Serum Fusion Transcripts to Assess the Risk of Hepatocellular Carcinoma and the Impact of Cancer Treatment through Machine Learning.

Hepatocellular carcinoma (HCC) is one of the most fatal malignancies. Early diagnosis of HCC is crucial in reducing the risk for mortality. This study analyzed a panel of nine fusion transcripts in serum samples from 61 patients with HCC and 75 patients with non-HCC conditions, using TaqMan real-time quantitative RT-PCR. Seven of the nine fusions frequently detected in patients with HCC included: MAN2A1-FER (100%), SLC45A2-AMACR (62.3%), ZMPSTE24-ZMYM4 (62.3%), PTEN-NOLC1 (57.4%), CCNH-C5orf30 (55.7%), STAMBPL1-FAS (26.2%), and PCMTD1-SNTG1 (16.4%). Machine-learning models were constructed based on serum fusion-gene levels to predict HCC in the training cohort, using the leave-one-out cross-validation approach. One machine-learning model, called the four fusion genes logistic regression model (MAN2A1-FER≤40, CCNH-C5orf30≤38, SLC45A2-AMACR≤41, and PTEN-NOLC1≤40), produced accuracies of 91.5% and 83.3% in the training and testing cohorts, respectively. When serum α-fetal protein level was incorporated into the machine-learning model, a two fusion gene (MAN2A1-FER≤40, CCNH-C5orf30≤38) + α-fetal protein logistic regression model was found to generate an accuracy of 94.8% in the training cohort. The same model resulted in 95% accuracy in both the testing and combined cohorts. Cancer treatment was associated with reduced levels of most of the serum fusion transcripts. Serum fusion-gene machine-learning models may serve as important tools in screening for HCC and in monitoring the impact of HCC treatment.

Identification and characterization of CHD4-associated eRNA as a novel modulator of fetal hemoglobin levels in ß-thalassemia.

Fetal-to-adult hemoglobin switching is controlled by programmed silencing of γ-globin while the re-activation of fetal hemoglobin (HbF) is an effective strategy for ameliorating the clinical severity of ß-thalassemia and sickle cell disease. The identification of enhancer RNAs (eRNAs) related to the fetal (α2γ2) to adult hemoglobin (α2ß2) switching remains incomplete. In this study, the transcriptomes of GYPA+ cells from six ß-thalassemia patients with extreme HbF levels were sequenced to identify differences in patterns of noncoding RNA expression. It is interesting that an enhancer upstream of CHD4, an HbF-related core subunit of the NuRD complex, was differentially transcribed. We found a significantly positive correlation of eRNA-CHD4 enhancer-gene interaction using the public database of FANTOM5. Specifically, the eRNA-CHD4 expression was found to be significantly higher in both CD34+ HSPCs and HUDEP-2 than those in K562 cells which commonly expressed high level of HbF, suggesting a correlation between eRNA and HbF expression. Furthermore, prediction of transcription binding sites of cis-eQTLs and the CHD4 genomic region revealed a putative interaction site between rs73264846 and ZNF410, a known transcription factor regulating HbF expression. Moreover, in-vitro validation showed that the inhibition of eRNA could reduce the expression of HBG expression in HUDEP-2 cells. Taken together, the findings of this study demonstrate that a distal enhancer contributes to stage-specific silencing of γ-globin genes through direct modulation of CHD4 expression and provide insights into the epigenetic mechanisms of NuRD-mediated hemoglobin switching.

Fusion Gene Detection in Prostate Cancer Samples Enhances the Prediction of Prostate Cancer Clinical Outcomes from Radical Prostatectomy through Machine Learning in a Multi-Institutional Analysis.

Prostate cancer remains one of the most fatal malignancies in men in the United States. Predicting the course of prostate cancer is challenging given that only a fraction of prostate cancer patients experience cancer recurrence after radical prostatectomy or radiation therapy. This study examined the expressions of 14 fusion genes in 607 prostate cancer samples from the University of Pittsburgh, Stanford University, and the University of Wisconsin-Madison. The profiling of 14 fusion genes was integrated with Gleason score of the primary prostate cancer and serum prostate-specific antigen level to develop machine-learning models to predict the recurrence of prostate cancer after radical prostatectomy. Machine-learning algorithms were developed by analysis of the data from the University of Pittsburgh cohort as a training set using the leave-one-out cross-validation method. These algorithms were then applied to the data set from the combined Stanford/Wisconsin cohort (testing set). The results showed that the addition of fusion gene profiling consistently improved the prediction accuracy rate of prostate cancer recurrence by Gleason score, serum prostate-specific antigen level, or a combination of both. These improvements occurred in both the training and testing cohorts and were corroborated by multiple models.

