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PURPOSE To describe four eyes of three patients with presumed acute fovealitis to expand the clinical variants of this recently described disorder. METHOD The patients underwent a comprehensive ophthalmic examination, including multimodal imaging and electrophysiological tests. RESULTS Three female patients aged from 18 to 24 years presented sudden central visual disturbances in one or both eyes. The visual acuity ranged from 20/25 to 20/70 in the affected eyes. All of them showed a subtle yellowish lesion in the foveola. Fundus autofluorescence and fluorescein angiography were unremarkable. Optical coherence tomography disclosed focal disarrangement of the outer retinal layers restricted to the fovea and hyperrefective lesions above the external limiting membrane. Multifocal electroretinography responses were attenuated. The electrooculogram response was normal. All patients recovered normal visual acuity and the outer retinal layers. CONCLUSION Attenuated multifocal electroretinography foveal response and normal electrooculogram are newly described clinical findings in patients with acute fovealitis.

Purpose To compare the outcomes of using an internal limiting membrane (ILM) flap and the conventional ILM peel technique for small- or medium-sized full-thickness macular hole (FTMH) repair. Design Retrospective, interventional case series. Methods Eyes with an FTMH ≤ 400 µm that underwent vitrectomy with either a single-layer inverted ILM flap (flap group, 55 eyes) or an ILM peel (peel group, 62 eyes) were enrolled. Best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) measurements were obtained preoperatively and at 1, 3, 6, and 12 months postoperatively. Results Primary hole closure was achieved in 54 (98%) and 60 (97%) eyes in the flap and peel groups, respectively. The preoperative and postoperative 12-month BCVA were comparable between the groups but were significantly better in the flap than in the peel groups at 1 month (logMAR, mean ± SD, 0.83 ± 0.43 vs. 1.14 ± 0.50, P = 0.001), 3 months (0.58 ± 0.33 vs. 0.82 ± 0.43; P = 0.002), and 6 months (0.56 ± 0.32 vs. 0.72 ± 0.48; P = 0.028). In the flap group, foveal gliosis was less common than the peel group at 1 month (P = 0.030) and restored external limiting membrane and interdigitation zone was more common at 3 months (P = 0.046 and Conclusions Both the single-layer ILM flap and conventional ILM peel techniques closed FTMHs and improved vision. ILM flaps were associated with better visual outcomes up to 6 months postoperatively and should be considered in FTMHs ≤ 400 µm.

To assess factors associated with external limiting membrane (ELM)/ellipsoid zone (EZ) damage after pars plana vitrectomy (PPV) for epiretinal membrane and evaluate ELM/EZ damage impact on functional and anatomical outcomes.Patients who underwent PPV with epiretinal membrane ± inner limiting membrane peeling were retrospectively analyzed. Best-corrected visual acuity and central macular thickness were longitudinally collected based on the available follow-up. Demographic data, clinical data, and surgical details were included in logistic regression models having ELM/EZ damage as a binary outcome.Overall, 179 eyes (171 patients) were included; 93 had a 12-month follow-up. Thirty-four eyes (19%) had ELM/EZ damage after surgery; in nine eyes (5%), ELM/EZ damage persisted at 12 months. Phacoemulsification during PPV (odds ratio = 6.97; P = 0.007) and ELM/EZ damage before PPV (odds ratio = 6.91; P = 0.007) were risk factors for postoperative ELM/EZ disruption. Thicker outer nuclear layer (P = 0.002), thicker ectopic inner foveal layer (P0.001), and higher endoillumination power (P = 0.03) were associated with slower visual recovery. Inner limiting membrane peeling (P = 0.04) was associated with slower anatomical recovery.Cataract extraction and outer retinal damage before PPV are associated with higher risk of photoreceptor damage postoperatively. The rate of visual improvement varies as a function of retinal layers' distortion before surgery; additional retinal manipulation slows restoration of the macular anatomy.

To identify the eyes with macular edema (ME) due to a branch retinal vein occlusion (BRVO) that have good visual acuity during the continuous anti-vascular endothelial growth factor (anti-VEGF) treatment based on the patients’ clinical information and optical coherence tomography (OCT) images by using machine learning. Sixty-six eyes of 66 patients received 1 anti-VEGF injection followed by repeated injections in the pro re nata (PRN) regimen for 12 months. The patients were divided into two groups: those with and those without good vision during the 1-year experimental period. Handcraft features were defined from the OCT images at the time of the first resolution of the ME. Variables with a significant difference between the groups were used as explanatory variables. A classifier was created with handcrafted features based on a support vector machine (SVM) that adjusted parameters for increasing maximal precision. The age, best-corrected visual acuity (BCVA) at the baseline, BCVA at the first resolution of the ME, integrity and reflectivity of the external limiting membrane (ELM), the ellipsoid zone (EZ), and area of the outer segments of the photoreceptors were selected as explanatory variables. The classification performance was 0.806 for accuracy, 0.768 for precision, 0.772 for recall, and 0.752 for the F-measure. The use of the SVM of the patient’s clinical information and OCT images can be helpful for determining the prognosis of the BCVA during continued pro re nata anti-VEGF treatment in eyes with ME associated with BRVO.

Background/aimsTo determine whether a combination of baseline and change in spectral domain-optical coherence tomography (SD-OCT)-based biomarkers can predict visual outcomes in eyes with diabetic macular oedema (DMO) treated with antivascular endothelial growth factors (VEGF) injections.MethodsThis is a retrospective cohort study conducted in Hong Kong, China. 196 eyes with centre-involving DMO, who received anti-VEGF injections between 1 January 2011 and 30 June 2018 were recruited. Medical records of the participants were retrieved retrospectively, visual acuity (VA) at baseline, 6, 12 and 24 months and SD-OCT before initiation and after completion of anti-VEGF treatment were obtained. The SD-OCT images were evaluated for the morphology of DMO, vitreomacular status, presence of disorganisation of retinal inner layers (DRIL), sizes of intraretinal cysts, visibility of external limiting membrane (ELM), ellipsoid zone (EZ) and cone outer segment tip (COST) and the presence of hyper-reflective foci in retina or the choroid.ResultsThe presence of baseline DRIL, hyper-reflective foci in retina and disruption of ELM/EZ and COST were associated with worse baseline and subsequent VA up to 24 months after treatment. Improvement in DRIL (p=0.048), ELM/EZ (p=0.001) and COST (p=0.002) disruption after treatment was associated with greater improvement in VA at 12 months. Eyes with cystoid macular oedema (p=0.003, OR=8.18) and serous retinal detachment (p=0.011, OR=4.84) morphology were more likely to achieve at least 20% reduction in central subfield thickness.Conclusion and relevanceBaseline SD-OCT biomarkers and their subsequent change predict VA and improvement in vision in eyes with DMO treated with anti-VEGF injections. We proposed an SD-OCT-based system that can be readily used in real-life eye clinics to improve decision making in the management of DMO.

Purpose: to establish the tomographic parameters to predict the recurrent of macular edema due to retinal vein occlusion.Patients and methods. This is a retrospective study of 54 patients (54 eyes) with macular edema, no more than 3 months old, who had recurrent of macular edema after 3 intravitreal injections of aflibercept. Standard ophthalmological examination, spectral optical coherence tomography, intravitreal injections of aflibercept according to instruction, and statistical analysis of the data were conducted.Results. Recurrence of macular edema developed on average 6.3 ± 1.2 weeks after three injections of aflibercept. We identified of the most significant prognostic tomographic parameters affecting the recurrent of macular edema during intravitreal injections of aflibercept — central foveal thickness > 500 μm (OR 2.1, p = 0.01), the presence of serous retinal detachment (OR 5.1, p = 0.001), the presence of hyperreflective foci (OR 3.7, p = 0.03), alteration of external limiting membrane (OR 4.7, p = 0.01), disruption of the photoreceptor innersegment/outer segment junction (OR 3.4, p = 0.01), disruption of retinal pigment epithelium (OR 2.1, p = 0.02).Conclusion: the recurrent of macular edema with retinal vein occlusion during antiangiogenic therapy depends on baseline tomographic parameters. Our results can be important in predicting the duration and effectiveness of antiangiogenic therapy in a particular patient at the beginning of the disease, which makes the approach to management more personalized, promising in economic, social and psychological aspects.

International audience; Purpose: To investigate cone density in the asymptomatic fellow eye of patients with unilateral central serous chorioretinopathy (CSCR). Methods: Seventeen asymptomatic fellow eyes of patients with unilateral CSCR and 17 eyes of aged-matched and gender-matched healthy controls underwent adaptive optics ophthalmoscopy. Cone density and spacing were assessed at the fovea. Clinical and multimodal imaging findings were also recorded. Results: In the CSCR group, the patient mean age was 48.9 ± 9.8 years. The mean (±SD) subfoveal choroidal thickness was 417.8 ± 125.2 mm. The foveal external limiting membrane and ellipsoid zone were intact in all patients. Adaptive optics fundus imaging showed a significant decrease in cone density at 2°of eccentricity nasal and temporal to the fovea in asymptomatic fellow eyes of patients with unilateral CSCR compared with controls (P = 0.001 and P = 0.027, respectively). No statistically significant difference in cone density was found at 4°of eccentricity nasal and temporal to the fovea between both groups. Conclusion: Asymptomatic fellow eyes of patients with unilateral CSCR showed a reduced density of foveal cones in the absence of a decreased visual acuity and photoreceptor line disruption on optical coherence tomography. These results suggest that the photoreceptors could be damaged independently of the occurrence of a serous retinal detachment.

