Alternative Tissue Fixation Protocols Dramatically Reduce the Impact of DNA Artifacts, Unraveling the Interpretation of Clinical Comprehensive Genomic Profiling.

Formalin-fixed paraffin-embedded (FFPE) samples represent the cornerstone of tissue-based analysis in precision medicine. Targeted next-generation sequencing panels are routinely used to analyze a limited number of genes to guide treatment decision-making for advanced-stage patients. The number and complexity of genetic alterations to be investigated are rapidly growing; in several instances, a comprehensive genomic profiling analysis is needed. The poor quality of genetic material extracted from FFPE samples may impact the feasibility/reliability of sequencing data. We sampled 9 colorectal cancers to allow 4 parallel fixations: (1) neutral buffered formalin (NBF), (2) acid-deprived formalin fixation (ADF), (3) precooled ADF (coldADF), and (4) glyoxal acid free (GAF). DNA extraction, fragmentation analysis, and sequencing by 2 large next-generation sequencing panels (OCAv3 and TSO500) followed. We comprehensively analyzed library and sequencing quality controls and the quality of sequencing results. Libraries from coldADF samples showed significantly longer reads than the others with both panels. ADF-derived and coldADF-derived libraries showed the lowest level of noise and the highest levels of uniformity with the OCAv3 panel, followed by GAF and NBF samples. The data uniformity was confirmed by the TSO500 results, which also highlighted the best performance in terms of the total region sequenced for the ADF and coldADF samples. NBF samples had a significantly smaller region sequenced and displayed a significantly lower number of evaluable microsatellite loci and a significant increase in single-nucleotide variations compared with other protocols. Mutational signature 1 (aging and FFPE artifact related) showed the highest (37%) and lowest (17%) values in the NBF and coldADF samples, respectively. Most of the identified genetic alterations were shared by all samples in each lesion. Five genes showed a different mutational status across samples and/or panels: 4 discordant results involved NBF samples. In conclusion, acid-deprived fixatives (GAF and ADF) guarantee the highest DNA preservation/sequencing performance, thus allowing more complex molecular profiling of tissue samples.

Apoptosis in mesenchymal stromal cells activates an immunosuppressive secretome predicting clinical response in Crohn's disease.

In vivo apoptosis of human mesenchymal stromal cells (MSCs) plays a critical role in delivering immunomodulation. Yet, caspase activity not only mediates the dying process but also death-independent functions that may shape the immunogenicity of apoptotic cells. Therefore, a better characterization of the immunological profile of apoptotic MSCs (ApoMSCs) could shed light on their mechanistic action and therapeutic applications. We analyzed the transcriptomes of MSCs undergoing apoptosis and identified several immunomodulatory factors and chemokines dependent on caspase activation following Fas stimulation. The ApoMSC secretome inhibited human T cell proliferation and activation, and chemoattracted monocytes in vitro. Both immunomodulatory activities were dependent on the cyclooxygenase2 (COX2)/prostaglandin E2 (PGE2) axis. To assess the clinical relevance of ApoMSC signature, we used the peripheral blood mononuclear cells (PBMCs) from a cohort of fistulizing Crohn's disease (CD) patients who had undergone MSC treatment (ADMIRE-CD). Compared with healthy donors, MSCs exposed to patients' PBMCs underwent apoptosis and released PGE2 in a caspase-dependent manner. Both PGE2 and apoptosis were significantly associated with clinical responses to MSCs. Our findings identify a new mechanism whereby caspase activation delivers ApoMSC immunosuppression. Remarkably, such molecular signatures could implicate translational tools for predicting patients' clinical responses to MSC therapy in CD.

MULTIMODAL IMAGING CHARACTERISTICS AND FUNCTIONAL CORRELATES IN RIP HEALING.

