Brolucizumab in recalcitrant neovascular age-related macular degeneration-real-world data in Chinese population.

This retrospective study aimed to determine the short-term efficacy and safety of brolucizumab treatment for recalcitrant neovascular age-related macular degeneration (nAMD) in a real-world setting in Taiwan. Recalcitrant nAMD patients who were treated with brolucizumab from November 2021 to August 2022 at Taipei Veterans General Hospital were included. Patients were followed for 3 months after switching to brolucizumab. The primary outcomes were changes in mean best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline to the third month. The secondary outcomes included the incidence of intraocular inflammation (IOI), proportion of patients with subretinal and intraretinal fluid (SRF and IRF), and change in pigment epithelial detachment (PED) height from baseline to the third month. The significance level was considered as p < .05 in all tests. A total of 38 patients (40 eyes) with a mean (±SD) age of 76.3 (±10.84) years were included. The baseline BCVA was 0.92±0.64 logMAR, and the CRT and PED height were 329.0±171.18 and 189.8±114.94 um, respectively. The patients had a significant reduction in CRT and resolution of IRF and SRF from baseline to the third month. There were numerical improvements in mean BCVA and PED height, but they were not significant. The percentages of achieving at least 0.1, 0.2, and 0.3 logMAR (equivalent to 5, 10, 15 ETDRS letters) visual gain were 50%, 37.5%, and 30%, respectively, during the first 3 months of follow-up. No IOI occurred in these patients. This study demonstrated that brolucizumab had good short-term structural and functional efficacy in recalcitrant nAMD patients.

HLA-Homozygous iPSC-Derived Mesenchymal Stem Cells Rescue Rotenone-Induced Experimental Leber's Hereditary Optic Neuropathy-like Models In Vitro and In Vivo.

BACKGROUND: Mesenchymal stem cells (MSCs) hold promise for cell-based therapy, yet the sourcing, quality, and invasive methods of MSCs impede their mass production and quality control. Induced pluripotent stem cell (iPSC)-derived MSCs (iMSCs) can be infinitely expanded, providing advantages over conventional MSCs in terms of meeting unmet clinical demands. METHODS: The potential of MSC therapy for Leber's hereditary optic neuropathy (LHON) remains uncertain. In this study, we used HLA-homozygous induced pluripotent stem cells to generate iMSCs using a defined protocol, and we examined their therapeutic potential in rotenone-induced LHON-like models in vitro and in vivo. RESULTS: The iMSCs did not cause any tumorigenic incidence or inflammation-related lesions after intravitreal transplantation, and they remained viable for at least nine days in the mouse recipient's eyes. In addition, iMSCs exhibited significant efficacy in safeguarding retinal ganglion cells (RGCs) from rotenone-induced cytotoxicity in vitro, and they ameliorated CGL+IPL layer thinning and RGC loss in vivo. Optical coherence tomography (OCT) and an electroretinogram demonstrated that iMSCs not only prevented RGC loss and impairments to the retinal architecture, but they also improved retinal electrophysiology performance. CONCLUSION: The generation of iMSCs via the HLA homozygosity of iPSCs offers a compelling avenue for overcoming the current limitations of MSC-based therapies. The results underscore the potential of iMSCs when addressing retinal disorders, and they highlight their clinical significance, offering renewed hope for individuals affected by LHON and other inherited retinal conditions.

Same-Day Bilateral Intravitreal Dexamethasone Implants for the Treatment of Diabetic Macular Edema.

INTRODUCTION: The aim of this study was to evaluate the outcomes and complications associated with the use of same-day bilateral intravitreal dexamethasone (DEX) implants for the treatment of diabetic macular edema (DME). METHODS: This retrospective analysis of an open-label, multicenter, consecutive case series included 130 eyes of 65 patients with bilateral DME who were treated with intravitreal DEX implants. The patients were divided into two groups: a control group (comprising 40 eyes treated with an alternating unilateral regimen) and a study group (comprising 90 eyes treated with concomitant bilateral DEX implants). All patients were followed up monthly after implantation. The changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline to sixth month after implantation, and ocular adverse effects such as intraocular pressure, cataract, and tolerability of bilateral implantation were reviewed. The primary endpoint was to assess the safety of the same-day bilateral treatment protocol. The secondary endpoints focused on evaluating the functional and anatomical changes associated with bilateral simultaneous or alternating implantations. RESULTS: At 6 months after implantation, mean BCVA increased and CRT decreased in both groups. Moreover, no serious ocular adverse effects were observed. In addition, no differences were observed between the two groups in the number of patients who required extra follow-up visits or the number of extra visits made in addition to the treatment schedule. CONCLUSIONS: Same-day bilateral intravitreal DEX implants are associated with a low complication rate and are well tolerated by patients. This safe practice may optimize efficiency and reduce the burden on both the health-care system and patients, when used to treat bilateral DME.