Purpose To study the natural history of optical coherence tomography (OCT) imaging-based findings seen in non-exudative age-related macular degeneration (neAMD) and model their relative likelihood in predicting development of incomplete retinal pigment epithelium and outer retinal atrophy (iRORA), complete retinal pigment epithelium and outer retinal atrophy (cRORA), and neovascular AMD (nAMD). Methods Retrospective chart review was performed at two academic practices. Patients diagnosed with neAMD for whom yearly OCT scans were obtained for at least 4 consecutive years were included. Baseline demographic, visual acuity, AREDS staging, and OCT data were collected. OCTs were assessed for the presence or absence of eleven features previously individually associated with progression of neAMD, both at baseline, and on all subsequent follow-up scans. Likewise, charts were reviewed to assess visual acuity and staging of NEAMD at all follow-up visits. A multivariate regression analysis was constructed to determine predictors of iRORA, cRORA, and nAMD. Results A total of 107 eyes of 88 patients were evaluated. Follow-up included yearly OCTs obtained over at least 4 consecutive years follow-up (range: 50-94 months). During the follow-up period, 17 eyes progressed to iRORA while 25 progressed to cRORA and 16 underwent conversion to nAMD. Predictors of conversion to iRORA and cRORA included integrity of the external limiting membrane (p = 0.02), the ellipsoid zone (p = 0.01), and the cone outer segment line (p = 0.003) and the presence of intraretinal hyporeflective spaces (p = 0.009), drusen ooze (p = 0.05), and drusen collapse (p = 0.001). OCT features predictive of conversion to nAMD included outer nuclear layer (ONL) loss (p = 0.01), presence of intraretinal (p = 0.001) and subretinal (p = 0.005) hyporeflective spaces, and drusen collapse (p = 0.003). Conclusion Of these multiple factors predictive of progression of neAMD, the OCT feature most strongly correlated to progression to iRORA/cRORA was drusen collapse, and the feature most predictive of conversion to nAMD was the presence of intraretinal hyporeflective spaces.

Purpose To describe the clinical and multimodal imaging (MMI) features of bacillary layer detachment (BD), and its response to intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy, in eyes with macular neovascularization (MNV). Design Retrospective, observational case series. Methods Fourteen eyes (14 patients, 7 male) were imaged with spectral-domain optical coherence tomography (OCT), and either fluorescein angiography or OCT angiography. Therapeutic response was monitored with serial imaging and best-corrected visual acuity (BCVA) assessments. Results Mean age was 75±13 (range: 45-96) years, with mean follow-up duration of 27±21 (range: 1-56) months. Neovascular age-related macular degeneration (nAMD) was found in 71% (10/14) eyes. Type 2 MNV lesions were associated with BD in all 14 eyes. Subretinal hemorrhage was noted in 79% (11/14) eyes. BD promptly resolved following intravitreal anti-VEGF therapy in all eyes. Baseline BCVA improved from LogMar 0.84±0.32 (Snellen equivalent 20/138) to LogMar 0.48±0.31 (Snellen equivalent 20/60) at last follow-up, with treatment of the MNV. Conclusions Type 2 MNV and subretinal hemorrhage are associated with BDs, which may be due to a rapid influx of exudative fluid into the potential space between the external limiting membrane and ellipsoid zone. Intravitreal anti-VEGF therapy results in rapid resolution of BDs and visual improvement in most eyes.

International audience; Purpose: To describe the value of integrating phenotype/genotype data, disease staging, and evaluation of functional vision in patient-centered management of retinal dystrophies.Methods: (1) Cross-sectional structure-function and retrospective longitudinal studies to assess the correlations between standard fundus autofluorescence (FAF), optical coherence tomography, visual acuity (VA), and perimetry (visual field [VF]) examinations to evaluate photoreceptor functional loss in a cohort of patients with rod-cone dystrophy (RCD); (2) flood-illumination adaptive optics (FIAO) imaging focusing on photoreceptor misalignment and orientation of outer segments; and (3) evaluation of the impact of visual impairment in daily life activities, based on functional (visual and mobility) vision assessment in a naturalistic environment in visually impaired subjects with RCD and subjects treated with LuxturnaⓇ for RPE65-related Leber congenital amaurosis before and after therapy.Results: The results of the cross-sectional transversal study showed that (1) VA and macular sensitivity were weakly correlated with the structural variables; and (2) functional impairment (VF) was correlated with reduction of anatomical markers of photoreceptor structure and increased width of autofluorescent ring. The dimensions of the ring of increased FAF evolved faster. Other criteria that differed among groups were the lengths of the ellipsoid zone, the external limiting membrane, and the foveal thickness. FIAO revealed a variety of phenotypes: paradoxical visibility of foveal cones; heterogeneous brightness of cones; dim, inner segment-like, and RPE-like mosaic. Directional illumination by varying orientation of incident light (Stiles-Crawford effect) and the amount of side illumination (gaze-dependent imaging) affected photoreceptor visibility. Mobility assessment under different lighting conditions showed correlation with VF, VA, contrast sensitivity (CS), and dark adaptation, with different predictive values depending on mobility study paradigms and illumination level. At high illumination level (235 lux), VF was a predictor for all mobility performance models. Under low illumination (1 and 2 lux), VF was the most significant predictor of mobility performance variables, while CS best explained the number of collisions and segments. In subjects treated with LuxturnaⓇ, a very favorable impact on travel speed and reduction in the number of collisions, especially at low luminance, was observable 6 months following injection, in both children and adults.Conclusions: Our results suggest the benefit of development and implementation of quantitative and reproducible tools to evaluate the status of photoreceptors and the impact of both visual impairment and novel therapies in real-life conditions. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

PURPOSE To assess the effect of an internal limiting membrane flap (IF) in macular hole surgery on the best-corrected visual acuity (BCVA) and integrity of the ellipsoid zone (EZ) and external limiting membrane. METHODS Patients were included who had successful surgery for macular hole

Background To analyze the long-term effects of persistent subretinal fluid (SRF) on visual/anatomic outcomes according to the type of macular neovascularization (MNV) during relaxed treat-and-extend regimen with anti-vascular endothelial growth factor (anti-VEGF) agents in age-related macular degeneration (AMD) patients. Methods Patients with fovea-involving type 1 or type 2 MNV, treated with a relaxed treat-and-extend regimen for 2 years were retrospectively reviewed. Eyes with SRF observed more than three times per year were defined as the ‘persistent SRF (+) group’. To exclude the effects of IRF as much as possible, the eyes with persistent IRF were excluded. The effects of persistent SRF on the best-corrected visual acuity (BCVA), central subfield retinal thickness (CST), and changes in the photoreceptor layer (PRL) thickness and outer retinal bands (external limiting membrane, ellipsoid zone, and cone outer segment tip line) after anti-VEGF injection were analyzed for each MNV type. Results Seventy-seven eyes with type 1 MNV (44 eyes with persistent SRF) and 53 eyes with type 2 MNV (18 eyes with persistent SRF) were enrolled. Following a relaxed treat-and-extend regimen with anti-VEGF agents, BCVA and CST improved for each MNV type. In comparison between persistent SRF (+) and persistent SRF (−) group, there were no differences in the amount of change in BCVA and CST between the two groups for each MNV type during 2-year follow-up periods. In addition, there were no differences in the amount of reduction in PRL thickness and state of the outer retinal bands between the two groups for each MNV type. Conclusions Using a relaxed treat-and-extend regimen with anti-VEGF agents, persistent SRF did not have additional effects on visual and anatomic outcomes by 2 years, regardless of the MNV type.

To quantify aniseikonia following intravitreal ranibizumab (IVR) in patients with branch retinal vein occlusion (BRVO) and assess the relationship between aniseikonia and retinal microstructure. Prospective observational study. This study included 50 patients undergoing IVR treatment for unilateral BRVO. The degree of aniseikonia and best-corrected visual acuity (BCVA) was examined, and retinal microstructure was assessed with optical coherence tomography (OCT) before and 1, 2, 3, 4, 5, and 6 months after treatment. Based on OCT images, we assessed central retinal thickness (CRT), presence of the epiretinal membrane, and serous retinal detachment (SRD), as well as status of the external limiting membrane and ellipsoid zone. At baseline, mean aniseikonia was − 1.0 ± 2.5%, ranging from − 11.0 to + 6.0%. Nine out of 50 patients had micropsia (18%), one had macropsia (2%), and 40 had no aniseikonia (80%). After 6 months of treatment, mean aniseikonia was − 0.7 ± 1.5%, ranging from − 4.5 to + 3.5%. BCVA significantly improved after treatment (P

Purpose: To report novel retinal findings in two male patients with mucopolysaccharidosis type II (Hunter syndrome) receiving long-term human recombinant idursulfase enzyme replacement therapy.Method: Two males aged 19 and 26 years who had received enzyme replacement therapy for 12 and 13 years, respectively, with good compliance and no infusion-related reactions, were examined clinically and underwent optical coherence tomographic scanning of the retina and electroretinography testing.Results: Case 1 had visual acuity 20/32 in each eye and case 2 had visual acuity 20/25 in each eye. Both patients had clinically unremarkable anterior segment and fundus examinations. Ocular coherence tomography imaging in both patients showed thickening of the external limiting membrane with hyperreflective material in at least one eye each. One patient had bilateral foveoschisis and the other had mild foveal hypoplasia. Electroretinography showed a negative response in the patient with foveoschisis and reduced amplitudes in the patient with foveal hypoplasia.Conclusions: These two patients with Hunter syndrome receiving idursulfase treatment both have subfoveal deposition of hyperreflective material in the external limiting membrane despite good compliance and tolerance of the standard dose of enzyme therapy for this disorder. One patient has developed foveoschisis and negative electroretinogram suggesting abnormality of inner retinal function. Further studies are needed to determine the nature of the hyperreflective material, as well as the effect of systemic treatment on retinal findings in patients with mucopolysaccharidosis type II.