PURPOSE: To report the imaging and functional features of the repair tissue following retinal pigment epithelium (RPE) tears. METHODS: This cross-sectional observational study included patients with RPE tears secondary to neovascular age-related macular degeneration and at least 12 months of follow-up. The following variables were analyzed: best-corrected visual acuity; retinal sensitivity using microperimetry; outer retinal layers status and RPE resurfacing on optical coherence tomography; fibrosis; autofluorescence signal recovery using blue-light and near-infrared autofluorescence. RESULTS: Overall, 48 eyes were included (age: 82 ± 5 years) and 34 of them showed signs of healing. Retinal pigment epithelium resurfacing was noticed in 22 cases, whereas fibrosis appeared in 21 eyes. Autofluorescence improved in 17 cases using blue-light infrared autofluorescence and 7 eyes on near-infrared autofluorescence. Outer retinal layers were more frequently preserved when RPE resurfacing and autofluorescence improvement occurred ( P < 0.05). Although best-corrected visual acuity was higher for smaller RPE tears ( P = 0.01), retinal sensitivity of the healing tissue was positively affected by autofluorescence improvement ( P < 0.001) and by absence of fibrosis ( P = 0.03). CONCLUSION: Autofluorescence signal recovery after rip occurrence possibly reflects the underlying status of the RPE and is associated with better functional outcomes. Our findings highlight the importance of blue-light infrared autofluorescence and especially near-infrared autofluorescence assessment in the setting of rip healing.

Identification of altered biological processes in heterogeneous RNA-sequencing data by discretization of expression profiles.

Heterogeneity is a fundamental feature of complex phenotypes. So far, genomic screenings have profiled thousands of samples providing insights into the transcriptome of the cell. However, disentangling the heterogeneity of these transcriptomic Big Data to identify defective biological processes remains challenging. Here we present GSECA, a method exploiting the bimodal behavior of RNA-sequencing gene expression profiles to identify altered gene sets in heterogeneous patient cohorts. Using simulated and experimental RNA-sequencing data sets, we show that GSECA provides higher performances than other available algorithms in detecting truly altered biological processes in large cohorts. Applied to 5941 samples from 14 different cancer types, GSECA correctly identified the alteration of the PI3K/AKT signaling pathway driven by the somatic loss of PTEN and verified the emerging role of PTEN in modulating immune-related processes. In particular, we showed that, in prostate cancer, PTEN loss appears to establish an immunosuppressive tumor microenvironment through the activation of STAT3, and low PTEN expression levels have a detrimental impact on patient disease-free survival. GSECA is available at https://github.com/matteocereda/GSECA.

Intravitreal injection associated rhegmatogenous retinal detachment: outcomes of a European analysis.

PURPOSE: As the number of intravitreal injections (IVI) increases annually, this study aimed to assess the anatomical and functional outcomes following rhegmatogenous retinal detachment (RRD) surgery for IVI-associated RRD (IVARD). METHODS: All non-vitrectomized eyes developing IVARD since 2007 in two European vitreoretinal centers (Department of Ophthalmology, LMU Munich, Germany, and Eye Clinic Luigi Sacco, University of Milan, Milan, Italy) were included. Main outcomes were primary and secondary retinal attachment rate after surgery, rate of proliferative vitreoretinopathy (PVR), and final functional result. Ten years of incidence rates per injection were calculated for one center. RESULTS: Fifty-two eyes of 52 patients comprised the study. Primary anatomic success rate was 83% (n = 43) and secondary 96% (n = 50). PVR was observed in all uveitic eyes (n = 3), in eyes with postoperative cystoid macular edema (n = 2), and in 8 of 9 eyes that received the dexamethasone implant (DEX). Age, number of prior injections, duration of symptoms, or time between last IVI and RRD did not show any statistically significant differences with regard to presence of PVR or not. Mean BCVA improved in 28 cases, remained stable in 16 cases, and worsened in 8 cases. The RRD incidence rate was statistically significant higher for DEX and ocriplasmin compared with that for anti-VEGF agents. CONCLUSION: The anatomical result after one surgical intervention seems acceptable, but the final visual outcome remains rather poor, because of the underlying macular disease. In our population, injection with DEX is associated with higher IVARD rate, presence and development of PVR, and recurrent RRD in comparison with anti-VEGF agents.