PREDICTIVE FACTORS ASSOCIATED WITH THE VISUAL PROGNOSIS AFTER SURGERY FOR IDIOPATHIC VITREOMACULAR TRACTION.

PURPOSE: To investigate the predictive factors for postsurgical visual prognosis in patients with vitreomacular traction (VMT). METHODS: This retrospective study enrolled 31 eyes from 29 patients who underwent vitrectomy for idiopathic VMT with a follow-up period of ≥3 months. The VMT was divided into three grades based on optical coherence tomography images: Grade 1 denoted partial vitreomacular separation with foveal attachment; Grade 2 exhibited intraretinal cysts or cleft with grade 1 findings; and Grade 3 was Grade 2 plus the subretinal fluid. RESULTS: Three eyes developed a full-thickness macular hole after surgery, all of which were Grade 3 patients. In the rest 28 eyes, the mean postoperative follow-up period was 23.3 ± 25.8 months. The postoperative central foveal thickness ( P = 0.001) and final best-corrected visual acuity (BCVA; P < 0.001) were both significantly improved from baseline. Fifteen eyes (53.8%) gained ≥ two Snellen lines. Multilinear regression analysis showed that the worse the baseline BCVA ( P = 0.004), or the more advanced the VMT grade ( P = 0.049), the worse the final BCVA. Baseline BCVA was negatively associated with the postoperative visual improvement ( P < 0.001). Those Grade 3 patients with baseline Snellen BCVA of ≥20/40 were more likely to achieve a final Snellen BCVA of ≥20/25 ( P = 0.035). CONCLUSION: The VMT grade is an important predictive factor for the postsurgical visual prognosis. Surgical intervention should be performed as early as possible for Grade 3 patients to prevent further disease progression and maximize the postsurgical visual benefit.

Closure Grading and Visual Outcome in Patients with Large Idiopathic Macular Holes: A Spectral-Domain Optical Coherence Tomography Observation.

INTRODUCTION: So far, there has been no closure grade system synthesizing morphological and microstructural features for large idiopathic macular holes (IMHs) treated by vitrectomy and internal limiting membrane (ILM) peeling. This study aimed to propose a concise one and explore its relevance with visual acuity and the related preoperative factors. METHODS: Consecutive patients with large IMHs (minimum diameter >400 µm), undergoing vitrectomy and ILM peeling, obtaining primary closure and regularly followed-up were enrolled. Preoperative clinical charts and spectral-domain optical coherence tomography (SD-OCT) parameters were reviewed. SD-OCT images and best corrected visual acuity (BCVA) were assessed at 1, 4, and 10 months postoperatively. SD-OCT features at last visit were categorized by BCVA significance, and preoperative risk factors were analyzed. RESULTS: Sixty-eight eyes from 64 patients were enrolled. The 10-month postoperative SD-OCT images were categorized into closure grade 1, 2, and 3 with successively decreased BCVA (p < 0.001). During early follow-up, part of grades 2 and 3 could evolve into the upper grade, respectively, but grade 3 could never evolve into grade 1 and exhibited the least satisfactory long-term BCVA. Binary logistic regression showed that large minimum linear diameter (MLD) was a risk factor for grade 3 occurrence (p < 0.001), with a cutoff value of 625.5 µm from the receiver operating characteristic curve for MLD predicting grade 3 occurrence (p = 0.001). CONCLUSION: Long-term closure status of large IMHs could be categorized into three grades with BCVA significance. Large horizontal MLD is a risk factor for occurrence of grade 3 closure with unsatisfactory visual recovery.

Foveal Microstructure and Visual Outcomes after Pars Plana Vitrectomy in Patients with Different Types of Epiretinal Membrane Foveoschisis.