Purpose To assess the in vivo physiology of retinal reattachment in humans using swept-source optical coherence tomography (SS-OCT) in real time. Design Prospective case series. Methods Fifteen consecutive patients with fovea-involving rhegmatogenous retinal detachment were undergoing pneumatic retinopexy. SS-OCT was performed at presentation and frequent intervals immediately after pneumatic retinopexy. The primary outcome was longitudinal assessment of early postoperative SS-OCT to establish stages of reattachment. Results Most patients (93.3%, 14/15) achieved successful reattachment at the median follow-up duration of 13 weeks (interquartile range 7.5-18.0). Reattachment occurred in 5 specific stages: 1) redistribution of fluid and approach of the neurosensory retina toward the retinal pigment epithelium occurred in 100% (15/15); 2) reduction in cystoid macular edema and improvement of outer retinal corrugations was achieved in 100% (15/15); 3) initial contact of the neurosensory retina to the retinal pigment epithelium occurred completely in 66.7% (10/15); 4) deturgescence of the inner and outer segments of the photoreceptors occurred in 66.7% (10/15); and 5) recovery of photoreceptor integrity occurred in 3 specific substages: 5A) external limiting membrane recovery (10/15, 66.6%); 5B) ellipsoid zone recovery (9/15, 60%); and 5C) interdigitation zone/foveal bulge recovery (3/15, 20%). Twenty percent (3/15) had delayed progression through stage 2, characterized by formation of outer retinal folds. Similarly, 33.3% (5/15) developed residual subfoveal fluid blebs (delayed progression to stage 3). Conclusions This study characterizes the in vivo physiology of retinal reattachment in humans using high-resolution SS-OCT that occurs in 5 specific stages. Delayed progression through certain stages was characterized by postoperative anatomic abnormalities. Am J Ophthalmol 2021;221:•••–•••. © 2021 Elsevier Inc. All rights reserved.

PURPOSE To report spectral domain optical coherence tomography (OCT) findings of a patient who experienced bilateral visual loss after a motorcycle accident. METHODS A 51-year-old man presented to the emergency department complaining of bilateral visual loss after a motorcycle falling down. A complete ophthalmologic examination and OCT testing were made on the same day of the accident. Follow-up was made at 2 days, 2 weeks, 5 months, and 12 months adding central visual field assessment using Humphrey automated perimetry. RESULTS At presentation, best-corrected visual acuity was 20/200 in both eyes, anterior segment was normal, and fundus examination showed a bilateral macular edema confirmed by OCT. After 2 days, visual acuity recovered to 20/25. Optical coherence tomography findings showed foveal detachment, hyperreflective clump below external limiting membrane, and hyperreflectivity of Henle layer nasally to the fovea. After 15 days, visual acuity was 20/20, but vision was altered by a paracentral scotoma and some irregularities of OCT findings persisted. At 1 year of follow-up, best-corrected visual acuity was 20/20, and paracentral scotoma was very tiny in the right eye, whereas larger and deeper in the left eye. Optical coherence tomography was normal in the right eye, whereas some fragmentations of interdigitation zone were still evident in the left eye. CONCLUSION We report a case of bilateral whiplash maculopathy from vitreoretinal traction subsequent to road traffic accident. After 1 year of follow-up, visual acuity was restored but paracentral scotoma persisted. Optical coherence tomography appearance of the left eye was still abnormal.

Purpose To report a case of photoreceptor restitution and vision improvement with pneumatic compaction treatment of acute subfoveal hemorrhage in a patient with angioid streaks associated with pseudoxanthoma elasticum, observed by sequential fundus photography, spectral domain optical coherence tomography, and fundus autofluorescence. Methods Findings on initial and sequential clinical examinations, fundus autofluorescence, and spectral domain optical coherence tomography are presented, before and after pneumatic compaction, demonstrating the course of compaction and resolution of subfoveal hemorrhage and status of the foveal ellipsoid zone and external limiting membrane. Sequential improvements in oxygen and nutrient diffusion are calculated using Fick's law of diffusion. Findings are compared with previous reports regarding the natural history of similar patients. Results Rapid compaction of subfoveal hemorrhage occurred, resulting in an 89% improvement in oxygen diffusion in 15 days. No centrifugal movement of subfoveal hemorrhage occurred, potentially minimizing photoreceptor-shearing injury. Ultimately, resorption of all hemorrhage occurred with reestablishment of the foveal ellipsoid zone and external limiting membrane and minimal juxtafoveal subretinal fibrosis; best-corrected visual acuity improved to 20/40: an advantage over natural history based on published reports. Conclusion Pneumatic compaction in patients with acute subfoveal hemorrhage secondary to angioid streaks associated with pseudoxanthoma elasticum compacts subfoveal hemorrhage, therefore improving oxygen and nutrient diffusion. This potentially spares foveal photoreceptors of ischemic and shearing injury, theoretically reducing subfoveal fibrosis and improving vision prognosis in these patients.

PURPOSE To present a case of macular hole associated with macular telangiectasia Type 2 (Mac-Tel 2) which underwent spontaneous closure. METHODS A 58-year-old woman is admitted with complaints of blurred and distorted vision. Optical coherence tomography, fundus autofluorescence, and optical coherence tomography angiography were performed for diagnosis and follow-up. RESULTS Optical coherence tomography revealed hyporeflective cavitations in both eyes, and full-thickness macular hole covered with internal limiting membrane drape in the left eye. Fundus autofluorescence showed loss of hypoautofluorescence in temporal parafoveal area in the right eye, and centrally in the left one. Vascular irregularities were detected in optical coherence tomography angiography images. The patient was diagnosed as Mac-Tel 2. During the follow-up, the macular hole underwent a process of spontaneous closure, starting as bridging at the level of external limiting membrane and outer nuclear layer followed by further repairment and organization of the outer plexiform layer, accompanied with visual gain. CONCLUSION Spontaneous closure of macular hole in patients with Mac-Tel 2 is a rare entity. We hypothesize that extension or proliferation of Muller cells, which leads to reconstruction of normal foveal structure, is the main mechanism for this phenomenon.

Purpose The purpose of this study is to investigate anatomic and morphologic features of inner and outer retinal layers in patients recovered from COVID-19 with Spectral Domain Optical Coherence Tomography (SD-OCT), whether correlate with any symptoms during disease process. Methods 32 patients recovered from COVID-19 and age- and gender-matched 36 healthy controls were included in this cross-sectional study. Ganglion cell-inner plexiform layer, macular and peripapiller retinal nerve fiber layer (RNFL), inner nuclear layer (INL), outer nuclear layer (ONL), outer plexiform layer (OPL) and the outer retinal hyperreflective bands including external limiting membrane (ELM), ellipsoid zone (EZ) and interdigitation zone (IZ) were examined with SD-OCT. The differences of each retinal layers thickness among subgroup analysis of ocular pain and headache were also compared. Results Macular RNFL of inner and outer nasal and outer inferior quadrants were thinner in COVID-19 patients compared to healthy control group (p = 0.046, p = 0.014 and p = 0.016, respectively). Thinning in outer superior quadrant of GCIPL and INL quadrants were detected in patients with headache (p = 0.026 and p = 0.01). Superonasal and inferotemporal sectors of pRNFL were thinner in patients with ocular pain compared to patients without ocular pain (p = 0.024 and p = 0.015). Integrity of EZ, ELM and IZ was evaluated as continuous line and protected on each OCT scans. Conclusion The study demonstrated convincing evidence that SARS-CoV-2 can affect the inner and outer retinal layers, with subclinical localized alterations, particularly in patients with headache and ocular pain symptoms during COVID-19 period. Supplementary Information The online version contains supplementary material available at 10.1007/s10792-021-01952-5.

We present a patient with idiopathic intracranial calcifications with simultaneous involvement of sclera, choroid, optic nerve, and trochlear apparatus. A 70-year-old woman with bilateral decreased vision was referred to our hospital. Ocular examinations revealed sclerochoroidal mass beneath superotemporal vascular arcade in macular area. Orbital CT scan shows bilateral calcification of dural optic nerve sheath and posterior wall of the globe as well as calcification in the trochlear apparatus and brain. Ultrasound showed highly reflective echogenic lesion with shadowing. OCT revealed rolling topography with thinning of the overlying choroid and outer nuclear layer as well as absence of the external limiting membrane and inner segment-outer segment junction. Slight irregular thickening of the retinal pigment epithelium is present. It is the first case of simultaneous bilateral dural optic nerve sheath and sclerochoroidal calcification.