Assessment of histological and immunohistochemical features of retinal tissues using a novel tissue submission procedure.

We introduce a novel tissue submission procedure without additional equipment or storage facilities for assessing the histological and immunohistochemical features of retinal tissues. In total, 150 specimens were collected from patients who underwent vitrectomy or macular surgery from January to December 2020. Ninety-eight specimens were submitted using the new procedure, and 58 specimens were submitted as flat-mount slides to compare specimen adequacy. The tissues submitted using the new procedure were subjected to paraffin-embedding and sectioning for hematoxylin & eosin staining. Additional immunohistochemical analysis was performed to assess the cellular composition in retinal tissues with diverse etiologies. The new submission procedure had an adequacy ratio of 75.51%, which was comparable to that of the flat-mount method (p = 0.1397). The new method could produce high-quality images of histological features of tissues and facilitated immunohistochemical analysis to demonstrate cell origins. More glial cells (p = 0.000) and myofibroblasts (p = 0.012) were detected in the epiretinal membranes (ERMs) than in the internal limiting membranes (ILMs). Subgroup analysis revealed that secondary ERMs contained more macrophage-like cells (p = 0.001) and retinal pigment epithelial cells (p = 0.000) than did idiopathic ERMs. Our novel tissue submission procedure can be applied to routine clinical practice. Our study provides additional histological and immunohistochemical evidence of cellular components in retinal tissues based on a large number of human tissue samples. Moreover, tissues submitted using the new method can be permanently preserved, enabling future investigation for potential prognostic or therapeutic targets.

A Simple New Technique to Peel Epiretinal Membrane Without Removing Silicone Oil.

PURPOSE: To introduce a new surgical technique that can keep constant intraocular pressure of the eyeball during peeling epiretinal membrane under silicone oil status. METHODS: A viscoelastic agent was injected into the air pump of the constellation system via the metal tip. This procedure offers a buffer zone to keep constant pressure within the eyeball without disturbing the surgical field by an air bubble. RESULTS: Three cases were performed efficiently (15 ± 5 minutes) under this technique with improvement in anatomical feature and visual function after the surgery. CONCLUSION: Using this simple yet important technique can provide us the constant intraocular pressure without hypotony and avoid the traditional complicated procedures.

Temporal fluctuations of cardiovascular parameters after intravitreal injections.

BACKGROUND: Despite the effectiveness of intravitreal injection (IVI) of anti-vascular endothelial growth factor in treating retinal diseases, there remains a paucity of evidence on potential systemic risks associated with this procedure. This study aims to investigate cardiovascular parameters and the risk of hypertensive urgency after IVIs. METHODS: Patients who received IVIs for retinal/macular diseases were enrolled retrospectively. Patients who received cataract surgeries were enrolled as controls. Systolic and diastolic blood pressure (BP) and heart rate were measured 10 minutes before, immediately after, and more than 30 minutes after IVIs and cataract surgery. Multivariate analysis was performed to evaluate risk factors for hypertensive urgency. RESULTS: Seventy patients who received IVIs and 95 patients who received cataract surgeries were enrolled. A higher preoperative systolic BP was found in the IVI groups than in the control group (147.0 ± 22.9 vs 136.3 ± 21.8 mmHg, respectively). The patients who received IVIs had a higher increase in perioperative systolic BP immediately after the procedure than the controls (17.43 ± 20.53 mmHg vs 9.11 ± 18.92 mmHg, p = 0.009). The IVI procedure (odds ratio [OR] 4.84, p = 0.008), preoperative systolic BP ≥160 mmHg (OR 17.891, p = 0.001, compared to preoperative systolic BP <140 mmHg), and underlying hypertension (OR 3.305, p = 0.041) were risk factors for hypertensive urgency immediately after the IVIs. CONCLUSION: We found a transient increase in BP after IVIs, which may have been associated with hypertensive urgency and related cardiovascular disorders in older patients and in those with relevant comorbidities. Clinicians should pay more attention to these patients before performing IVIs.

