nine averaged B-scans per image) were acquired. RESULTS: On en face OCT, vitelliform lesions appeared as regular concentric rings of different reflectivity. From the periphery to center of the ring, we observed: (1) the hypereflective ring representing the inner segment/ outer segment (IS/OS) junction, which was continuous in 23 out of 30 eyes, and (2) a well-detectable hyporeflective ring between the IS/OS junction and vitelliform material in 20 out of 30 eyes; the innermost composant of the lesion was hypereflective, and it corresponded to vitelliform material. In eight out of 30 eyes, a hyporeflective "croissant"-shaped lesion with inferior concavity in the upper part of the hyperreflective material was present. Hypereflective retinal pigment epithelium (RPE) elevations or bumps were detected in 25 out of 30 eyes. These areas of focal RPE thickening or bumps appeared to be intensely hypereflective on infrared reflectance imaging. CONCLUSION: En face imaging of the retina helps visualizing the distribution of vitelliform material in AOFVD. The sedimentation of vitelliform lesions is characterized by a upper "croissant"-shaped hypoflectivity. The bumps/thickening of RPE appeared as hypereflective lesions on IR imaging.

Genetic and environmental factors associated with reticular pseudodrusen in age-related macular degeneration.

PURPOSE: To analyze the genetic and environmental factors associated with reticular pseudodrusen (RPD) in age-related macular degeneration (AMD). METHODS: In a large population, AMD patients (n = 519) with and without RPD were assessed with a standardized examination including infrared images and spectral domain optical coherence tomography scans. Three groups were defined: Group 1: AMD patients with RPD (n = 105); Group 2: AMD patients without RPD (n = 414); and Group 3: controls with no AMD and no RPD (n = 430). Four genes associated with AMD (CFH, ARMS2/HTRA1, C3, apolipoprotein E) and environmental factors were assessed between the 3 groups. RESULTS: None of the environmental factors studied were more significantly associated to either Group 1 or Group 2. The odds ratios and 95% confidence intervals for individuals homozygous for the CFH risk allele were 4.0 (2.1-7.7) ([95% confidence interval: 2.1-7.7]; P < 0.0004) in Group 1 and 4.3 ([2.6-7.1]; P < 0.0004) in Group 2, compared with Group 3. The odds ratios for individuals homozygous for the ARMS2 risk allele for Groups 1 and 2 compared with Group 3 were 16.3 ([7.6-35.4]; P < 0.0004) and 11.9 ([6.3-22.3]; P < 0.0004), respectively. None of the genotypes studied were more significantly associated to Group 1 than Group 2. CONCLUSION: Genotypes known to be associated with AMD were similarly observed in patients with and without RPD.

Foveal Hypoplasia in a Patient With High Myopia: Clinical and Imaging Diagnosis.

The authors present an unusual case of a 6-year-old boy with myopia and foveal hypoplasia who was diagnosed by optical coherence tomography angiography. This case report presents the importance of using optical coherence tomography angiography in the diagnosis of a different etiology. [J Pediatr Ophthalmol Strabismus. 2022;59(2):e23-e24.].

Long-term follow-up of retinal sensitivity assessed by microperimetry in patients with internal limiting membrane peeling.

PURPOSE: To evaluate anatomical and functional changes in patients with vitreomacular interface disease after internal limiting membrane (ILM) peeling, using microperimetry along with usual clinical and multimodal retinal imaging. METHODS: Patients with vitreomacular interface disease requiring vitrectomy underwent multimodal retinal evaluation, including visual acuity assessment, fundus color photograph, Spectral-Domain Optical Coherence Tomography, Optical Coherence Tomography-Angiography, and microperimetry. They were examined at baseline (M0), 6 months (M6) and 18 months (M18) after surgery. Retinal sensitivity was subdivided into three concentric polygons: Large, Medium, Small. RESULTS: Eleven eyes of 11 patients were analyzed, including 10 epiretinal membranes (ERMs). Best-corrected visual acuity (BCVA) improved in all patients from 0.51 logarithm of the minimal angle of resolution (logMAR) to 0.067 (p = 0.0074). Retinal sensitivity improved between M0 and M6 in all polygons and continued to improve between M6 and M18 for polygons Medium (M) and Small (S) with no statistical significance. At M18, BCVA and retinal sensitivity were similar in the operated eye compared with the fellow eye for all patients. Dissociated optic nerve fiber layer appearance was observed in 8 patients at M18. It was not correlated with either retinal sensitivity or BCVA or microscotomas. No recurrence of ERM or macular hole occurred during follow-up. CONCLUSION: After surgery, the retinal sensitivity assessed by microperimetry gradually improved until the 18th month and was not different from the values of the fellow eye. These results seemed to confirm that ILM peeling can be an effective and safe technique to treat patients with vitreomacular interface disease.