PURPOSE To evaluate microstructural changes in cystoid macular edema in retinitis pigmentosa after intravitreal dexamethasone implant injection. METHODS In an extended cohort of a randomized trial of intravitreal dexamethasone implant for the management of retinitis pigmentosa-associated cystoid macular edema, microstructural changes during six months after the treatment were evaluated using spectral-domain optical coherence tomography. RESULTS Forty-two eyes were included, and all had cystoid space in the inner nuclear layer (INL) at baseline. No eyes showed subretinal fluid, and 28.6% showed hyperreflective foci. Among 38 eyes with cystoid space both in the INL and outer nuclear layer/Henle's layer, 13 (34.2%) showed complete resolution and 12 (31.6%) showed cystoid space only in the INL at 2 months after injection, whereas others showed persistent cystoid space in both layers. After complete resolution, cystoid space recurrence was earlier in the INL than in the outer nuclear layer/Henle's layer. Multivariable analysis showed that greater cystoid space area in the INL and outer nuclear layer/Henle's layer, presence of macular leakage, and longer intact external limiting membrane at baseline were associated with greater cystoid space area decrease after the treatment. CONCLUSION Resolution and recurrence pattern of retinitis pigmentosa-associated cystoid macular edema after dexamethasone treatment showed that the INL is the primary layer of cystic change, and this suggests its pathogenesis is most likely caused by Muller cell dysfunction.

Background: Diabetic retinopathy is a common deficiency of diabetes mellitus. Diabetic macular ischemia [DMI] is a permanent form of diabetic maculopathy, and its presence reduces the potential benefits of diabetic retinopathy management. Optical coherence tomography [OCT] is used to precisely and reliably measure the macular thickness and outline the retinal layers. Optical coherence tomography angiography [OCTA] can be utilized as a reliable tool to classify the superficial capillary plexus [SCP], the deep capillary plexus [DCP] and the capillary non-perfusion [NP]. Aim of the work: The current research aimed to investigate the correlation between macular non-perfusion that diagnosed by OCTA and patterns of macular layers that diagnosed by OCT scans through the same parts, in a trial to help in the evaluation of both structural and vascular integrity. Patients and Methods: The study included 250 eyes of 125 diabetic patients. All study participants were scanned by OCTA. OCT angiograms were re-sampled with OCT scans from the same region, permitting synchronous evaluation of structure and blood flow. Results: 250 of 125 diabetic patients were categorized into two groups according to capillary NP, ischemic [G1] and non-ischemic [G2]. In current study the incidence of DMI was 40%. The incidence of DCPNP was 100% in eyes with DMI while the incidence of SCPNP was 71%. The incidence of foveal avascular zone [FAZ] irregularity, disorganization of the retinal inner layers [DRIL], inner/outer segment IS/OS and external limiting membrane ELM disruptions were 100%, 83%, 95%, 71% respectively among eyes with DMI. DCPNP was more found in all eyes with FAZ irregularity, DRIL, IS/OS and ELM disruption than SCP NP which makes it as the central cause of structural changes in the retina during ischemia. There was a strong positive correlation between the appearance of FAZ irregularity, DRIL, IS/OS and ELM disruption with each of the duration and severity of DR. Conclusion: FAZ irregularity, DRIL, IS/OS and ELM disruption are considered reliable OCT/OCTA findings that reflect an underling DMI and their existence can influence the visual prognosis.

To investigate the influence of age on the function and morphology of patients with myopic choroidal neovascularization (mCNV) and to evaluate the effect and prognostic factors of recurrence of Conbercept treatment on mCNV patients over 50 years. A total of 64 patients (64 eyes) with mCNV were enrolled in this retrospective study. The differences in baseline best-corrected visual acuity (BCVA) and morphological features on imaging between the younger group (˂ 50 years) and the older group (≥ 50 years) were analyzed. Of all, 21 eyes of 21 mCNV patients aged over 50 years who received Conbercept injection were further analyzed. Between the younger and the older group, significant differences were shown in mean BCVA (0.58 ± 0.28 vs 0.77 ± 0.31), subfoveal choroidal thickness (SFCT) (108.17 ± 78.32 μm vs 54.68 ± 39.03 μm) and frequency of vitreoretinal interface abnormalities (VIA) (2 vs 13), respectively (P

Sufian Elfandi,1 Sotaro Ooto,1 Manabu Miyata,1 Naoko Ueda-Arakawa,1 Yousif Subhi,1,2 Kenji Yamashiro,1 Hiroshi Tamura,1 Akio Oishi,1 Masayuki Hata,1 Nagahisa Yoshimura,1 Akitaka Tsujikawa1 1Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan; 2Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkCorrespondence: Sotaro OotoDepartment of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine Email ohoto@kuhp.kyoto-u.ac.jpPurpose: To compare the 12-month efficacy of intravitreous aflibercept (IVA) injection between eyes with pachychoroid neovasculopathy and neovascular age-related macular degeneration (AMD).Methods: Retrospective, comparative case series analysis. Twenty-seven eyes with pachychoroid neovasculopathy and sixty-three eyes with neovascular AMD. All patients received three initial monthly, followed by bimonthly, IVA injections.Results: Twelve months after initial treatment, the mean best-corrected visual acuity (BCVA) had improved both in pachychoroid neovasculopathy (from 0.28 to 0.14 logMAR; P = 0.001) and neovascular AMD (from 0.40 to 0.29 logMAR; P < 0.001). Twelve months after initial treatment, eyes with pachychoroid neovasculopathy exhibited decreased mean central retinal thickness (CRT) and subfoveal choroidal thickness (both, P < 0.001) and presence of polyps (P = 0.039) and improved integrity of external limiting membrane (ELM) (P = 0.008) and ellipsoid zone band (P = 0.001). At the 12-month follow-up, 77% and 68% of eyes with pachychoroid neovasculopathy and neovascular AMD, respectively, exhibited dry macula (P = 0.30). Baseline CRT was correlated with 12-month BCVA in eyes with pachychoroid neovasculopathy (P = 0.02). In eyes with neovascular AMD, CRT (P = 0.005) and presence of intact ELM (P = 0.007) were significant predictors of 12-month BCVA.Conclusion: Periodic IVA injection leads to anatomical and functional improvement in eyes with pachychoroid neovasculopathy and in eyes with neovascular AMD.Keywords: age-related macular degeneration, aflibercept, pachychoroid neovasculopathy, choroidal thickness

Diabetic macular edema (DME) is the most common cause of vision loss in diabetic retinopathy, affecting 1 in 15 patients with diabetes mellitus (DM). The disruption of the inner blood-retina barrier (BRB) has been largely investigated and attributed the primary role in the pathogenesis and progression in DME, but there is increasing evidence regarding the role of outer BRB, separating the RPE from the underlying choriocapillaris, in the occurrence and evolution of DME. The development of novel imaging technologies has led to major improvement in the field of in vivo structural analysis of the macula allowing us to delve deeper into the pathogenesis of DME and expanding our vision regarding this condition. In this review we gathered the results of studies that investigated specific outer BRB optical coherence tomography parameters in patients with DM with the aim to outline the current status of its role in the pathogenesis and progression of DME and identify new research pathways contributing to the advancement of knowledge in the understanding of this condition.

PURPOSE: To establish the morphological and functional parameters to predict the effectiveness of intravitreal injections (IVI) of ranibizumab in macular edema due to retinal vein occlusion and to develop a mathematical model for personalized treatment algorithms. MATERIAL AND METHODS: This is a retrospective study of 98 patients (98 eyes) with macular edema, who received IVI of ranibizumab and were followed up for 12 months. Spectral optical coherence tomography scans and best corrected visual acuity (BCVA) assessments were conducted every 3 months. Treatment outcome predictors were calculated based on logistic regression analysis. RESULTS: The most significant prognostic factors for the long-term BCVA were baseline BCVA (OR 11.1, p = 0.001), foveal volume (OR 10.8, p = 0.001), destruction of external limiting membrane (OR 15.8, p = 0.001), photoreceptor inner/outer segments (OR 11.1, p = 0.001) and retinal pigment epithelium (OR 9.1, p = 0.001). It has also been discovered that post-treatment BCVA correlated with the height of serous retinal detachment (SRD) (r = −0.4, p = 0.001), ganglion cell complex thickness (r = + 0.3, p = 0.01) and focal loss of ganglion cells (r =−0.3, p = 0.005). Patients without SRD required fewer ranibizumab injections (3.8 ± 1.1) for macular edema fluid resorption compared to those with SRD (5.7 ± 1.2, p = 0.03). A mathematical model for predicting and personalized approach therapy of ranibizumab has been obtained (accuracy of 89%). CONCLUSION: The effectiveness of IVI of ranibizumab depends on baseline morphological and functional changes. The obtained mathematical model allows for predicting the outcomes of therapy, determining individualized algorithms to increase the treatment effectiveness and to prevent low vision that corresponds to the principles of predictive, preventive, and personalized medicine.