Pluripotent Stem Cells in Clinical Cell Transplantation: Focusing on Induced Pluripotent Stem Cell-Derived RPE Cell Therapy in Age-Related Macular Degeneration.

Human pluripotent stem cells (PSCs), including both embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), represent valuable cell sources to replace diseased or injured tissues in regenerative medicine. iPSCs exhibit the potential for indefinite self-renewal and differentiation into various cell types and can be reprogrammed from somatic tissue that can be easily obtained, paving the way for cell therapy, regenerative medicine, and personalized medicine. Cell therapies using various iPSC-derived cell types are now evolving rapidly for the treatment of clinical diseases, including Parkinson's disease, hematological diseases, cardiomyopathy, osteoarthritis, and retinal diseases. Since the first interventional clinical trial with autologous iPSC-derived retinal pigment epithelial cells (RPEs) for the treatment of age-related macular degeneration (AMD) was accomplished in Japan, several preclinical trials using iPSC suspensions or monolayers have been launched, or are ongoing or completed. The evolution and generation of human leukocyte antigen (HLA)-universal iPSCs may facilitate the clinical application of iPSC-based therapies. Thus, iPSCs hold great promise in the treatment of multiple retinal diseases. The efficacy and adverse effects of iPSC-based retinal therapies should be carefully assessed in ongoing and further clinical trials.

Pseudophakic pupillary block after phacoemulsification and posterior chamber intraocular lens implantation: Cause identification and treatment refinement.

BACKGROUND: Pseudophakic pupillary block (PPB) was rare in patients who undergo phacoemulsification and posterior chamber intraocular lens (PCIOL) implantation. Laser peripheral iridotomy was the most reported but ineffective treatment in the literature. METHODS: Retrospective, interventional case series of patients who developed PPB in Taipei Veterans General Hospital from 2017 to 2021. Clinical course, diagnostic methods, treatment and outcomes were recorded and discussed. RESULTS: Four eyes of three patients were documented. All of them had diabetes and diabetic retinopathy. Anterior segment Optical coherence tomography (OCT) of these patients showed an exudative membrane at the peripapillary area while slit lamp image could not provide a clear view due to the severely edematous corneal condition. Laser peripheral iridotomy and yttrium aluminum garnet (YAG) laser aiming to the peripapillary exudation were applied to break the PPB successfully. CONCLUSION: Diabetes mellitus, intravitreal injection and inflammation are crucial risk factors for PPB. Anterior segment OCT can be a useful diagnostic tool for the detection of the peripapillary exudative membrane while corneal clarity is compromised due to high intraocular pressure. In addition to peripheral laser iridotomy, an effective approach to resolve PPB may be the use of the YAG laser to break the exudative membrane.

Correlations between Clinical and Histopathologic Characteristics in Idiopathic Epiretinal Membrane.

PURPOSE: To investigate correlations between clinical and histopathologic characteristics of idiopathic epiretinal membrane (ERM). DESIGN: Retrospective interventional case series. PARTICIPANTS: In total, 87 eyes from 87 patients with idiopathic ERM who underwent pars plana vitrectomy with peeling of the ERM from 2019 to 2020 were included. METHODS: The outcomes of clinical ophthalmic examination, including measurement of best-corrected visual acuity (BCVA) and spectral-domain OCT (SD-OCT), before and after surgery were reviewed. Surgical specimens were fixed in formalin and embedded in paraffin for histologic and immunohistochemical analysis. MAIN OUTCOMES MEASURES: The association between morphological characteristics revealed on SD-OCT images and the cellular composition of the surgically excised ERM demonstrated with immunohistochemical staining were the main outcome measures. Changes in the BCVA and central macular thickness (CMT) were assessed through a comparison of preoperative and postoperative measurements. RESULTS: Based on SD-OCT morphological characteristics in the foveal area, 15 cases were classified into group 1A (mainly outer retinal thickening), 39 into group 1B (more tenting of the outer retina and distorted inner retina), and 33 into group 1C (prominent inner retina thickening). Overall, postoperative final BCVA and CMT at 1 year improved in all groups. Patients who presented with a better initial BCVA exhibited a more favorable final BCVA. Epiretinal membranes in group 1C demonstrated the greatest decrease in CMT compared with those in groups 1B and 1A, but the final CMT did not differ among the groups. A negative correlation between the density of hyalocytes (P = 0.003) and myofibroblasts (P = 0.047) was noted between the 3 groups. Total cell density and glial cell density of the ERMs were strongly associated with poor final BCVA and BCVA improvement. CONCLUSIONS: The present study provides new histopathologic information regarding the formation and progression of idiopathic ERM. Glial cell proliferation plays a predominant role in these processes. Epiretinal membranes with high cellularity and glial cell density may cause damage to the retina structure, resulting in poor postoperative visual outcomes. These findings provide additional evidence supporting early surgical intervention in patients with idiopathic ERM reported with visual disturbance.