Sutureless scleral fixation: comparison between 3-piece IOL and new single-piece foldable IOL.

PURPOSE: Comparing two different sutureless scleral fixation techniques. METHODS: A retrospective study of patients who underwent sutureless scleral fixation IOL from October 2013 to May 2018 at "Luigi Sacco Hospital", University of Milan. Comparison between two groups: Group 1 implanted with a 3-piece ALCON-MA60AC and group 2 implanted with a newly developed single-piece foldable IOL SOLEKO FIL-SSF. Patients underwent a complete preoperative ophthalmic assessment and post-operative evaluation at 1, 3, and 6 months. Vitrectomy was performed in all cases. The two groups were compared for age, axial length, and lens status at baseline. Visual acuity, refractive results, surgical time, and post-operative complications were recorded. RESULTS: Thirty-one eyes were included: group 1, 15 eyes of 15 patients, and group 2, 16 eyes of 14 patients. No difference was found in visual acuity. Mean refractive error was 1D in both groups (group 1 1.01D, group 2 1.09D), but spherical equivalent was more often moved toward negative values and induced astigmatism was greater in the 3-piece group (group 1 1.91D [SD ± 2.07], group 2 0.67D [SD ± 0.88] P = 0.04). Surgical procedure was faster in group 2 (mean time difference 21', P = 0.01*). New displacement occurred in 5 cases (33%) of group 1 and in no cases of group 2 (P = 0.01*). Post-operative bleeding was registered only in group 1 (20%), but the difference was not statistically significant. CONCLUSIONS: The group 2 IOL gives in our sample better results due to less post-operative astigmatism and reducing dislocation and bleeding during follow-up. Surgical technique appeared easier and faster: the specifically designed IOL seems to be a feasible solution for sutureless scleral fixation.

Artificial Intelligence in Bulk and Single-Cell RNA-Sequencing Data to Foster Precision Oncology.

Artificial intelligence, or the discipline of developing computational algorithms able to perform tasks that requires human intelligence, offers the opportunity to improve our idea and delivery of precision medicine. Here, we provide an overview of artificial intelligence approaches for the analysis of large-scale RNA-sequencing datasets in cancer. We present the major solutions to disentangle inter- and intra-tumor heterogeneity of transcriptome profiles for an effective improvement of patient management. We outline the contributions of learning algorithms to the needs of cancer genomics, from identifying rare cancer subtypes to personalizing therapeutic treatments.

Omic approaches to pediatric bone sarcomas.

Over the last decade, next-generation sequencing technologies have improved our ability to assess biological aspects, at genomic and transcriptomic levels, on a large scale- and have been increasingly used for the management of adult cancers. However, their efficacy and feasibility within pediatrics is still under investigation. "Omic" approaches represent an opportunity to understand the oncogenic mechanisms driving the onset and progression of bone sarcoma and improve the clinical management of young patients with bone sarcomas. This review focuses on the current genomic and transcriptomic characteristics of managing pediatric patients, affected by Ewing sarcoma and osteosarcoma.

Large Idiopathic Macular Hole Surgery: Remodelling of Outer Retinal Layers after Traditional Internal Limiting Membrane Peeling or Inverted Flap Technique.

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.

Foveal Abnormality associated with epiretinal Tissue of medium reflectivity and Increased blue-light fundus Autofluorescence Signal (FATIAS).