Purpose: This study aimed to evaluate the optic coherence tomography (OCT) findings in patients with toxoplasmic retinochoroiditis (TRC). Methods: A total of 12 eyes of 12 patients with active TRC were included in the study. At baseline, at the first-month follow-up, at the sixth-month follow-up and at the 1-year follow-up, the TRC lesion OCT and macula OCT were evaluated. Results: Hyperreflectivity of the inner retinal layers and an increase in retinal thickness were observed on the OCT examinations of all the patients with an active TRC lesion. The retinal thickness decreased and the reflectivity of retinal layers was disorganized in the OCT images obtained in the follow-up period. Partial posterior hyaloid detachment (PHD) and no PHD were detected in 11 cases and 1 case, respectively. Epiretinal membrane (ERM) had developed in the adjacent region of the scar in 7 patients. With the regression of the lesion, the disruption of the ellipsoid zone (EZ), retinal pigment epithelium (RPE) and external limiting membrane (ELM) improved in the adjacent areas. In all the eyes, ERM and the PHD configuration did progress during the follow-up period. Vitreoschisis was found in 4 of the 11 patients with partial PHD. It was observed that ERM developed in all the patients with vitreoschisis. Conclusion: ERM and partial PHD were common in the TRC patients, and there was no progression during the follow-up period. Regeneration of the EZ, RPE and ELM was observed in the follow-up period.

Purpose To investigate morphological and functional outcomes of the inverted internal limiting membrane (I-ILM) flap technique in large (≥ 400 μm) idiopathic full-thickness macular holes (FTMH) over a follow-up period of 12 months. Methods In this retrospective study, 55 eyes of 54 consecutive patients were enrolled. Best-corrected visual acuity (BCVA) and spectral-domain optical coherence tomography (SD-OCT, Heidelberg, Spectralis) were performed preoperatively as well as 1, 3, 6, 9, and 12 months postoperatively. Special focus was put on the reintegration of outer retinal layers and the different ILM flap appearances. Results FTMH closure rate was 100% (55/55). BCVA significantly improved over the follow-up period of 12 months from 0.98 ± 0.38 LogMAR preoperatively to 0.42 ± 0.33 LogMAR at 12 months postoperatively (p Conclusion Our study highlights the favorable morphological and functional outcomes of the I-ILM flap technique in the short as well as in the long term. While complete ELM restoration revealed to be an important factor for improvement in BCVA, the different postoperative ILM flap appearances seem not to be related to BCVA.

The article analyzes the state of patients visual acuity after successful surgical treatment of retinal detachment. On the basis of gathered data, it was concluded that in case of detachment of the macula only in 50% of cases it is possible to increase visual acuity to 0.4 and higher. Restoration of visual functions continues for at least 6 months after the operation and is determined by the restoration of the structure of the outer segments of the photoreceptor cells. During this time, it is advisable to conduct drug therapy aimed at normalizing blood flow and functional activity of the retina. Visual functions recovery continues for at least 6 months after the operation and is connected with the restored structure of the outer segments of the photoreceptor cells. Important prognostic factors of central vision restoration in the postoperative period are visual acuity before surgery, duration of existence and height of macular detachment. Data on which of the methods of surgical treatment of retinal detachment allows to achieve higher visual acuity are contradictory. There is practically no data on the comparison of the effect on visual acuity of scleral buckling and vitrectomy in the long-term period, in patients with phakic eyes and with artiphakia. On visual acuity after fitting detachment of the macula may affect macular edema, epiretinal membrane formation and retinal folds, and edema of the peripapillary optic nerve head, progressive deterioration of blood flow in the basin of the central retinal artery, short posterior ciliary arteries and ophthalmic artery. It is believed that these factors are significantly more pronounced after scleral buckling than after vitrectomy. Some indicators of optical coherence tomography correlate with visual acuity after surgical treatment of retinal detachment: the state of the articulation line of the external and internal segments of the photoreceptors, as well as the state of the external limiting membrane.

Objective Diabetic retinopathy (DR), a microvascular complication of diabetes, is a leading cause of preventable blindness. Spectral domain optical coherence tomography (SD-OCT) provides cross-sectional and topographical imaging of the retina. SD-OCT resolves outer retinal layers into three hyperreflective bands—external limiting membrane (ELM), ellipsoid zone (EZ), and retinal pigment epithelium (RPE). In this article, we have studied the role of these outer retinal layers in structural and molecular changes taking place in DR. Materials and Methods Articles with clinical features, pathogenesis, diagnosis, and treatment of DR were thoroughly studied. Articles were searched on PubMed, MEDLINE, and Cochrane Library from 2000 to 2020. Studies focusing on the role of ELM, EZ, and RPE in pathogenesis of DR based on SD-OCT were included. Results The long-standing hyperglycemia leads to protein glycosylation resulting in formation of advanced glycation end products (AGEs). AGEs have an impact through their effect on retinal microvasculature, vascular endothelial growth factor (VEGF), intercellular adhesion molecule-1, nitrosative and oxidative stress, and vitamin D and calcium metabolism. All these factors have been linked with disruption of outer retinal layers. AGEs lead to vascular endothelial dysfunction and release of proangiogenic factors by increasing the expression of VEGF in retinal pericytes and RPE cells. This leads to leakage and fluid accumulation resulting in diabetic macular edema (DME). In DME, there is sequential disruption of ELM and EZ and decrease in visual acuity (VA). The RPE alterations have been reported to be associated with the severity of DR and decrease in VA. Anti-VEGF therapy, most common treatment of DME, leads to restoration of barrier effect of ELM, it was found to be restored first followed by EZ restoration. Newer anti-AGEs agents and their receptor blockers are being developed which have a positive effect on maintaining the health of RPE. Conclusion A complex molecular association exists between the structural changes in ELM, EZ, and RPE in DR. SD-OCT is an indispensable tool to study these changes as integrity of these outer layers of retina is essential for maintaining visual function of retina in DR.

We analysed the imaging findings of macular telangiectasia (MacTel) type 2 in Korea using spectral domain optical coherence tomography (SD-OCT) and investigated their relationship with visual acuity and clinical stages. A retrospective multicentre cross-sectional study was conducted in six tertiary hospitals in Korea and included 129 patients. We analysed all the SD-OCT images encompassing the macular area. Hyporeflective cavities (77.7%) were the most frequently detected abnormalities in SD-OCT. Disruption of the external limiting membrane, ellipsoid zone, and interdigitation zone were found in 67 (40.4%), 87 (52.4%), and 94 eyes (56.6%), respectively. Four eyes (2.4%) had lamellar macular hole, and five eyes (3.0%) full-thickness macular hole. Neovascularisation, either subretinal or intraretinal, was found in 14 eyes (8.4%). Eyes with outer retinal hyperreflective band disruption had lower visual acuity than those without them. The presented characteristic clinical features of OCT in MacTel type 2 can not only aid in differentiating this disease from others but are also helpful for better judgement of the disease stage in daily clinical practice. Inner retinal hyporeflective cavities without outer retinal abnormalities on SD-OCT, although classified as severity scale 3, could be considered a relatively early stage in the disease process in terms of vision.

PURPOSE To report the frequency, optical coherence tomography (OCT) findings, and visual and anatomic outcomes of patients with acute Vogt-Koyanagi-Harada disease presenting with the bacillary layer detachment (BLD) (intraretinal split at the photoreceptor inner segment myoid). METHODS This was a retrospective analysis of a consecutive series of patients with Vogt-Koyanagi-Harada disease having a minimum follow-up of 6 months. All patients had swept-source OCT, fluorescein angiography, and indocyanine green angiography performed at baseline. The characteristics of serial swept-source OCT were recorded and analyzed. RESULTS Sixty-two subjects (42 women; age: 34.2 ± 12 years) with Vogt-Koyanagi-Harada disease were included. 118 eyes (95.2%) had serous retinal detachment at presentation. 112 eyes (94.9%) showed the BLD at baseline. In 8 of 112 (7.1%) eyes with the BLD, the external limiting membrane at the anterior aspect of the BLD showed focal discontinuity. The interdigitation zone at the base of the BLD showed discontinuity in 53 of 112 (47.3%) eyes with the BLD. The ellipsoid zone could not be identified as a separate hyperreflective line at the base of the BLD in 102 of 112 eyes (91.1%). Bacillary layer detachments resolved within 3.4 ± 1.3 days after intravenous methylprednisolone therapy with improvement in the best-corrected visual acuity from 0.96 to 0.4 logarithm of the minimum angle of resolution (20/184 Snellen's equivalent) (P < 0.001). Resolution of serous retinal detachment was observed after 5.9 ± 2.6 days. CONCLUSION In eyes with acute Vogt-Koyanagi-Harada disease, the BLD is a common finding and represents a split in the photoreceptor layer at the inner segment myoid and can be differentiated from serous retinal detachment using swept-source OCT. In addition, resolution of the BLD and photoreceptor recovery can be evaluated using serial swept-source OCT.

To compare the outcomes of vitrectomy with removal of an idiopathic epiretinal membrane (ERM) in the myopic eyes with long axial length (AL) to that in the eyes with normal AL. This was a retrospective, observational, case-control study. Fifty-six eyes of 56 patients with an idiopathic ERM were studied. Twenty-eight of these eyes had an axial length longer than 26.0 mm (Group A), and the other 28 eyes had axial lengths < 26.0 mm (Group B). The age and visual acuity of the two groups were not significantly different. All subjects were treated by vitrectomy and peeling of the ERM with a 25- or 27-gauge system. The postoperative best-corrected visual acuity (BCVA) and optical coherence tomographic findings were determined at 3 and 6 months postoperatively. The mean BCVA improved from 0.35 ± 0.25 to 0.15 ± 0.25 logMAR units in the eyes with the long AL and from 0.35 ± 0.25 to 0.10 ± 0.21 logMAR units in the eyes with normal AL at 6 months postoperatively (both P < 0.001). The postoperative BCVA was not significantly different between the two groups at 6 months (P = 0.221). The central macula was thinner in the eyes of Group A than Group B (P < 0.001). The restorations of the ellipsoid zone and the external limiting membrane were observed in both groups, but the interdigitation zone was less frequently restored in Group A (P < 0.001). Vitrectomy with the removal of the epiretinal membrane is effective in attaining a good BCVA even in the myopic eyes with long AL.