Evaluation of a remote telemedicine platform using a novel handheld fundus camera: Physician and patient perceptions from real-world experience.

BACKGROUND: Although teleophthalmology has gained traction in recent years, it is at the center of the coronavirus disease pandemic. However, most hospitals are not ready owing to a severe lack of real-world experience. Furthermore, a limited number of studies have evaluated telemedicine applications on remote islands. This study aimed to evaluate real-world clinical and referral accuracy, image quality, physician-perceived diagnostic certainty, and patient satisfaction with telemedicine eye screening using a novel handheld fundus camera in a rural and medically underserved population. METHODS: This prospective study included 176 eyes from a remote island. All participants underwent a comprehensive ophthalmic examination. Nonmydriatic retinal images obtained using a handheld fundus camera were reviewed by two retinal specialists to determine image quality, diagnosis, and need for referrals. The agreement of diagnosis between image-based assessments was compared with that of binocular indirect ophthalmoscopic assessments. RESULTS: Image quality of fundus photographs was considered acceptable or ideal in 97.7% and 95.5% of eyes assessed by two reviewers, respectively. There was considerable agreement in diagnosis between the indirect ophthalmoscopic assessment and image-based assessment by two reviewers (Cohen's kappa = 0.80 and 0.78, respectively). Likewise, substantial agreement was achieved in the referrals. The sensitivity for referable retinopathy from the two reviewers was 78% (95% confidence interval [CI], 57%-91%) and 78% (95% CI, 57%-91%), whereas specificity was 99% (95% CI, 95%-99%] and 98% (95% CI, 93%-99%), respectively. For physicians' perceived certainty of diagnosis, 93.8% and 90.3% were considered either certain or reliable. Overall, 97.4% of participants were satisfied with their experiences and greatly valued the telemedicine services. CONCLUSION: Novel fundus camera-based telemedicine screening demonstrated high accuracy in detecting clinically significant retinopathy in real-world settings. It achieved high patient satisfaction and physician-perceived certainty in diagnosis with reliable image quality, which may be scaled internationally to overcome geographical barriers under the global pandemic.

Three-Year Outcomes of Intravitreal Aflibercept Injections for Retinal Angiomatous Proliferation According to Disease Stage.

INTRODUCTION: To evaluate the outcomes of intravitreal aflibercept injections for retinal angiomatous proliferation (RAP) according to disease stage. METHODS: This retrospective chart review included 68 eyes of 53 individuals diagnosed as having RAP and 109 neovascular age-related macular degeneration (nAMD) eyes of 109 patients as controls. All patients received intravitreal injections of aflibercept in a real-world setting. The main outcome measures were the changes in the mean of best-corrected visual acuity (BCVA) and central retinal thickness (CRT) as well as the total number of injections received during the 3-year follow-up period. RESULTS: The average BCVA and CRT changes in eyes affected by RAP and the controls at 3 years were non-significant. Both populations received a similar number of injections. After 3 years of treatment, patients with RAP had visual decline despite stable anatomical outcomes. Approximately 50% of the eyes with stage II RAP exhibited significant BCVA decline at the end of the third year. Among those eyes that had deteriorated BCVA, persistently worsening BCVA and thinning CRT were observed from year 2 to year 3. CONCLUSION: Similar to treating nAMD, intensive injections or aggressive treatment strategies are required to treat RAP to achieve optimal visual outcomes in a real-world setting. The response to aflibercept treatment at the second year is associated with the final visual outcome of eyes with stage II RAP lesions.