PURPOSE: To describe a distinct vitreomacular interface disorder (VMID) termed Foveal Abnormality associated with epiretinal Tissue of medium reflectivity and Increased blue-light fundus Autofluorescence Signal (FATIAS). METHODS: A case series including forty-seven eyes of 47 patients. The included eyes must present an irregular foveal contour on optical coherence tomography (OCT) and a pathologically increased autofluorescent signal at the fovea on blue-light fundus autofluorescence (B-FAF). Main outcome measures were morphologic characteristics of the lesions, logarithm of minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA), and central foveal thickness (CFT). RESULTS: The following two types of FATIAS were identified: (1) the step type characterized by an asymmetric contour of the foveal pit and by a tissue of medium reflectivity on the foveal surface and (2) the rail type characterized by a shallow foveal pit and a rail of tissue of medium reflectivity on the foveal surface. The outer retinal bands were continuous in all cases. Both types presented with an area of increased B-FAF signal, usually bilobed in the step type and round and centered on the foveal pit in the rail type. LogMAR BCVA was 0.09 ± 0.1 and 0.1 ± 0.1 (P = 0.91), and CFT was 197.8 ± 9.7 and 202.2 ± 13.2 (P = 0.19) in the step and in the rail group, respectively. CONCLUSIONS: We describe a distinct VMID named FATIAS. Two types of FATIAS may be appreciated with SD-OCT and B-FAF analyses, the step and the rail type. Both are characterized by abnormal foveal contour and autofluorescence signal.

OPTICAL COHERENCE TOMOGRAPHY 2: Diagnostic Tool to Study Peripheral Vitreoretinal Pathologies.

PURPOSE: To investigate the utility of new wide-field optical coherence tomography (OCT) device in the evaluation of mid and far retinal periphery and to show its feasibility and advantages in clinical practice. METHODS: Consecutive patients underwent a complete ophthalmologic examination including standard OCT and new prototype OCT2 derived from Heidelberg Spectralis. RESULTS: Thirty-one eyes of 31 patients were studied with a total of 44 lesions, including 18 retinal detachments, 15 retinal holes and tears, 9 retinoschisis, and 2 retinal tufts. Fourteen (32%) lesions were found in mid and 30 (68%) in far periphery with 9 (20%) lesions in the superior region, 10 (23%) in the superior temporal, 8 (18%) in the temporal, 4 (9%) in the inferior temporal, 7 (16%) in the inferior, 4 (9%) in the nasal, and 2 (5%) in the superior nasal. Among the lesions evaluated by OCT2, 10 (71%) in mid periphery and 11 (37%) in far periphery could be imaged by standard OCT. CONCLUSION: The introduction of OCT2 into clinical practice may provide significant benefits for imaging peripheral retinal disorders. The application of OCT2 technology with 55° lens and scan length and angle modulation could improve our understanding of peripheral vitreoretinal disorders and facilitate their management.

SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN CHOROIDAL MELANOMA: An Analysis of 22 Consecutive Cases.

PURPOSE: To describe the imaging features of choroidal melanoma using swept-source optical coherence tomography angiography (SS-OCT-A) and to evaluate its ability to display tumor intrinsic vasculature. METHODS: Consecutive patients diagnosed with choroidal melanoma underwent a complete ophthalmic evaluation, including best-corrected visual acuity, color fundus photography, B-scan ultrasound, fluorescein angiography, indocyanine green angiography, and SS-OCT-A (PLEX Elite 9000; Carl Zeiss Meditec, Inc, Dublin, CA). RESULTS: Twenty-two eyes of 22 consecutive patients were included in the study; 11 cases (50%) were treatment naive. Three lesions (14%) were located at the macula, 14 (63%) between the macula and equator, and 5 (23%) between the equator and the ora serrata. The mean tumor base and thickness were, respectively, 10.3 mm (range 5-15 mm) and 4.3 mm (range 1.5-8.9 mm). Seventeen lesions (77%) were dome shaped, whereas 5 (23%) had a mushroom configuration. Thirteen lesions (59%) were pigmented, 5 (23%) partially pigmented, and 4 (18%) amelanotic. An exudative retinal detachment was documented in 13 eyes (59%). Fluorescein angiography and indocyanine green angiography were performed in 20 patients and disclosed intrinsic microvasculature of the tumor, respectively, in 4 (20%) and 20 (100%) cases. Swept-source optical coherence tomography angiography was performed in 22 eyes and detected microvasculature of choroidal melanoma in all cases. Specifically, intrinsic vasculature could be recognized in 14 eyes (64%) using the automated choroid segmentation, 16 eyes (73%) using the automated whole eye segmentation, and in 22 eyes (100%) with fine manual adjustments of segmentation lines. CONCLUSION: Swept-source optical coherence tomography angiography represents a valid imaging technique to evaluate patients affected by choroidal melanomas. In our series, SS-OCT-A disclosed the intrinsic microvasculature of the tumor in all cases despite their size, location, and history of previous treatments.