Introduction: To compare the morphological and visual outcomes after pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling and flap removal to that with flap insertion in eyes with myopic macular-hole retinal detachment (MHRD). Methods: Forty-six eyes of 45 patients with MHRD were studied. Eighteen eyes were treated by PPV with ILM peeling and flap removal and 28 eyes by flap insertion, respectively. The baseline characteristics and postoperative findings were compared between the 2 groups. Results: The average age of the cases was 70.0 ± 8.5 years. The best-corrected visual acuity (BCVA) improved, from 1.51 ± 0.14 to 1.31 ± 0.20 logMAR units in the flap removal group, and from 1.20 ± 0.10 to 0.88 ± 0.10 logMAR units in the flap insertion group (p = 0.049). A significantly larger number of MHs were closed in the flap insertion group (96 vs. 50% in the removed group; p < 0.001). Restoration of the ellipsoid zone (EZ) and external limiting membrane (ELM) was also better in the flap insertion group than in the flap removal group (EZ 14 vs. 6%, p = 0.003; ELM 36 vs. 6%, p < 0.001). Discussion: The technique of ILM peeling with flap insertion is more effective in closing the MH, and results in better BCVA and better restoration of the outer retinal microstructures than flap removal.

Purpose: To investigate the reconstructive changes in foveal microstructures postoperatively and analyze the visual predictors in eyes with surgically closed traumatic macular holes (TMHs). Methods: Seventy-one eyes with TMHs that underwent vitrectomy, internal limiting membrane (ILM) peeling, and gas tamponade were reviewed. Clinical data, best-corrected visual acuity, and spectral-domain optical coherence tomography (SD-OCT) images were recorded. The length of the ellipsoid zone (EZ) defect and the integrity of postoperative external limiting membrane (ELM) were measured. Preoperative and 1-month postoperative features were analyzed, respectively, as potential predictors of visual acuity at 6 months postoperatively. Results: The primary hole closure rate was 90.14% (64/71). In 43 cases of initially closed TMHs with SD-OCT scans preoperatively and at 1 and 6 months postoperatively, the number of eyes with intact ELM increased from 18 (41.86%) at 1 month to 26 (60.47%) at 6 months ( p = 0.08), while the number of eyes with a restored EZ band remained the same in 2 eyes (4.65%). The mean length of the EZ defect progressively decreased postoperatively ( p < 0.001). Poorer preoperative visual acuity ( p = 0.002), lower mean macular hole (MH) height ( p = 0.012), and greater preoperative mean length of EZ defect ( p < 0.001) were associated with worse visual acuity 6 months postoperatively, but only the preoperative length of the EZ defect was proved to be a predictor, with the cutoff value of 1,800 μm provided by the receiver-operating characteristics (ROC) curve. Worse visual acuity and greater mean length of the EZ defect at 1 month were also associated with worse final visual acuity. Conclusions: The mean length of the EZ defect both preoperatively and 1 month postoperatively were predictors of visual outcomes at 6 months postoperatively.

To examine the influence of the inverted flap (IF) internal limiting membrane (ILM) technique in macular hole (MH) closure on outer retinal layers after MH surgery.Retrospective study. Postoperative position of ILM, recovery rate of external limiting membrane and ellipsoid zone, and best-corrected visual acuity were evaluated. The Inserted group, where the IF is placed inside the hole, was compared with the Cover group, where the IF completely covers the hole.Sixty-two eyes of 58 patients who underwent vitrectomy and ILM peeling with the IF technique for large MHs (400 µm) with successful MH closure and a follow-up of 12 months were evaluated. In the 24 eyes of the Inserted group, there was no regeneration of external limiting membrane or ellipsoid zone after 12 months. In the 38 eyes of Cover group, external limiting membrane recovered in 55.3% of patients 1 month after surgery, and in 86.1% after 12 months. The elipsoid zone layer was present in 58% of the patients.Poorer anatomical and visual results were associated with the IF technique where ILM insertion occurs compared with ILM placed over the hole. These findings suggest that insertion of the ILM in the hole might prevent outer retinal layers realignment and visual recovery in MH surgery.

PURPOSE To correlate drusen morphology and outer retinal status with autofluorescence (AF) imaging in patients with intermediate age-related macular degeneration. METHODS Drusen type and morphology were analyzed using color fundus photography and spectral-domain optic coherence tomography, whereas fundus AF was used for drusen AF evaluation. Additional structural changes on spectral-domain optic coherence tomography, such as disruption of external limiting membrane, ellipsoid zone, and retinal pigment epithelium/Bruch membrane complex, as well as the presence of choroidal hypertransmission at correspondent locations were also evaluated and correlated with fundus AF findings. Spearman's correlation coefficient was used to analyze the correlation between spectral-domain optic coherence tomography morphological characteristics of drusen and AF appearance of the corresponding drusen. Strength of correlation was calculated (r), and a P value < 0.05 was considered statistically significant. RESULTS Two hundred and twenty-eight drusen from 53 eyes of 53 patients were analyzed, 130 soft drusen (57.02%) and 98 cuticular drusen (42.98%). Sixty percent of the drusen were isoautofluorescent (n = 136), 35% hyperautofluorescent (n = 80), and 5% hypoautofluorescent (n = 12). We found positive correlation between drusen AF and hyperreflective foci (r = 0.4). Outer retinal layers morphology (external limiting membrane and ellipsoid zone status and hypertransmission) also correlates with autofluorescent findings (r = 0.3). CONCLUSION Multimodal imaging reveals a broad spectrum of ultrastructural changes, which may reflect different stages in the evolution of drusen. Our results suggest that drusen morphological characteristics and autofluorescent findings are correlated but other factors or cofactors may be involved. The described correlations will help us understand new progression biomarkers of nonexudative age-related macular degeneration.

To analyze photoreceptors’ condition after intravitreal ranibizumab treatment according to the pattern of diabetic macular edema (DME) on spectral-domain optical coherence tomography (SD-OCT). Retrospective study includes 58 treatment naive patients with DME, treated with intravitreal ranibizumab injections and followed up for at least 12 months. Patients were classified based on DME morphology on SD-OCT into: diffuse macular edema, cystoid macular edema (CME) and serous retinal detachment with CME (SRD/CME). The DME morphology was analyzed, while quantitative measurement of ellipsoid zone (EZ) defect, as well as qualitative assessment of the condition of external limiting membrane (ELM) and interdigitation zone (IZ) at foveal area, was taken before and after treatment. Before treatment, patients with CME presented worse ELM and IZ condition and greater EZ defect than patients with diffuse macular edema or SRD/CME. After treatment, the restoration of EZ defect and IZ was more evident in patients with CME than in diffuse macular edema or SRD/CME. Patients with DME presented significant photoreceptors’ restoration after intravitreal ranibizumab injections at the 12-month follow-up. The improvement in EZ defect size and IZ was dependent on the pattern of DME on SD-OCT.

BACKGROUND: To analyse cellular and spatiotemporal factors of neurodegeneration and gliosis in a patient with submacular haemorrhage (SMH) secondary to type 1 macular neovascularization in neovascular age-related macular degeneration (nAMD). METHODS: This is a case study and clinicopathologic correlation of an 84-year-old white man with nAMD treated with antiangiogenic drugs and photodynamic therapy during a 6-year follow-up. Eyes were recovered for histology 8.23 h after death. In vivo multimodal imaging including optical coherence tomography (OCT) and en face modalities was compared with ex vivo OCT and high-resolution histologic images, using a custom image registration procedure. SMH components were defined (intraretinal, subretinal, sub-retinal pigment epithelium (RPE), and dehemoglobinized blood). Neurodegenerative changes in each of these areas were described. One anonymous donor eye with haemorrhagic nAMD was also reviewed as a comparator. RESULTS: By in vivo OCT, progressive resolution of the haemorrhage and gradual transformation of sub-RPE fluid to fibrous hyperreflective tissue, progressive macular atrophy, and variation in external limiting membrane (ELM) visibility were observed. Histology showed intense photoreceptor loss with preservation and self-adhesion of macular Müller glia resulting in ELM condensation. The comparator eye exhibited shed cone inner segments among subretinal erythrocytes. CONCLUSION: This is the most detailed clinicopathologic correlation of nAMD with SMH resolution to date, and the first in the OCT era. Our results reveal profound macular neurodegeneration and gliosis, signified by condensed ELM, soon after haemorrhage begins. Intensified OCT reflectivity of the ELM, an important retinal barrier, has potential as a biomarker for severe photoreceptor loss and gliosis.