Clinical manifestation and current therapeutics in X-juvenile retinoschisis.

X-linked juvenile retinoschisis (XLRS) is one of the common early-onset hereditary retinal degenerative diseases in men. The common symptoms of XLRS range from mild to severe central vision loss and radial stripes created by the fovea, the division of the inner layer of the retina in the peripheral retina and the significant decrease in b-wave amplitude (ERG). Retinoschisin, the 224-amino-acid protein product of the retinoschisis 1 (RS1) gene, contains a discoid domain as the primary structural unit, an N-terminal cleavable signal sequence, and an oligomerization-area component. Retinoschisin is a homo-octamer complex with disulfide links that are released by retinal cells. It helps preserve the retina's integrity by binding to the surface of photoreceptors and bipolar cells. As a recessive genetic disease, XLRS was usually treated by prescribing low vision aids in most clinical cases. A gene replacement therapy based on adeno-associated virus vectors was initiated and showed a breakthrough in treating XLRS in 2014. Understanding the revolution of gene therapy for treating XLRS may accelerate its development and make this gene therapy the template for developing therapeutics against other inherited retinal diseases.

Therapeutic effect of simultaneous intravitreal dexamethasone and aflibercept on diabetic macular edema.

AIMS: To report the effect of simultaneous intravitreal dexamethasone (DEX) and aflibercept for the treatment of diabetic macular edema (DME). METHODS: This retrospective analysis of an open-label, multicenter, consecutive case series included 102 eyes of 81 patients with DME. Patients were selected into two groups. The control group consisted of 50 eyes treated with aflibercept alone, and the combination group consisted of 52 eyes treated with simultaneous DEX implant and aflibercept injection. The primary endpoints were changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline to month 6. The secondary endpoint was the interval of retreatment. RESULTS: Baseline BCVA increased and CRT decreased at 6 months in both groups. Pseudophakic eyes in the combination group exhibited significantly greater BCVA improvement compared with phakic eyes (p = 0.031). Fewer intravitreal treatments were required for eyes treated with combination therapy than for those treated with aflibercept alone (1.56 ± 0.54 vs. 4.04 ± 1.26, p < .0001), with a mean retreatment interval of 3.66 ± 0.69 months. CONCLUSIONS: Simultaneous intravitreal DEX and aflibercept achieved non-inferior improvement of visual and anatomic outcomes compared with aflibercept alone for DME, but exhibited a significantly longer treatment interval and superior visual outcome in pseudophakic eyes. This therapeutic approach is considered a valid strategy for treating DME in the era of COVID-19.

Application of artificial intelligence-driven endoscopic screening and diagnosis of gastric cancer.

The landscape of gastrointestinal endoscopy continues to evolve as new technologies and techniques become available. The advent of image-enhanced and magnifying endoscopies has highlighted the step toward perfecting endoscopic screening and diagnosis of gastric lesions. Simultaneously, with the development of convolutional neural network, artificial intelligence (AI) has made unprecedented breakthroughs in medical imaging, including the ongoing trials of computer-aided detection of colorectal polyps and gastrointestinal bleeding. In the past demi-decade, applications of AI systems in gastric cancer have also emerged. With AI's efficient computational power and learning capacities, endoscopists can improve their diagnostic accuracies and avoid the missing or mischaracterization of gastric neoplastic changes. So far, several AI systems that incorporated both traditional and novel endoscopy technologies have been developed for various purposes, with most systems achieving an accuracy of more than 80%. However, their feasibility, effectiveness, and safety in clinical practice remain to be seen as there have been no clinical trials yet. Nonetheless, AI-assisted endoscopies shed light on more accurate and sensitive ways for early detection, treatment guidance and prognosis prediction of gastric lesions. This review summarizes the current status of various AI applications in gastric cancer and pinpoints directions for future research and clinical practice implementation from a clinical perspective.

Identification of Novel Genomic-Variant Patterns of OR56A5, OR52L1, and CTSD in Retinitis Pigmentosa Patients by Whole-Exome Sequencing.