INTRODUCTION: The aim of this study was to evaluate the clinical characteristics and surgical outcomes of the epiretinal membrane foveoschisis (ERM-FS) with different morphological types. METHODS: This retrospective observational study reviewed 44 consecutive ERM-FS patients who underwent ERM surgery. According to the optical coherence tomography images, ERM-FS was classified into three groups: group A, FS crossed the fovea with the foveola elevated; group B, FS located at the foveal edges with a near-normal central foveal point thickness; and group C, FS with undermined foveal edges with a near-normal central foveal point thickness. RESULTS: There were 10 eyes in group A, 20 eyes in group B, and 14 eyes in group C. Preoperatively, eyes in group A had the best best-corrected visual acuity (BCVA), the thickest central foveal point thickness, and the highest ellipsoid zone (EZ) intact rate among the three groups. After surgery, a resolution of foveoschisis was observed in 40.0%, 45.0%, and 50.0% of the eyes in group A, group B, and group C (p = 0.928), respectively. BCVA was significantly improved postoperatively. Although there was no significant difference in BCVA among the three groups at 1 month postoperatively, BCVA of group A was the best at 4 and 10 months. Correlation analysis indicated that the type of ERM-FS, baseline BCVA, central foveal point thickness, and postoperative EZ continuity (all p < 0.05) were important factors for the final BCVA. CONCLUSIONS: The damage to the retinal structure and visual function was milder in group A ERM-FS. Our study emphasized the necessity of OCT-based subtyping in patients with ERM-FS.

Changes in foveal photoreceptor integrity after idiopathic epiretinal membrane surgery and its relationship with visual outcomes.

PURPOSE: To investigate the changes in the external limiting membrane (ELM), ellipsoid zone (EZ), and interdigitation zone (IZ) integrity and their relationship with visual outcomes after idiopathic epiretinal membranes peeling. METHODS: Clinical records of 150 eyes from 144 consecutive patients who underwent vitrectomy were reviewed. The status of IZ, EZ, and ELM was assessed by spectral-domain optical coherence tomography at baseline and 1, 4, 10, and 24 months postoperatively. RESULTS: Sixty-one eyes presented with photoreceptor layer disruption preoperatively, and IZ disruption (40.7%) was the primary type. The best-corrected visual acuity (BCVA) in the photoreceptor disruption group was significantly lower than that in the intact group at baseline and the final follow-up. Of them, ELM + EZ + IZ disruption showed the worst BCVA (P = 0.001). After surgery, 62 eyes were observed with disruption aggravated. EZ + IZ disruption (51.0%) was the most frequent type at 1 month postoperatively. The eyes with longer symptom duration, better BCVA, earlier stage, thinner CFT at baseline, and combined cataract surgery more tended to be observed with photoreceptor damage progressed after surgery (P < 0.05). There was no significant difference in the final BCVA between the eyes with and without damage progressed (P = 0.332). Finally, 28.1% of the eyes recovered photoreceptor continuity. The eyes with foveal photoreceptor integrity restored had better BCVA than those remaining discontinuous (P < 0.001). CONCLUSION: ERM-induced photoreceptor disruption mainly manifests as IZ disruption and has a negative effect on BCVA, whereas surgery mainly causes EZ and IZ disruption, which does not have a significant impact on the final BCVA.

Clinical features of idiopathic epiretinal membrane in children and the factors influencing postoperative visual acuity.

PURPOSE: To describe the characteristics and surgical outcomes of idiopathic epiretinal membrane (iERM) in children and to determine the factors associated with postoperative visual acuity (VA). METHODS: We retrospectively reviewed the medical records of 17 patients with iERM (age, < 18 years) who had undergone ERM surgery from 2009 to 2021. Spectral-domain optical coherence tomography features were documented. The eyes with iERMs involving the fovea were assigned to the localized and diffused groups depending on the morphological description of the membrane. Multiple linear regression analysis was used to explore the factors associated with the final VA. RESULTS: The mean age was 9.2 ± 3.8 years. The mean follow-up period was 38.9 ± 45.4 months. After surgery, the central foveal thickness and the best-corrected VA (BCVA) improved significantly (all, P < 0.05). Fourteen eyes with iERMs showed involvement of the foveal area (localized group, six eyes; diffused group, eight eyes). There were no significant differences in the preoperative BCVA between the two groups (P = 0.064). However, the final BCVA was better in the diffused group than in the localized group (P = 0.043). Multiple regression analysis indicated that the localized membrane (P = 0.042) and lower preoperative BCVA (P = 0.043) were factors associated with a worse final VA in pediatric iERMs. CONCLUSIONS: Surgical removal of ERM showed a high anatomical and functional success rate in children. In pediatric patients with iERMs involving the fovea, a good VA was more common when the membrane was diffused than when it was localized.