PURPOSE To describe the anatomic evolution of full-thickness macular hole closure after the inverted internal limiting membrane (ILM) flap technique. METHODS A retrospective review of 39 eyes (38 patients) with a full-thickness macular hole treated with the inverted ILM flap technique was performed. Ophthalmic examinations and imaging were performed preoperatively and postoperatively. RESULTS Macular changes in the early postoperative period included flap closure (15.4%), U-shaped closure (17.9%), V-shaped closure (33.3%), W-shaped closure (28.2%), gap closure (2.6%), and gap open (2.6%). Flap closure was associated with low myopia and shorter axial length (P < 0.05). Two types of flap closure were observed. Type 1 was characterized by gap opening with an ILM cap, followed by a thickened ILM band drawing the edges of the macular hole closer with subsequent external limiting membrane formation; Type 2 was characterized by gap closure with an ILM cap, followed by gliotic proliferation filling the gap. Flap closure configuration disappeared within 4 months postoperatively. At the last follow-up, foveal contours were U-shaped closure (25.6%), V-shaped closure (35.9%), W-shaped closure (35.9%), and gap open (2.6%). CONCLUSION Two types of flap closure were observed in the early postoperative period. Several patterns of the foveal contour were observed in the late period. The presence of the ILM flap predicts eventual hole closure. These findings require confirmation and further elucidation of their possible clinical significance.

To evaluate the structural and visual outcomes after pars plana vitrectomy (PPV) for idiopathic full-thickness macular hole (MH) with at least 5 years of follow-up information.Retrospective case series.Patients with idiopathic MH who had at least 5 years of follow-up information after PPV.Best-corrected visual acuity (BCVA) was recorded preoperatively and, when available, at 1, 2, 3, 5, 8, and 10 years after surgery. Reestablishment of the postoperative integrity of the ellipsoid zone (EZ) and the external limiting membrane (ELM) and presence of cystoid spaces were evaluated using spectral-domain (SD) OCT.Postoperative BCVA and its correlation with different SD OCT parameters.Eighty-seven eyes of 80 patients with a mean age at surgery of 68.9±7.03 years were included. The mean postoperative follow-up was 9.6±4.3 years (median, 9 years; range, 5-22 years). The mean preoperative BCVA was 0.20±0.14 (range, 0.03-0.66). Postoperative BCVA was improved at all time points compared with preoperative BCVA (P0.05). Improvement in the postoperative BCVA remained stable 10 years after surgery. Initial successful closure of MH was achieved in 82 eyes (94%). Macular hole reopening occurred in 7 eyes (8.0%). Eleven eyes (13%) were reoperated: 4 eyes (4.5%) for persistence and 7 eyes (8.0%) for reopening of MH. Indocyanine green (ICG) stain was used in 22 eyes (25.2%). Among 57 patients (66%) who were phakic before surgery, 52 eyes (91.2%) underwent cataract extraction after PPV at a mean duration of 32.7±38.5 months (range, 2-187 months). Postoperative EZ integrity was restored in 52 eyes (60%), ELM integrity was restored in 54 eyes (62%), and cystoid spaces of variable severity were observed in 28 eyes (32%). Preoperative BCVA of 20/60 or better and postoperative reestablished ELM and EZ integrity were associated significantly with better postoperative BCVA at different postoperative follow-up visits (P0.05).Visual acuity improvement after MH surgery continued during the first 3 years after PPV and was maintained thereafter in a substantial fraction of patients, and final BCVA correlated with better preoperative BCVA and better postoperative OCT parameters.

PURPOSE To evaluate the long-term results of autologous retinal pigment epithelium (RPE) and choroid transplantation (RPE-choroid patch) for exudative and atrophic maculopathies. METHODS Consecutive chart review of 120 eyes, which underwent RPE-choroid patch, from 2007 to 2017 for RPE atrophy or choroidal neovascular membrane secondary to exudative and hemorrhagic age-related macular degeneration, myopia, angioid streaks, and laser. Eyes were tested with best-corrected visual acuity (BCVA), reading ability, optical coherence tomography, fluorescein angiography and indocyanine green angiography, autofluorescence, and microperimetry. RESULTS Eighty-eight eyes of 84 patients had complete data, with 2- to 10-year follow-up. Mean age was 71.9 ± 9.06 years. Mean preoperative and postoperative BCVA was 20/320 (1.2 ± 0.2 logMAR) and 20/200 (0.94 ± 0.36 logMAR), respectively (P = 0.009). Reading ability recovered in 43% of cases. Microperimetry showed central fixation. A gain of at least 15 letters was obtained in 40% of eyes. Integrity (P = 0.009) of external limiting membrane and higher preoperative BCVA (P = 0.001) predicted better final BCVA. Complications were retinal detachment (11.4%), macular atrophy (7%), subretinal hemorrhage (4.5%), epiretinal membrane (4.5%), recurrent choroidal neovascular membrane (4.5%), macular hole (3.4%), and cystoid edema (3%). CONCLUSION Autologous RPE-choroid patch achieved long-lasting BCVA improvement and central fixation, in eyes with choroidal neovascular membrane and intact external limiting membrane. Atrophic maculopathies only obtained temporary visual benefit.

Aim To describe a novel OCT finding called "Plume sign" in macular cysts. Methods Case records of five cases were retrospectively reviewed. Their case history and imaging findings on spectral domain optical coherence tomography (SD-OCT, Spectralis, Heidelberg, Germany) have been described. Results We observed five cases which had a solitary cyst foveal or parafoveal in location, was unique due to the presence of a plume-shaped internal substance, was treated with topical NSAIDs and was associated with good visual outcomes. We observed three cardinal events; firstly, retinal thickening followed by the formation of a foveal or parafoveal solitary cyst. Secondly, a vertical expansion of the solitary cysts in an inverted flask-shaped configuration associated with splitting of the retinal layers suggested by a hyper-reflective line and/or a hyporeflective cleft in the outer nuclear layer. Thirdly and finally, a breach of the outer retina with involvement of the external limiting membrane (ELM) and ellipsoid zone (EZ) with an exit trail of proteinaceous material through the defect in the shape of a plume of smoke hyper-reflective on OCT followed by deturgescence of the cyst. Conclusion In conclusion, we describe the "plume" sign - a novel OCT finding is cysts and provide a possible pathogenic hypothesis.

Purpose To describe a novel spectral-domain (SD) OCT finding of a double-layer sign at the site of activity in tubercular serpiginous-like choroiditis (SLC) and how this sign can be used to assess treatment response in these eyes. Design Retrospective, observational case series. Methods We retrospectively reviewed simultaneous fundus photographs and SD OCT and fundus autofluorescence (FAF) images of eyes affected with tubercular SLC from the acute stage until resolution of lesions using the Heidelberg Spectralis HRA and OCT system (Heidelberg Engineering, Heidelberg, Germany). Main Outcome Measures Occurence of the double layer sign (DLS) during activity; reduction in the double layer sign (DLS) with resolution of choroidal and retinal inflammation; correlation of SD OCT and FAF findings. Results Five eyes of 5 patients were studied in detail. Spectral-domain OCT findings included choroidal elevation and a double-layer sign (separation of hyperreflective retinal pigment epithelium [RPE] from Bruch’s membrane, with the gap between them showing moderate reflectivity) at the site of activity. This correlated with hyperautofluorescence with indistinct borders on FAF imaging. Reduction in the double-layer sign became evident as the lesions began to resolve, and eventually this area was replaced by hyperreflective, irregular, knobbly elevations of the RPE. In eyes with severe inflammation and increased choroidal elevation on OCT, the double-layer sign was very prominent. As the choroidal elevation decreased on OCT, increased reflectance from the choroidal layers was evident. As the lesions resolved, the lesions became predominantly hypoautofluorescent on FAF and loss of RPE, ellipsoid zone, and external limiting membrane on SD OCT scan became evident. Good correlation was found between the resolution of the double-layer sign on SD OCT and FAF findings. Conclusions The double-layer sign on SD OCT may be a useful finding in monitoring the activity in tubercular SLC. The OCT changes can be correlated with FAF imaging in these eyes.

Introduction Subthreshold micropulse laser treatment with a 532 nm (532-SML) wavelength has been suggested as a treatment option for the treatment of chronic central serous retinopathy (cCSR). The objective is to present its effects and complications. Methods We present a retrospective cohort study of cCSR patients submitted to 532-SML. Best-corrected visual acuity (BCVA) and spectral-domain optical coherence tomography (SD-OCT) parameters - central macular thickness, subfoveal outer nuclear layer, external limiting membrane, ellipsoid band, interdigitation band, subretinal fluid and choroidal thickness - were evaluated before and 12 weeks after treatment. A power of 50%, a duty cycle of 5%, exposure time of 200 ms and a spot size of 160 µm were the applied laser parameters. Results We included 26 eyes. Overall there were no significant changes in visual acuity (median 0.20 (IQR 0) logMAR before and after treatment) or SD-OCT parameters. However, visual benefits occurred in 42.3% (n=11) of the patients and in half of the cases, subretinal fluid was completely reabsorbed. There were no complications. Conclusion In this study, 532-SML was overall ineffective on cCSR as it did not lead to significant changes in the overall median visual acuity and SD-OCT parameters. However, some patients may have benefited functionally and anatomically from the treatment; further investigation is necessary to understand the potential of 532-SML.