Inherited retinal dystrophies (IRDs) are rare but highly heterogeneous genetic disorders that affect individuals and families worldwide. However, given its wide variability, its analysis of the driver genes for over 50% of the cases remains unexplored. The present study aims to identify novel driver genes, disease-causing variants, and retinitis pigmentosa (RP)-associated pathways. Using family-based whole-exome sequencing (WES) to identify putative RP-causing rare variants, we identified a total of five potentially pathogenic variants located in genes OR56A5, OR52L1, CTSD, PRF1, KBTBD13, and ATP2B4. Of the variants present in all affected individuals, genes OR56A5, OR52L1, CTSD, KBTBD13, and ATP2B4 present as missense mutations, while PRF1 and CTSD present as frameshift variants. Sanger sequencing confirmed the presence of the novel pathogenic variant PRF1 (c.124_128del) that has not been reported previously. More causal-effect or evidence-based studies will be required to elucidate the precise roles of these SNPs in the RP pathogenesis. Taken together, our findings may allow us to explore the risk variants based on the sequencing data and upgrade the existing variant annotation database in Taiwan. It may help detect specific eye diseases such as retinitis pigmentosa in East Asia.

An Update on Gene Therapy for Inherited Retinal Dystrophy: Experience in Leber Congenital Amaurosis Clinical Trials.

Inherited retinal dystrophies (IRDs) are a group of rare eye diseases caused by gene mutations that result in the degradation of cone and rod photoreceptors or the retinal pigment epithelium. Retinal degradation progress is often irreversible, with clinical manifestations including color or night blindness, peripheral visual defects and subsequent vision loss. Thus, gene therapies that restore functional retinal proteins by either replenishing unmutated genes or truncating mutated genes are needed. Coincidentally, the eye's accessibility and immune-privileged status along with major advances in gene identification and gene delivery systems heralded gene therapies for IRDs. Among these clinical trials, voretigene neparvovec-rzyl (Luxturna), an adeno-associated virus vector-based gene therapy drug, was approved by the FDA for treating patients with confirmed biallelic RPE65 mutation-associated Leber Congenital Amaurosis (LCA) in 2017. This review includes current IRD gene therapy clinical trials and further summarizes preclinical studies and therapeutic strategies for LCA, including adeno-associated virus-based gene augmentation therapy, 11-cis-retinal replacement, RNA-based antisense oligonucleotide therapy and CRISPR-Cas9 gene-editing therapy. Understanding the gene therapy development for LCA may accelerate and predict the potential hurdles of future therapeutics translation. It may also serve as the template for the research and development of treatment for other IRDs.

Xeno-free cryopreservation of adherent retinal pigmented epithelium yields viable and functional cells in vitro and in vivo.

Age-related macular degeneration (AMD) is the primary cause of blindness in adults over 60 years of age, and clinical trials are currently assessing the therapeutic potential of retinal pigmented epithelial (RPE) cell monolayers on implantable scaffolds to treat this disease. However, challenges related to the culture, long-term storage, and long-distance transport of such implants currently limit the widespread use of adherent RPE cells as therapeutics. Here we report a xeno-free protocol to cryopreserve a confluent monolayer of clinical-grade, human embryonic stem cell-derived RPE cells on a parylene scaffold (REPS) that yields viable, polarized, and functional RPE cells post-thaw. Thawed cells exhibit ≥ 95% viability, have morphology, pigmentation, and gene expression characteristic of mature RPE cells, and secrete the neuroprotective protein, pigment epithelium-derived factor (PEDF). Stability under liquid nitrogen (LN2) storage has been confirmed through one year. REPS were administered immediately post-thaw into the subretinal space of a mammalian model, the Royal College of Surgeons (RCS)/nude rat. Implanted REPS were assessed at 30, 60, and 90 days post-implantation, and thawed cells demonstrate survival as an intact monolayer on the parylene scaffold. Furthermore, immunoreactivity for the maturation marker, RPE65, significantly increased over the post-implantation period in vivo, and cells demonstrated functional attributes similar to non-cryopreserved controls. The capacity to cryopreserve adherent cellular therapeutics permits extended storage and stable transport to surgical sites, enabling broad distribution for the treatment of prevalent diseases such as AMD.