Observation of macular hole associated with retinoschisis in patients with high myopia.

PURPOSE: To observe the characteristics of highly myopic macular holes (HMMHs) with macular retinoschisis (MRS) by optical coherence tomography (OCT) and explore the possible relationship between HMMHs and different types of MRS. METHODS: We consecutively reviewed the clinical data and OCT images of the patients with HMMHs from June 2015 to February 2021. Then we picked eyes with MRS from these HMMHs for analysis. The minimum linear diameter (MLD), basal diameter (BD), and height (H) of HMMHs were measured. HMMHs were grouped according to the extent or layer involvement of the concomitant MRS and the characteristics were compared among groups. The impact of MRS on the MLD of macular hole was analyzed with multivariable linear regression. RESULTS: We included 127 patients with MRS from 168 HMMHs (75.5%) for analysis. According to the different classification systems, the most frequent type of MRS in HMMHs was S3 (foveal but not entire macular area MRS) (62.2%) and both inner- and outer- (I/O-MRS) involved types. In our study, HMMHs with more extensive MRS had larger MLD, larger BD, larger H, and poorer best-corrected visual acuity (BCVA). Meanwhile, HMMHs with outer layer-involved MRS (outer MRS and I/O-MRS) had larger BD than HMMH with only inner layer-involved MRS. (All P < 0.05) Multivariable linear regression further illustrated only the extent of MRS was significantly associated with the MLD of HMMH, while there was no significant correlation between the involved retinal layers and the MLD of HMMH. CONCLUSION: HMMH with MRS presented as a predominant type in HMMHs. The MRS was always with a relatively large extent and involved both inner and outer layers. MLD of HMMH was mainly affected by the extent of MRS.

CLINICAL CHARACTERISTICS AND SURGICAL PROGNOSIS OF IDIOPATHIC MACULAR HOLES WITH EPIRETINAL PROLIFERATION.

PURPOSE: To investigate the clinical features and surgical outcomes of idiopathic macular holes with epiretinal proliferation (EP). METHODS: This retrospective study included 282 eyes of 269 consecutive patients who underwent vitrectomy for idiopathic macular holes. Clinical demographic data, baseline and postoperative retinal microstructure features on optical coherence tomography images, best-corrected visual acuity, and postoperative closure rate were compared between eyes with and without EP. RESULTS: EP was identified in 38 of 282 eyes (13.5%). Eyes with EP had a significantly longer symptom duration ( P = 0.019), higher frequency of pseudophakic conditions ( P = 0.034), presence of epiretinal membrane ( P < 0.001), and a larger base diameter ( P = 0.014) than those without EP. In addition, compared with eyes without EP, those with EP had a higher percentage of U-type closure ( P = 0.047) and a thicker central fovea ( P = 0.012) at 1 month postoperatively and a significantly lower frequency of ellipsoid zone disruption ( P = 0.033) and outer foveolar lucency ( P = 0.021) and a thicker central fovea ( P = 0.004) at 10 months postoperatively. CONCLUSION: The presence of EP represents a more chronic pathogenic process but has no negative effect on postoperative outcomes and can even facilitate anatomical recovery after surgery.

COMPARISON OF AIR VERSUS PERFLUOROPROPANE INTRAOCULAR TAMPONADE COMBINED WITH VITRECTOMY FOR THE TREATMENT OF MACULAR HOLE IN HIGH MYOPIA.

PURPOSE: To compare the efficacy of air and perfluoropropane (C3F8) with pars plana vitrectomy (PPV) in highly myopic macular holes (HMMHs) and explore the factors related to surgical prognosis. METHODS: A retrospective comparison of a consecutive series of HMMHs undergone vitrectomy and internal limiting membrane peeling. According to tamponade type, they were divided into air group and C3F8 group, which were further divided into subgroups based on hole diameter or axial length (AXL). Anatomical and functional outcomes were compared between tamponades. Related factors of initial closure rate and postoperative best-corrected visual acuity (BCVA) were analyzed by logistic regression. RESULTS: The baseline characteristics in air group (n = 63) and C3F8 group (n = 37) were similar except the age of air was older ( P = 0.019). The mean follow-up period was 17.16 ± 17.97 months. After surgery, the initial closure rate of air group was 85.7% and that of C3F8 group was 83.7% ( P = 0.780). And the initial closure rate showed no difference between tamponades in the same subgroup classified by hole diameter or AXL (all P > 0.05). Postoperative BCVA improved significantly in both groups ( P < 0.001), but no difference between them ( P = 0.793). Logistic regression showed that age, minimum linear diameter, and AXL were risk factors of initial closure rate, and preoperative BCVA was the only factor associated with postoperative BCVA (all P < 0.05). CONCLUSION: With a long-term follow-up of HMMH, we found air had a similar tamponade effect anatomically and functionally compared with C3F8. Air may also be a good choice for patients with HMMH.

