Genetic associations of central serous chorioretinopathy subtypes, neovascular age-related macular degeneration, and polypoidal choroidal vasculopathy.

PURPOSE: To evaluate the genetic associations of different subtypes of central serous chorioretinopathy (CSCR), neovascular age-related macular degeneration (nAMD), and polypoidal choroidal vasculopathy (PCV). DESIGN: A case-control genetic association study. METHODS: This study enrolled 217 CSCR, 341 nAMD, 288 PCV patients, and 1380 controls. The CSCR patients were classified into those with focal or diffuse leakage, with or without pigment epithelial detachment (PED), and with or without macular neovascularization (MNV). Associations between 11 variants from 8 genes, ADAMTS9, ANGPT2, ARMS2, CFH, NR3C2, PGF, TNFRSF10A and VIPR2, and diseases/subtypes were analyzed by logistic regression analysis adjusted for age and sex, and inter-phenotype comparison by heterogeneity test. RESULTS: The CFH rs800292-A conferred a protective effect for CSCR with MNV (OR=0.44, P = 0.002) and a risk effect for CSCR without MNV (OR=1.31, P = 0.023). CSCR patients carrying rs800292-G had a 3.23-fold of increased risk towards developing secondary MNV (P = 1.45 ×10-4). CFH rs3753394, rs800292 and rs1329428 showed similar effects among CSCR with MNV, nAMD and PCV, but opposite effects on CSCR without MNV. TNFRSF10A rs13278062-T was associated with overall CSCR but not with CSCR subtypes, nAMD or PCV. Moreover, CFH and ARMS2 SNPs showed heterogeneous effects in CSCR without MNV against CSCR with MNV, nAMD and PCV. CONCLUSIONS: Genetic associations of CSCR with MNV resembled nAMD and PCV compared to CSCR without MNV, indicating differential genetic effects on neovascularization and choroidopathy. Further investigation of the functional roles of CFH, ARMS2, and TNFRSF10A in CSCR, nAMD and PCV should help elucidate the mechanisms of these maculopathies.

Diffuse Jejunal Lipomatosis and Associated Complications.

Small intestinal lipomatosis is a rare condition with a poorly understood epidemiology and pathophysiology. Cases of small intestinal lipomatosis have been documented in multiple countries over the last century, yet little has been published regarding the natural history of this disease. Therapeutic options are largely surgical and based on limited evidence. We report a unique case of diffuse jejunal lipomatosis in a 62-year-old man with complications of small bowel obstruction, small bowel volvulus, jejunal diverticulosis, pneumatosis intestinalis, malnutrition, small intestinal bacterial overgrowth, and intestinal dysmotility developing over a 12-year period.

Emerging Roles of cGAS-STING Signaling in Mediating Ocular Inflammation.

Cyclic GMP-AMP (cGAMP) synthase (cGAS), a sensor of cytosolic DNA, recognizes cytoplasmic nucleic acids to activate the innate immune responses via generation of the second messenger cGAMP and subsequent activation of the stimulator of interferon genes (STINGs). The cGAS-STING signaling has multiple immunologic and physiological functions in all human vital organs. It mediates protective innate immune defense against DNA-containing pathogen infection, confers intrinsic antitumor immunity via detecting tumor-derived DNA, and gives rise to autoimmune and inflammatory diseases upon aberrant activation by cytosolic leakage of self-genomic and mitochondrial DNA. Disruptions in these functions are associated with the pathophysiology of various immunologic and neurodegenerative diseases. Recent evidence indicates important roles of the cGAS-STING signaling in mediating inflammatory responses in ocular inflammatory and inflammation-associated diseases, such as keratitis, diabetic retinopathy, age-related macular degeneration, and uveitis. In this review, we summarize the recently emerging evidence of cGAS-STING signaling in mediating ocular inflammatory responses and affecting pathogenesis of these complex eye diseases. We attempt to provide insightful perspectives on future directions of investigating cGAS-STING signaling in ocular inflammation. Understanding how cGAS-STING signaling is modulated to mediate ocular inflammatory responses would allow future development of novel therapeutic strategies to treat ocular inflammation and autoimmunity.

Cost-effectiveness of virtual reality and wet laboratory cataract surgery simulation.