The purpose of the study is to evaluate the heritability of inner retinal layer (IRL) and outer retinal layer (ORL) thicknesses in the healthy Korean population. This was a cross-sectional, twin and family study. We included 374 Korean adults with healthy eyes from 89 families. IRL thickness (from the internal limiting membrane to the external limiting membrane) and ORL thickness (from the external limiting membrane to the outer border of the retinal pigment epithelium layer) were measured in the nine macular subfields as defined by the Early Treatment of Diabetic Retinopathy Study using optical coherence tomography. The heritability on IRL and ORL thicknesses were investigated using a variance decomposition model. The heritability of IRL thickness was 0.87, 0.58, 0.85, 0.89, and 0.74 for the central, inner superior, inner inferior, inner temporal, inner nasal subfields, respectively; and 0.62, 0.83, 0.62, and 0.60 for the outer superior, outer inferior, outer temporal, outer nasal subfields, respectively. The heritability of ORL thickness was 0.56, 0.75, 0.66, 0.72, and 0.56 for the central, inner superior, inner inferior, inner temporal, inner nasal subfields, respectively; and 0.64, 0.63, 0.73, 0.54 for the outer superior, outer inferior, outer temporal, and outer nasal subfields, respectively. The heritability estimates of IRL thickness and ORL thickness ranged from moderate to high. The IRL thickness at the central, inner temporal, and inner inferior subfields had particularly high heritability.

Purpose: To describe changes in blue-light fundus autofluorescence (FAF) and corresponding alterations in optical coherence tomography (OCT) within the irradiation field after ruthenium-106 brachytherapy (RBT) for choroidal melanoma. Methods: Consecutive patients with choroidal melanoma were included in a retrospective case series. Patients were treated with RBT at a single institution. As part of their routine examination patients underwent multimodal imaging including ultrasonography, fundus photography, OCT, and FAF imaging (excitation = 488 nm). FAF images were analysed for changes within the irradiation field. Results: 31 patients (mean age 65.7 years) were treated with RBT for unilateral choroidal melanoma. Mean tumour height before therapy was 2.7 mm (SD 1.0). Mean follow-up time was 23.3 months (SD 13.3). Main FAF characteristics attributable to RBT emerged as increased FAF with speckled decreased FAF (FAF mottling) within the irradiation field and a rim of increased FAF at its border. OCT scans demonstrated loss of the ellipsoid zone and the external limiting membrane, thinning of the neurosensory retina, and alterations of the retinal pigment epithelium like clumping, migration, and atrophy. Conclusions: FAF changes in the irradiation field after RBT of choroidal melanomas follow a characteristic pattern that correlates with distinct OCT alterations. FAF and OCT imaging give additional information to monitor effects of RBT and, therefore, complement multimodal imaging techniques after plaque therapy.

Objective: To investigate the influence of the inverted flap technique compared with traditional internal limiting membrane (ILM) peeling in the postoperative remodelling of outer retinal layers of idiopathic macular holes (MHs) >450 µm. Methods: We analyzed medical records and imaging studies of all patients with an idiopathic MH >450 µm who underwent vitrectomy at the Sacco University Hospital, Milan, and the Sacro Cuore Don Calabria Hospital, Verona, Italy, between January 2008 and December 2017. Out of 41 eyes evaluated, 17 were treated with traditional ILM peeling and 24 with the inverted ILM flap technique. All patients underwent follow-up examinations every 3 months and all of them completed a final visit 12 months after surgery. Best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) parameters were evaluated at each visit. The main outcome measures were the postoperative recovery rate of the external limiting membrane (ELM) and ellipsoid zone (EZ), and postoperative BCVA. Correlations between OCT measurements and visual outcome were analyzed. Results: The ELM recovery rate in the ILM peeling group (15/17 eyes, 88%) was higher than in the ILM flap group (14/24 eyes, 58%) (p = 0.079). The EZ recovery rate was similar in the 2 groups, 7/17 eyes (41%) in the ILM peeling and 8/24 eyes (33%) in the ILM flap group (p = 0.744). Eyes without a persistent hyper-reflective “plug” at the edges of the MH showed a significantly higher EZ recovery rate (11/18, 61%) compared with eyes showing a persistent plug (4/23, 17%) (p = 0.008). The mean BCVA improved significantly in both groups: from 0.93 logMAR (20/170) to 0.26 logMAR (20/36) in the ILM peeling and from 0.98 logMAR (20/190) to 0.37 logMAR (20/46) in the ILM flap group. The final BCVA tended to be better in the ILM peeling group (p = 0.085). Conclusions: Given the limited information about the influence of ILM flap versus traditional ILM peeling in the postoperative remodelling of large idiopathic MHs, our data provides some new insights into the healing process of MHs >450 µm. This should be considered as part of the decision process about whether to perform an ILM flap in these patients.

PurposeTo evaluate spectral-domain (SD)-OCT features associated with baseline vision and visual outcomes in the prospective, multicenter Study Evaluating Dosing Regimens for Treatment with Intravitreal Ranibizumab Injections in Subjects with Macular Edema following Retinal Vein Occlusion (SHORE).DesignPost hoc analysis of prospective clinical trial data.ParticipantsTwo hundred two participants in the 15-month, phase 4 SHORE study comparing monthly versus pro re nata ranibizumab after 7 monthly doses in eyes with retinal vein occlusion (RVO) with macular edema.MethodsBaseline SD-OCT images were assessed for (1) central subfield thickness (CST); (2) presence of vitreomacular adhesion, vitreomacular traction, or epiretinal membrane; (3) presence, location, and amount of intraretinal fluid or subretinal fluid (SRF); (4) presence, location, and amount of hyperreflective foci (HF); (5) disorganization of retinal inner layers (DRIL); and (6) disruption of external limiting membrane (ELM), ellipsoid zone (EZ), and interdigitation zone (IZ). Univariate and multivariate regression analyses were performed to evaluate the association of these features with baseline best-corrected visual acuity (BCVA) and change in BCVA after 7 monthly ranibizumab injections.Main outcome measuresAssociation of SD-OCT features with baseline BCVA and change in BCVA after 7 monthly ranibizumab injections.ResultsBefore therapy, worse baseline BCVA was associated with ERM presence (P= 0.0045), thicker SRF (P= 0.0006), larger intraretinal cysts (P= 0.0015), and higher percentage of DRIL (P < 0.0001), percentage of ELM disruption (P < 0.0001), percentage of EZ disruption (P= 0.0003), and percentage of IZ disruption (P= 0.0018). In multivariate models, only percentage of ELM disruption independently impacted baseline BCVA (P < 0.0001). After 7 monthly ranibizumab injections, mean BCVA improved by 18.3±12.6 Early Treatment Diabetic Retinopathy Study letters in treated eyes. The only factors independently associated with BCVA gain after 7 monthly ranibizumab treatments were younger age (P < 0.0001) and worse baseline BCVA (P < 0.0001).ConclusionsAlthough SD-OCT features may be associated with presenting vision in eyes with macular edema and RVO, most eyes treated with ranibizumab achieve substantial vision gains, and only older age and better baseline BCVA limited visual improvements.

To investigate the role of an internal limiting membrane (ILM) flap in macular hole (MH) surgery on closure rate, visual acuity, and integrity of the outer retinal layers.Retrospective, nonrandomized interventional analysis in which 117 eyes of 117 patients were included who had undergone pars-plana vitrectomy (PPV) and gas tamponade for primary idiopathic MH400 µm with either conventional ILM peeling or with inverted ILM flap technique at The Royal Liverpool University Hospital between January 2016 and April 2018. Main outcome measures were closure of MH, best-corrected visual acuity (BCVA) at 3, 6, and 12 months, and restoration of external limiting membrane and ellipsoid zone (EZ) using optical coherence tomography.Macular hole closure rate was significantly higher in patients with an ILM flap (67/68; 98.53%) than in those with conventional ILM peeling (43/49; 87.76%) (P = 0.02). Both groups showed significant improvements in their preoperative to postoperative BCVA at 3 months from 1.07 (0.43) logarithm of the minimum angle of resolution (logMAR) (20/235 Snellen) to 0.71 (0.34) logMAR (20/103 Snellen) (P0.001), but there was no significant difference between the two groups (P = 0.45, P = 0.71). We found significant associations between postoperative BCVA and preoperative BCVA (P0.01) and the integrity of the EZ (P0.01). In 35 patients who had follow-up to 12 months, there was a significant improvement in BCVA between 3, 6, and 12 months from 0.73 (0.45) logMAR (20/107 Snellen) to 0.53 (0.24) logMAR (20/68 Snellen) and to 0.35 (0.18) logMAR (20/45 Snellen), respectively (P0.01). There was no significant difference at these time periods between the two groups (P = 0.62, P = 0.21, P = 0.31). The integrity of the EZ also improved significantly between 3, 6, and 12 months (P = 0.01), irrespective of the presence of an ILM flap (P = 0.58), but with a trend toward delay in restoration in those patients with an ILM flap. The improvement in BCVA at 12 months, taking into account the age of the patient, size and duration of the MH, presence of an ILM flap, and preoperative BCVA was dependent on the state of the EZ (P = 0.01).In patients undergoing primary pars-plana vitrectomy for MH400 µm, the presence of an inverted ILM flap was associated with a significantly higher closure rate than a conventional ILM peeling. Best-corrected visual acuity showed a strong correlation with the integrity of the EZ and both improved significantly between 3, 6, and 12 months, irrespective of the presence of an ILM flap.