DIFFERENCES IN ANATOMICAL AND VISUAL OUTCOMES AMONG THREE INTERNAL LIMITING MEMBRANE TECHNIQUES TREATING EXTRA-LARGE IDIOPATHIC MACULAR HOLES.

PURPOSE: To compare the anatomical and visual outcomes of extra-large idiopathic macular holes treated with internal limiting membrane peeling and two inverted internal limiting membrane flap techniques, namely insertion and cover technique. METHODS: Patients with idiopathic macular holes (minimum linear diameter ≥ 650 µm) were divided into peeling group, insertion group, and cover group. The initial closure rate, final length of external limiting membrane and ellipsoid zone recovery, and best-corrected visual acuity were evaluated. RESULTS: A total of 124 eyes were included, and the average follow-up was 7.2 months. All the baseline characteristics were comparable among the three groups. Initial closure rate of the peeling group, the insertion group, and the cover group was 65.0% (26/40), 97.6% (41/42), and 90.5% (38/42), respectively (P < 0.001). In closed idiopathic macular holes, the peeling group and the cover group exhibited significantly longer length of external limiting membrane recovery than the insertion group (P < 0.001), and the peeling group exhibited significantly longer length of ellipsoid zone recovery than the other two groups (P = 0.021). The peeling group and the cover group exhibited significantly better best-corrected visual acuity improvement than the insertion group (P = 0.009). CONCLUSION: For extra-large idiopathic macular holes, cover technique surpasses internal limiting membrane peeling technique in closure rate and outperforms insertion technique in anatomical and functional recovery, whereas insertion technique may adversely affect the recovery of foveal microstructure and best-corrected visual acuity.

Stage or size? The identity of anatomical and visual outcomes in stage 3 and stage 4 idiopathic macular holes after vitrectomy.

BACKGROUND: Several previous reports suggested that stage 4 idiopathic macular holes (IMHs) may exhibit lower rate of anatomical success and poorer functional results comparing with stage 3 IMHs, while some others showed no differences. Actually, few studies focused on comparison of prognosis between stage 3 and stage 4 IMHs. Our previous study found that IMHs of these two stages demonstrate similar preoperative characteristics, and this study aims to compare anatomical and visual outcomes of IMHs between stage 3 and stage 4, and tries to figure out the outcome-associated factors. METHODS: This retrospective consecutive case series reviewed 317 eyes with IMHs of stage 3 and stage 4 from 296 patients who underwent vitrectomy with internal limiting membrane peeling. Preoperative characteristics like age, gender, and hole size, and intraoperative interventions such as combined cataract surgery were evaluated. Outcome measures included the primary closure rate (type 1), best-corrected visual acuity (BCVA), foveal retinal thickness (FRT) and prevalence of outer retinal defect (ORD) at the last visit. The pre-, intra-, and post-operative information were respectively compared between stage 3 and stage 4. RESULTS: The preoperative characteristics and intraoperative interventions exhibited no significant differences between stages. With comparable follow-up durations (6.6 vs. 6.7 months, P = 0.79), IMHs of the two stages exhibited similar primary closure rate (91.2% vs. 91.8%, P = 0.85), BCVA (0.51 ± 0.12 vs. 0.53 ± 0.11, P = 0.78), FRT (134.8 ± 55.5 µm vs. 138.8 ± 60.7 µm, P = 0.58), and prevalence of ORD (55.1% vs. 52.6%, P = 0.39). IMHs, either < 650 µm or larger, exhibited no significant difference in outcomes between the two stages. However, smaller IMHs (< 650 µm) demonstrated higher rate of primary closure (97.6% vs. 80.8%, P < 0.001), better postoperative BCVA (0.58 ± 0.26 vs. 0.37 ± 0.24, P < 0.001), and thicker postoperative FRT (150.2 ± 54.0 vs. 104.3 ± 52.0, P < 0.001) comparing with larger ones regardless of stage. CONCLUSION: IMHs of stage 3 and stage 4 exhibited considerable identity of anatomical and visual outcomes. In large IMHs, the hole size, instead of stage, may be more important for prediction of surgical outcomes and choice of surgical techniques.