PURPOSE: To evaluate the cost-effectiveness of phacoemulsification simulation training in virtual reality simulator and wet laboratory on operating theater performance. METHODS: Residents were randomized to a combination of virtual reality and wet laboratory phacoemulsification or wet laboratory phacoemulsification. A reference control group consisted of trainees who had wet laboratory training without phacoemulsification. All trainees were assessed on operating theater performance in 3 sequential cataract patients. International Council of Ophthalmology Surgical Competency Assessment Rubric-phacoemulsification (ICO OSCAR phaco) scores by 2 masked independent graders and cost data were used to determine the incremental cost-effectiveness ratio (ICER). A decision model was constructed to indicate the most cost-effective simulation training strategy based on the willingness to pay (WTP) per ICO OSCAR phaco score gained. RESULTS: Twenty-two trainees who performed phacoemulsification in 66 patients were analyzed. Trainees who had additional virtual reality simulation achieved higher mean ICO OSCAR phaco scores compared with trainees who had wet laboratory phacoemulsification and control (49.5 ± standard deviation [SD] 9.8 vs 39.0 ± 15.8 vs 32.5 ± 12.1, P < .001). Compared with the control group, ICER per ICO OSCAR phaco of wet laboratory phacoemulsification was $13,473 for capital cost and $2209 for recurring cost. Compared with wet laboratory phacoemulsification, ICER per ICO OSCAR phaco of additional virtual reality simulator training was US $23,778 for capital cost and $1879 for recurring cost. The threshold WTP values per ICO OSCAR phaco score for combined virtual reality simulator and wet laboratory phacoemulsification to be most cost-effective was $22,500 for capital cost and $1850 for recurring cost. CONCLUSIONS: Combining virtual reality simulator with wet laboratory phacoemulsification training is effective for skills transfer in the operating theater. Despite of the high capital cost of virtual reality simulator, its relatively low recurring cost is more favorable toward cost-effectiveness.

Guideline No. 437: Diagnosis and Management of Adenomyosis.

OBJECTIVE: To describe the current evidence-based diagnosis and management of adenomyosis. TARGET POPULATION: All patients with a uterus of reproductive age. OPTIONS: Diagnostic options include transvaginal sonography and magnetic resonance imaging. Treatment options should be tailored to symptoms (heavy menstrual bleeding, pain, and/or infertility) and include medical options (non-steroidal anti-inflammatory drugs, tranexamic acid, combined oral contraceptives, levonorgestrel intrauterine system, dienogest, other progestins, gonadotropin-releasing analogues), interventional options (uterine artery embolization), and surgical options (endometrial ablation, excision of adenomyosis, hysterectomy). OUTCOMES: Outcomes of interest include reduction in heavy menstrual bleeding, reduction in pelvic pain (dysmenorrhea, dyspareunia, chronic pelvic pain), and improvement in reproductive outcomes (fertility, miscarriage, adverse pregnancy outcomes). BENEFITS, HARMS, AND COSTS: This guideline will benefit patients with gynaecological complaints that may be caused by adenomyosis, especially those patients who wish to preserve their fertility, by presenting diagnostic methods and management options. It will also benefit practitioners by improving their knowledge of various options. EVIDENCE: Databases searched were MEDLINE Reviews, MEDLINE ALL, Cochrane, PubMed, EMBASE. The initial search was completed in 2021 and updated with relevant articles in 2022. Search terms included adenomyosis, adenomyoses, endometritis (used/indexed as adenomyosis before 2012), (endometrium AND myometrium) uterine adenomyosis/es, symptom/s/matic adenomyosis] AND [diagnosis, symptoms, treatment, guideline, outcome, management, imaging, sonography, pathogenesis, fertility, infertility, therapy, histology, ultrasound, review, meta-analysis, evaluation]. Articles included randomized controlled trials, meta-analyses, systematic reviews, observational studies, and case reports. Articles in all languages were searched and reviewed. VALIDATION METHODS: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Table A1 for definitions and Table A2 for interpretations of strong and conditional [weak] recommendations). INTENDED AUDIENCE: Obstetrician-gynaecologists, radiologists, family physicians, emergency physicians, midwives, registered nurses, nurse practitioners, medical students, residents, and fellows. TWEETABLE ABSTRACT: Adenomyosis is common in reproductive-aged women. There are diagnostic and management options that preserve fertility available. SUMMARY STATEMENTS: RECOMMENDATIONS.

Directive clinique no 437 : Diagnostic et prise en charge de l'adénomyose.