A Comprehensive Bioinformatics Analysis of UBE2C in Cancers.

Ubiquitination is one of the main post-translational modification of proteins. It plays key roles in a broad range of cellular functions, including protein degradation, protein interactions, and subcellular location. In the ubiquitination system, different proteins are involved and their dysregulation can lead to various human diseases, including cancers. By using data available from the Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases, we here show that the ubiquitin conjugating enzyme, E2C (UBE2C), is overexpressed in all 27 cancers we investigated. UBE2C expression is significantly higher in late-stage tumors, which might indicate its involvement in tumor progression and invasion. This study also revealed that patients with higher UBE2C levels showed a shorter overall survival (OS) time and worse OS prognosis. Moreover, our data show that UBE2C higher-expression leads to worse disease-free survival prognosis (DFS), indicating that UBE2C overexpression correlates with poor clinical outcomes. We also identified genes with positive correlations with UBE2C in several cancers. We found a number of poorly studied genes (family with sequence similarity 72-member D, FAM72D; meiotic nuclear divisions 1, MND1; mitochondrial fission regulator 2, MTFR2; and POC1 centriolar protein A, POC1A) whose expression correlates with UBE2C. These genes might be considered as new targets for cancers therapies since they showed overexpression in several cancers and correlate with worse OS prognosis.

MEGA-V: detection of variant gene sets in patient cohorts.

Summary: : Detecting significant associations between genetic variants and disease may prove particularly challenging when the variants are rare in the population and/or act together with other variants to cause the disease. We have developed a statistical framework named Mutation Enrichment Gene set Analysis of Variants (MEGA-V) that specifically detects the enrichments of genetic alterations within a process in a cohort of interest. By focusing on the mutations of several genes contributing to the same function rather than on those affecting a single gene, MEGA-V increases the power to detect statistically significant associations. Availability and Implementation: MEGA-V is available at https://github.com/ciccalab/MEGA. Contact: francesca.ciccarelli@kcl.ac.uk. Supplementary information: Supplementary data are available at Bioinformatics online.

Vitrectomy for optic disc pit maculopathy: a long-term follow-up study.

PURPOSE: To evaluate the clinical outcomes of vitrectomy with induction of posterior vitreous detachment for the treatment of optic disc pit maculopathy. METHODS: We retrospectively evaluated medical records and imaging studies of 11 consecutive patients with optic disc pit maculopathy who underwent vitrectomy at Sacco University Hospital, Milan, Italy, between October 2008 and December 2015. Induction of a posterior vitreous detachment (PVD) was the aim of our surgery. Intravitreal injection of ocriplasmin (Jetrea, Thrombogenics USA, Alcon/Novartis EU) was performed before surgery in three eyes of very young patients. Gas tamponade (sulfur hexafluoride (SF6) 20%) was used only in the first five cases. Main outcome measures were anatomic results as determined by optical coherence tomography and postoperative best-corrected visual acuity (BCVA). RESULTS: Before surgery, a macular detachment was present in 10 eyes and a lamellar hole of the outer retina was detected in 9 eyes. Intraoperatively, two iatrogenic paramacular holes developed in two patients during posterior hyaloid dissection. Time to PVD induction appeared to be greatly reduced in the three patients injected with ocriplasmin before surgery. Patients were followed up for a mean of 38 months (range, 18-84) after surgery. Postoperatively, one patient (9%) developed a retinal detachment that was repaired with one additional vitrectomy. Complete resolution of fluid in and under the fovea was achieved in 8 of the remaining 10 eyes (80%) without additional treatment. Reduction of the inner retinal fluid always preceded the decrease of outer retinal fluid, which in turn anticipated the absorption of macular detachment. The macular detachment resolved in a mean of 14 months after surgery. Postoperative BCVA (mean, 0.63) improved significantly compared with preoperative BCVA (mean, 0.27) (P = 0.005). Nine eyes (82%) had a postoperative BCVA of 0.5 or better. CONCLUSION: Vitrectomy with induction of PVD is a safe and successful therapeutic option for the treatment of optic disc pit maculopathy. The adjunct of ocriplasmin might facilitate the induction of PVD and reduce the risk of iatrogenic retinal holes.

SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY FINDINGS IN ENDOGENOUS CANDIDA ENDOPHTHALMITIS AND THEIR CLINICAL RELEVANCE.

PURPOSE: To describe vitreal, retinal, and choroidal features of eyes affected by Endogenous candida endophthalmitis (ECE) analyzed by spectral domain optical coherence tomography (SD-OCT) and to evaluate their clinical impact. METHODS: Medical records and SD-OCT images from eyes diagnosed with ECE at four retina and uveitis tertiary referral centers were retrospectively evaluated. Spectral domain optical coherence tomography images were analyzed to evaluate the structural changes occurring in the vitreous, the retina, and the choroid in areas involved by ECE. Baseline and final best-corrected visual acuity were correlated with SD-OCT findings. RESULTS: Fifteen eyes from nine patients were enrolled. Vitreous involvement (vitreous cells, posterior hyaloid thickening) was detected in 13/15 eyes. Peculiar hyper-reflective preretinal aggregates obscuring the underlying retina because of a shadowing effect ("rain-cloud" sign) were noticed in all eyes with vitreous involvement. Two patterns of retinal and choroidal findings were identified: the first (six eyes) confined within the inner retinal layers (Intraretinal Pattern), the second (nine eyes) involving both retina (full thickness) and choriocapillaris (Chorioretinal Pattern). None of the eyes showed both patterns. None of the eyes, regardless the pattern, showed choroidal thickening. Baseline best-corrected visual acuity was not associated with OCT pattern (P = 0.09). On the contrary, final best-corrected visual acuity was significantly higher in patients showing Intraretinal Pattern (∼20/25, 0.06 ± 0.08 LogMAR) than in subjects with Chorioretinal Pattern (∼20/50, 0.44 ± 0.30 LogMAR) (P = 0.01). CONCLUSION: Endogenous candida endophthalmitis showed peculiar features on SD-OCT. Two distinct patterns of chorioretinal involvement influencing the final best-corrected visual acuity were identified. Spectral domain optical coherence tomography could be useful in the diagnosis, management, and outcome prediction in ECE.

OCRIPLASMIN FOR VITREOMACULAR TRACTION: LOOKING OUTSIDE THE MACULA: A Wide-Field Optical Coherence Tomography Study.

PURPOSE: To evaluate baseline features and morphologic changes of vitreoretinal adhesion and outer retinal layers outside the macula after intravitreal ocriplasmin injection. To study the relation between vitreous detachment and attenuation of retinal outer segments signal. METHODS: Retrospective cases series of 15 eyes. Each eye was scanned with the 55° wide-field optical coherence tomography lens in 6 different locations, three horizontal B-scan (central, temporal, and nasal) and three vertical B-scan (central, superior, and inferior) at baseline, 1 week, 1 month, 3 months, and 6 months after injection. RESULTS: After ocriplasmin injection, vitreomacular traction (VMT) resolved in 12 patients (80%), 3 of them presenting a complete posterior vitreous detachment. Eight patients (53%) showed a panretinal attenuation of photoreceptors outer segment signal, 7 with VMT resolution and 1 with non-posterior vitreous detachment and no VMT resolution. In three patients after VMT resolution the attenuation involved also areas with no posterior vitreous detachment. The attenuation resolved during follow-up in 7/8 eyes (87.5%). CONCLUSION: Intravitreal ocriplasmin injection induced resolution of VMT in most cases and more rarely a release of vitreopapillary adhesion and a complete posterior vitreous detachment. An acute panretinopathy was visible in more than half of the patients and was not related to vitreous detachment.