A novel missense variant expands the phenotype and genotype of PAX6-associated foveal hypoplasia accompanied by various manifestations of anterior segment dysgenesis.

BACKGROUND: According to previous reports, PAX6-associated foveal hypoplasia (FH) could usually be accompanied by various anterior segment anomalies including variable iris changes. This study aims to exhibit unusual phenotypes of a novel missense variant of PAX6 from a Chinese pedigree. METHODS: Ophthalmic examinations including slit-lamp biomicroscopy, gonioscopy, ophthalmic ultrasound, ultrasonic biomicroscopy, optical coherence tomography, wide-field fundus imaging, and visual field test were performed to evaluate the clinical manifestations. Whole-exome sequencing (WES) and bioinformatics analysis were conducted in eight members from this pedigree to identify the causative mutation. RESULTS: WES revealed a novel heterozygous substitution of PAX6 (NM_000280.5:c.157G > A, p.(Val53Met) (chr11:31823309 C > T, hg19)), which cosegregated with the phenotype of this pedigree. All the three patients (a pair of fraternal twins and their mother) exhibited bilateral FH and anterior segment dysgenesis (ASD) including microcornea, sclerocornea, obvious symmetrical corectopia, iris stromal dysplasia, goniodysgenesis, and abnormal distribution of fundus blood vessels. The girl of the fraternal twins also demonstrated bilateral temporal deviation of lenses and abnormal tissue membrane connecting anterior chamber angle and lens anterior capsule in the right eye. The mother additionally showed apparent cataract bilaterally and cupping of the optic disc in her left eye. CONCLUSION: A novel missense variant in PAX6 gene was detected in a Chinese pedigree demonstrating bilateral FH and ASD. It is really distinctive that the ASD involves almost all parts of the anterior segment, and bilateral symmetrical corectopia is the most perceptible sign. This study expands the phenotypic and genotypic spectrum of PAX6-associated ocular diseases, and facilitates the understanding of the crucial role that PAX6 plays in the development of the eye. Meanwhile, PAX6 could be considered as a candidate pathogenic gene of bilateral symmetrical corectopia.

Microstructural and microperimetric comparison of internal limiting membrane peeling and insertion in large idiopathic macular hole.

BACKGROUND: The internal limiting membrane (ILM) insertion technique was widely used to treat large macular hole (MH) for the high closure rate. However, the prognosis of closed MH after ILM insertion compared to ILM peeling remains controversial. This study aimed to compare foveal microstructure and microperimeter in large idiopathic MH surgically closed by ILM peeling and ILM insertion. METHODS: This retrospective, non-randomized, comparative study included patients with idiopathic MH (minimum diameter ≥ 650 µm) who underwent primary pars plana vitrectomy (PPV) with ILM peeling or ILM insertion. The initial closure rate was recorded. Patients with initially closed MHs were divided into two groups according to the surgery methods. The best-corrected visual acuity (BCVA), optical coherence tomography (OCT) and microperimeter-3 (MP-3) outcomes of two groups were compared at baseline, 1 and 4 months postoperatively. RESULTS: For idiopathic MH (minimum diameter ≥ 650 µm), ILM insertion had a significantly higher initial closure rate than ILM peeling (71.19% vs. 97.62%, P = 0.001). Among 39 patients with initially closed MHs who were on regular follow-up, twenty-one were assigned to the ILM peeling group and 18 to the ILM insertion group. Postoperative BCVA improved significantly in both groups. The final BCVA (logMAR) (0.40 vs. 0.88, P < 0.001), macular hole sensitivity (19.66 dB vs. 14.14 dB, P < 0.001), peripheral sensitivity of macular hole (24.63 dB vs. 21.95 dB, P = 0.005), and fixation stability (FS) within 2 degrees (82.42% vs. 70.57%, P = 0.031) were significantly better and external limiting membrane (ELM) defect (330.14 µm vs. 788.28 µm, P < 0.001) and ellipsoid zone (EZ) defect (746.95 µm vs. 1105.11 µm, P = 0.010) were significantly smaller in the ILM peeling group than in the ILM insertion group. CONCLUSION: For initially closed MHs (minimum diameter ≥ 650 µm), both ILM peeling and ILM insertion significantly improved the microstructure and microperimeter in the fovea. However, ILM insertion was less efficient at microstructural and functional recovery after surgery.