OBJECTIF: Décrire les pratiques actuelles fondées sur des données probantes pour le diagnostic et la prise en charge de l'adénomyose. POPULATION CIBLE: Toutes les patientes en âge de procréer qui ont un utérus. OPTIONS: Les options diagnostiques sont l'échographie endovaginale et l'imagerie par résonance magnétique. Les options thérapeutiques doivent être adaptées aux symptômes (saignements menstruels abondants, douleur et/ou infertilité) et comprendre des options médicamenteuses (anti-inflammatoires non stéroïdiens, acide tranexamique, contraceptifs oraux combinés, système intra-utérin à libération de lévonorgestrel, diénogest, autres progestatifs, analogues de la gonadotrophine), des options interventionnelles (embolisation de l'artère utérine) et des options chirurgicales (ablation de l'endomètre, excision de l'adénomyose, hystérectomie). RéSULTATS: Les critères de jugement sont la réduction des saignements menstruels abondants, l'atténuation de la douleur pelvienne (dysménorrhée, dyspareunie, douleur pelvienne chronique) et l'amélioration du devenir reproductif (fertilité, avortement spontané, issues de grossesse défavorables). BéNéFICES, RISQUES ET COûTS: Par la présentation des méthodes de diagnostic et des options de prise en charge, cette directive sera bénéfique pour les patientes qui expriment des plaintes de nature gynécologique potentiellement causées par l'adénomyose, en particulier celles qui souhaitent préserver leur fertilité. La directive sera également utile aux praticiens qui pourront améliorer leurs connaissances sur les différentes options. DONNéES PROBANTES: Des recherches ont été effectuées dans les bases de données MEDLINE Reviews, MEDLINE ALL, Cochrane, PubMed et Embase. La recherche initiale a été réalisée en 2021 et mise à jour avec les articles pertinents en 2022. Les termes de recherche utilisés sont les suivants : adenomyosis, adenomyoses, endometritis (utilisés ou indexés sous adenomyosis avant 2012), (endometrium AND myometrium) uterine adenomyosis/es, symptom/s/matic adenomyosis ET [diagnosis, symptoms, treatment, guideline, outcome, management, imaging, sonography, pathogenesis, fertility, infertility, therapy, histology, ultrasound, review, meta-analysis, evaluation]. Les articles retenus sont des essais cliniques randomisés, des méta-analyses, des revues systématiques, des études observationnelles et des études de cas. Des articles dans toutes les langues ont été répertoriés et examinés. MéTHODES DE VALIDATION: Les auteurs ont évalué la qualité des données probantes et la force des recommandations en utilisant le cadre méthodologique GRADE (Grading of Recommendations Assessment, Development and Evaluation). Voir l'annexe A en ligne (Tableau A1 pour les définitions et Tableau A2 pour l'interprétation des recommandations fortes et conditionnelles [faibles]). PROFESSIONNELS CONCERNéS: Obstétriciens-gynécologues, radiologistes, médecins de famille, urgentologues, sages-femmes, infirmières autorisées, infirmières praticiennes, étudiants en médecine, résidents et moniteurs cliniques (fellows). RéSUMé POUR TWITTER: L'adénomyose est fréquemment observée chez les femmes en âge de procréer. Il existe des options de diagnostic et de prise en charge qui préservent la fertilité. DÉCLARATIONS SOMMAIRES: RECOMMANDATIONS.

Impact Comparison of El Niño and Ageing Crops on Malaysian Oil Palm Yield.

Ageing oil palm crops show a significant correlation with the declining oil palm yield in Malaysia. Not only do aged crops result in lower production, but they are also more costly and difficult to harvest. The Malaysian oil palm yield recovered to the pre-El Niño level after the 1997/98 El Niño event. However, the oil palm yield failed to recover after the recent 2015/16 El Niño. Due to the accumulation of aged oil palm plantations in Malaysia, the financial losses from different magnitudes of El Niño events are increasing. Thirty-four years of monthly oil palm yield trends in Malaysia were compared with the El Niño-free yield dataset to show that the oil palm yield downtrend pattern is the same with or without El Niño events in Malaysia for the most recent 15 years (2005 to 2019). The performance of oil palm yield did not show any significant difference from 2000 to 2019. This study estimates that ageing oil palms would lead to a minimum opportunity loss of USD 431 million by December 2022. Without a proper replanting program, the total combined loss attributable to the ageing crops from 2009 to 2022 is estimated to be USD 3.94 billion, which is more profound than losses due to El Niño events within the same period. This study also concluded that a continuous 7-year replanting scheme of at least 115,000 hectares per year is needed to address the adverse impact of ageing crops on the Malaysian oil palm yield, which accounts for nearly 30% of the global palm oil production.

Optimizing treatment for diabetic macular edema during cataract surgery.