Primary Signet Ring Cell/Histiocytoid Carcinoma of the Eyelid: Somatic Mutations in CDH1 and Other Clinically Actionable Mutations Imply Early Use of Targeted Agents.

Primary signet ring cell/histiocytoid carcinoma of the eyelid is a rare ocular malignancy and its diagnosis is often delayed. This neoplasm presents as an insidious, diffusely infiltrative mass in the periocular area that later infiltrates the orbit. An exenteration is usually indicated; however, nearly one-third of patients develop local recurrence or metastasis. Morphologically, it resembles signet ring cell carcinoma of the stomach and breast, raising the possibility of mutations in CDH1, the gene encoding E-cadherin. To determine whether primary signet ring cell/histiocytoid carcinoma harbors the CDH1 mutation or other actionable mutations, we analyzed the tumor tissue via next-generation sequencing. We identified only one case of primary signet ring cell carcinoma of the eyelid with adequate DNA quality for sequencing from the pathological archive during the period 2000 to 2020. A comprehensive evaluation including histopathology, immunohistochemistry, and next-generation sequencing assay was performed on tumor tissue. Immunohistochemically, the tumor exhibited E-cadherin membranous staining with the aberrant cytoplasmic staining of ß-catenin. Using next-generation sequencing, we demonstrated the mutation in the CDH1 gene. In addition, other clinically actionable mutations including ERBB2 and PIK3CA were also detected. The alterations in other actionable genes indicate a need for larger studies to evaluate the pathogenesis and potential therapies for primary signet ring cell/histiocytoid carcinoma of the eyelid.

Recovery of visual field defects following vitrectomy for proliferative diabetic retinopathy: A case report.

RATIONALE: Proliferative diabetic retinopathy (PDR) may lead to severe visual impairment, and visual field (VF) loss in such patients has been reported. Vitrectomy is performed in PDR cases complicated with either vitreous hemorrhage or tractional retinal detachment to restore their visual acuity. However, its effect on VF defects is limited in data. Herein, we report the recovery of VF defects following vitrectomy in a patient with PDR. PATIENT CONCERNS: A 25-year-old female with bilateral PDR and vitreous hemorrhage received 2 monthly intravitreal injections of aflibercept in both eyes. Six months after her last injection, she presented with fibrovascular membrane formation in both eyes and VF defects of -9.02 dB and -20.05 dB in the right and left eye, respectively. DIAGNOSES: Proliferative diabetic retinopathy in both eyes. INTERVENTIONS: The patient underwent vitrectomy for her left eye. OUTCOMES: Although her visual acuity did not improve as expected, results from the Humphrey visual field analyzer showed notably improvement of her left eye (-9.05 dB) after the surgery. LESSONS: Vitrectomy potentially allows recovery of VF defects in patients with PDR.

Smartphone-based diabetic macula edema screening with an offline artificial intelligence.

BACKGROUND: Diabetic macular edema (DME) is a sight-threatening condition that needs regular examinations and remedies. Optical coherence tomography (OCT) is the most common used examination to evaluate the structure and thickness of the macula, but the software in the OCT machine does not tell the clinicians whether DME exists directly. Recently, artificial intelligence (AI) is expected to aid in diagnosis generation and therapy selection. We thus develop a smartphone-based offline AI system that provides diagnostic suggestions and medical strategies through analyzing OCT images from diabetic patients at the risk of developing DME. METHODS: DME patients receiving treatments in 2017 at Taipei Veterans General Hospital were included in this study. We retrospectively collected the OCT images of these patients from January 2008 to July 2018. We established the AI model based on MobileNet architecture to classify the OCT images conditions. The confusion matrix has been applied to present the performance of the trained AI model. RESULTS: Based on the convolutional neural network with the MobileNet model, our AI system achieved a high DME diagnostic accuracy of 90.02%, which is comparable to other AI systems such as InceptionV3 and VGG16. We further developed a mobile-application based on this AI model available at https://aicl.ddns.net/DME.apk. CONCLUSION: We successful integrated an AI model into the mobile device to provide an offline method to provide the diagnosis for quickly screening the risk of developing DME. With the offline property, our model could help those nonophthalmological healthcare providers in offshore islands or underdeveloped countries.