Imaging of tangential traction types in lamellar macular holes.

PURPOSE: To determine the best imaging procedure for the definition of tangential tractions generated by epiretinal membranes in lamellar macular holes. METHODS: Inclusion criteria were a diagnosis of lamellar macular hole with tractional epiretinal membranes based upon fundus autofluorescence (FAF), and spectral-domain optical coherence tomography (SD-OCT) imaging (HRA + OCT Spectralis, Heidelberg Engineering, Heidelberg, Germany). Tangential tractions were evaluated with infrared reflectance (IR; 820 nm) and OCT en face (193 B-scans, 30 × 20°pattern size, 31 µm between two consecutive B-scans). Three different categories of tangential traction were previously defined: 1) unidirectional, 2) pluridirectional, and 3) concentric. Two independent masked physicians evaluated the images in order to categorize the type of tangential traction either with IR and OCT (en face) for every single patient. Cohen's kappa statistic was used to evaluate inter-observer and inter-instrument agreement. RESULTS: Twenty eyes of 19 patients were included in the study. Inter-observer OCT test showed almost perfect agreement between examiners (κ = 0.86). Inter-observer IR test showed substantial agreement (κ = 0.7). Inter-instrument agreement was fair for both observers, respectively κ = 0.35 for observer 1 and κ = 0.22 for observer 2. Intra-observer agreement was almost perfect for OCT (κ = 0.93) and substantial for IR (κ = 0.78). CONCLUSION: Tangential traction associated with epiretinal membranes in lamellar macular holes can be successfully evaluated by OCT en face and IR reflectance. Inter-observer concordance is high for both instruments. However, high inter-instrument discordance is present. Therefore, the gold standard imaging technique for differentiating the different types of contraction in epiretinal membranes has still to be determined.

Long-term follow-up of fellow eye in patients with lamellar macular hole.

BACKGROUND: To evaluate macular changes in fellow eyes of patients diagnosed with lamellar macular hole (LMH) using spectral-domain optical coherence tomography (SD-OCT) and blue fundus autofluorescence (B-FAF). METHODS: Fellow eyes of patients diagnosed with a LMH were retrospectively evaluated on OCT. Best-corrected visual acuity (BCVA) and central foveal thickness (CFT) were recorded. Corresponding B-FAF images, vitreo-macular relations, and type of epiretinal membranes (ERMs) were also examined. RESULTS: Thirty-five patients were included. At baseline, six fellow eyes (17%) showed a normal foveal profile, 26 (74%) had a tractional ERM, and three cases (9%) revealed a bilateral LMH, one of them with a lamellar hole-associated epiretinal proliferation (LHEP). A posterior vitreous detachment (PVD) was present in 29 patients (83%), four (11%) had only a vitreo-papillary adhesion (VPA), and two (6%) had both vitreo-macular adhesion (VMA) and VPA. After a mean follow-up of 4.6 ± 1.9 years, one eye (3%) developed a vitreous detachment from the macula with persistent VPA, and one developed a PVD from a VPA with subsequent ERM formation. BCVA and mean CFT remained stable in 35 eyes (100%). Likewise, no B-FAF signal variations were detected. One patient developed a LMH during the 3rd year of follow-up. CONCLUSIONS: Our data suggest that the presence of a LMH in one eye does not increase significantly the risk of developing the same condition in the fellow eye after 4 years. Bilateral condition is uncommon, and an ERM is often detected in the fellow eye. LHEPs were not observed in fellow eyes with foveal integrity, and all LHEPs observed (in main and fellow eyes) were always associated with LMHs; this supports the hypothesis that LHEP is a consequence and not a causative factor for LMHs. The occurrence of a LMH in one fellow eye after 3 years follow-up may suggest that a higher incidence of bilateral disease could develop in a longer time span.