Morphological Characteristics of Foveal Pit Base and Its Impact on Visual Acuity in Macular Pseudoholes.

INTRODUCTION: To investigate the characteristics of macular pseudoholes (MPHs) with different foveal profiles and their impact on preoperative and postoperative visual acuity (VA). METHODS: A retrospective review of 47 eyes from 46 consecutive patients with MPH who had undergone vitrectomy was conducted. The MPHs were classified into u-shape and v-shape according to the morphological description of the foveola base. The best-corrected visual acuity (BCVA), central foveal point thickness, parafoveal thickness, parafoveal inner and outer retinal thickness, stretched lamellar cleavage, microcystic macular edema (MME), disorganization of retinal inner layers (DRIL), and the integrity of outer retinal layers were recorded. RESULTS: The eyes in the v-shaped group (n = 31) had lower BCVA, thicker retinal thickness, more intraretinal cleavage, MME, and DRIL than the u-shaped (n = 16) group (all p < 0.05). Multiple regression analysis revealed that the morphology of the foveola base was significantly related to the preoperative BCVA (p = 0.025). The VA was significantly improved in both groups, and the improvement was greater in the v-shaped group (p = 0.024). No significant difference was found in the postoperative BCVA between the two groups (all p > 0.05). CONCLUSION: The v-shape, reflecting the stretch in the foveola, had a significant impact on preoperative BCVA. However, the VA was improved after surgery whatever their initial foveal profile.

The Evolution and Visual Prognosis of Glial Proliferation with Different Grades after Macular Hole Surgery: An Optical Coherence Tomography-Based Study.

INTRODUCTION: The glial proliferation after macular hole (MH) surgery was divided into two types previously: those replacing the entire intraretinal layer and those involving only the inner foveal layers. The evolution and prognosis of the former type were elaborated on in previous studies, but the latter one has received limited attention. Therefore, this study aims to investigate the evolution of glial proliferation with varying grades after MH surgery and its effects on foveal microstructure and best-corrected visual acuity (BCVA). METHODS: In this retrospective research, we reviewed 202 eyes from 196 consecutive patients who underwent a successful idiopathic MHs repair. Based on optical coherence tomography images, glial proliferation was classified into three types: A-type, which replaced the entire intraretinal layer; B-type, located at the level of and above the external limiting membrane (ELM); and C-type, situated above the ELM. RESULTS: Of the 67 eyes that attended the 1-, 4-, and 10-month follow-up, A-type, B-type, C-type, and no glial proliferation were identified in 27 (40.3%), 17 (25.4%), 20 (29.8%), and 3 eyes (4.5%), respectively, at 1 month. Within 10 months, the prevalence of A-type glial proliferation significantly decreased (p < 0.001), but the changes in B-type (p = 0.261), C-type (p = 0.151), and no glial proliferation (p = 0.492) were not significant. In 32 of the 67 eyes, the grade of glial proliferation gradually improved, with A-type transforming into B- or C-type in 19 of 27 eyes (70.4%), B-type into C-type or no glial proliferation in 11 out of 17 eyes (64.7%), and C-type gradually disappearing in 2 out of 20 eyes (10.0%). Among the eyes that attended at least one follow-up (1 M, 202 eyes; 4 M, 161 eyes; 10 M, 97 eyes), those with A-type glial proliferation showed the most defective outer retinal layers, worst BCVA, and thinnest central fovea compared with the other two types at all follow-up time points (p < 0.001). Eyes with C-type glial proliferation exhibited significantly better photoreceptor layer status and BCVA compared with those with B-type glial proliferation. A-type glial proliferation at 1 month, which showed significant association with BCVA at 10 months, could be accurately predicted by the minimum linear diameter with a cut-off >547.5 µm (p < 0.001). CONCLUSION: Within 10 months, A-type glial proliferation substantially resolves but the prevalence of B- and C-type remains unchanged. B-type glial proliferation hinders the restoration of photoreceptors and impairs visual recovery despite being located within the inner retina.

Photoreceptor Outer Segment Loss at the Macular Hole Border: Clinical Characteristics and Surgical Prognosis.

INTRODUCTION: During macular hole (MH) formation, the vitreofoveal traction may lead to foveal neural tissue avulsion and consequent photoreceptor loss. However, the clinical significance of the photoreceptor outer segment disruption at the MH border remains unclear. This study aims to investigate the clinical features and surgical outcomes of MHs with photoreceptor outer segment disruption at the MH border. METHODS: This study retrospectively reviewed 86 eyes from 85 patients who underwent vitrectomy combined with internal limiting membrane peeling for idiopathic MHs. Baseline and postoperative best-corrected visual acuity (BCVA) and foveal microstructure on optical coherence tomography images were compared between eyes with smooth and bumpy morphology, the latter of which was defined as those with an uneven and irregular surface with evident lumps and indentations at the MH border. RESULTS: The bumpy morphology was identified in 59 of 86 eyes (68.9%). At baseline, eyes with a bumpy MH morphology had a significantly larger minimum linear diameter (p = 0.043), a longer external limiting membrane defect (p = 0.013), and a worse baseline BCVA (p = 0.017) than those with a smooth morphology. Postoperatively, in a multivariate regression model adjusting preoperative confounding effects, eyes with bumpy borders were associated with a longer ellipsoid zone defect (p = 0.006) and a thinner central fovea (p = 0.002) at 1 month, and a thinner central fovea (p = 0.005) and a worse BCVA (p = 0.015) at 10 months. CONCLUSION: A severe photoreceptor outer segment loss is common at the MH border, which represents a chronic pathogenic process and may be an independent predictor for an incomplete photoreceptor recovery and worse long-term visual outcomes after surgery.

Simultaneous separation and determination of six furanocoumarins in Radix Angelicae dahuricae by CZE with dual CDs system.

A novel, simple and efficient capillary electrophoresis method was developed to simultaneous determination of six furanocoumarins (psoralen, isopsoralen, imperatorin, isoimperatorin, phellopterin, and cnidilin). The separation buffer consisted of 30 mM boric acid, 12 mM sulfobutylether-ß-cyclodextrin and 1.5 mM 2-hydroxypropyl-ß-cyclodextrin (pH 7.8); the voltage was 20 kV, the temperature was 25 °C and the detection wavelength was at 246 nm with a diode array detector (DAD). Under the above conditions, the analytes could be separated with high resolution in less than 7 min. This method was used to simultaneously determine the content of psoralen, imperatorin, isoimperatorin and phellopterin in Angelica Dahurica Radix. And good linearities were obtained with correlation coefficients from 0.9992 to 0.9999. The limits of detection (LOD, S/N = 3) and the limits of quantitation (LOQ, S/N = 10) ranged from 0.6 to 3.0 µg/mL and from 2.1 to 9.9 µg/mL, respectively. The recoveries ranged between 98.8% and 101.8%. The results indicated the method can achieve baseline separation and quantitative analysis of furanocoumarins in Chinese herbal medicines and formulations.

Simultaneous separation and determination of five chlorogenic acid isomers in Honeysuckle by capillary electrophoresis using self-synthesized ionic liquid [N-methylimidazole-ß-cyclodextrin] [bromide] as separation selector.

A simple, comprehensive, and efficient capillary electrophoresis method using a self-synthesized ionic liquid [N-methylimidazole-ß-cyclodextrin] [bromide] as a separation selector was developed for the simultaneous separation and determination of five chlorogenic acid isomers (chlorogenic acid, cryptochlorogenic acid, neochlorogenic acid, isochlorogenic acid A, isochlorogenic acid B). After optimization of separation conditions, the electrolyte solution was 50 mM ammonium acetate buffer containing 0.7% (w/w) ionic liquid [N-methylimidazole-ß-cyclodextrin] [bromide] (pH 4.8), 15 kV of the electric field was applied at 25°C, and the detection wavelength was at 237 nm. Under the optimal separation conditions, good linearities were obtained with linear correlation coefficients of the five analytes of 0.9994-0.9998, and the limits of detection and the limits of quantification were 0.6-2.8 and 2.2-9.5 µg/ml. Excellent accuracy and precision were obtained for the five analytes. The intraday and interday precision of standards ranged from 0.5 to 1.3% and from 1.2 to 1.9%. The intraday and interday precision of samples ranged from 1.0 to 1.9% and from 1.2 to 2.6%. The sample recovery rates were between 98.0 and 101.8%. This method was successfully applied for the analysis of five components in Honeysuckle Chinese medicinal preparations. The mechanisms involved in the separation of five analytes by [N-methylimidazole-ß-cyclodextrin] [bromide] were discussed.