Diabetic macular edema (DME) causes visual impairment in diabetic retinopathy (DR). Diabetes mellitus is a global epidemic and diabetic individuals are at risk of developing DR. Approximately 1 in 10 diabetic patients suffers from DME, which is the commonest cause of vision-threatening DR at primary-care screening. Furthermore, diabetes predisposes to a higher frequency and a younger onset of cataract, which further threatens vision in DME patients. Although cataract extraction is an effective cure, vision may still deteriorate following cataract surgery due to DME progression or recurrence, of which the risks are significantly higher than for patients without concurrent or previous history of DME at the time of operation. The management of pre-existing DME with visually significant cataract is a clinical conundrum. Deferring cataract surgery until DME is adequately treated is not ideal because of prolonged visual impairment and maturation of cataract jeopardizing surgical safety and monitoring of DR. On the other hand, the progression or recurrence of DME following prompt cataract surgery is a profound disappointment for patients and ophthalmic surgeons who had high expectations for postoperative visual improvement. Prescription of perioperative anti-inflammatory eye drops is effective in lowering the risk of new-onset DME after cataract surgery. However, management of concurrent DME at the time of cataract surgery is much more challenging because DME is unlikely to resolve spontaneously even with the aid of anti-inflammatory non-steroidal or steroid eye drops. A number of clinical trials using intravitreal injection of corticosteroids and anti-vascular endothelial growth factor (anti-VEGF) as first-line therapy have demonstrated safety and efficacy to treat DME. These drugs have also been administered perioperatively for the prevention of DME worsening in patients undergoing cataract surgery. This article reviews the scientific evidence to guide ophthalmologists on the efficacy and safety of various therapies for managing patients with DME who are particularly vulnerable to cataract surgery-induced inflammation, which disintegrates the blood-retinal barrier and egression of fluid in macular edema.

Recent Advances in Clinical Applications of Imaging in Retinal Diseases.

Many diseases that cause visual impairment, as well as systemic conditions, manifest in the posterior segment of the eye. With the advent of high-speed, high-resolution, reliable, and noninvasive imaging techniques, ophthalmologists are becoming more dependent on ocular imaging for disease diagnosis, classification, and management in clinical practice. There are rapid advances on the indications of multimodal retinal imaging techniques, including the application of ultra-widefield fundus angiography, fundus autofluorescence, optical coherence tomography, as well as optical coherence tomography angiography. This review summarizes and highlights the clinical applications, latest indications, and interpretations of multimodal imaging in age-related macular degeneration, polypoidal choroidal vasculopathy, diabetic macular edema, central serous chorioretinopathy, diabetic retinopathy, retinal vein occlusion, and uveitis.

Epigallocatechin-3-Gallate Protects Trabecular Meshwork Cells from Endoplasmic Reticulum Stress.

Primary open-angle glaucoma (POAG) is the most common form of glaucoma, for which elevated intraocular pressure (IOP) is a major risk factor. IOP is mainly regulated by dynamic balance of aqueous humor (AH) production and outflow via the conventional trabecular meshwork/Schlemm's canal (TM/SC) pathway. Dysfunctions of TM cells due to endoplasmic reticulum (ER) stress have been demonstrated to increase the resistance of AH outflow, resulting in IOP elevation. Epigallocatechin-3-gallate (EGCG), the most abundant polyphenolic component in green tea, has been shown to alleviate ER stress in several diseases while its potential roles in alleviating ER stress in TM cells have not been determined. In this study, we investigate the mitigation of tunicamycin-induced ER stress in TM cells by EGCG. MTT assay was used to measure the cell viability of human TM (HTM) cells and primary porcine TM (PTM) cells. ER stress levels in both HTM cells and primary PTM cells were detected by quantitative real-time PCR. The primary PTM cells isolated from porcine TM tissues were characterized by immunostaining. We found that 40 µM and 80 µM EGCG pretreatment substantially promoted HTM cell survival under 3 µM tunicamycin-induced ER stress. Pretreatment of 40 µM EGCG markedly reduced the expression of ER stress markers ATF4, HSPA5, and DDIT3, evoked by 3 µM tunicamycin in HTM cells. Furthermore, 40 µM EGCG pretreatment significantly decreased the expressions of ATF4, HSPA5, and DDIT3 at the mRNA level induced by 3 µM tunicamycin and improved cell viability in primary PTM cells. Our results show that EGCG is capable of protecting TM cells from ER stress. EGCG provides a promising therapeutic option for POAG treatment.

Post-translational modifications on the retinoblastoma protein.

The retinoblastoma protein (pRb) functions as a cell cycle regulator controlling G1 to S phase transition and plays critical roles in tumour suppression. It is frequently inactivated in various tumours. The functions of pRb are tightly regulated, where post-translational modifications (PTMs) play crucial roles, including phosphorylation, ubiquitination, SUMOylation, acetylation and methylation. Most PTMs on pRb are reversible and can be detected in non-cancerous cells, playing an important role in cell cycle regulation, cell survival and differentiation. Conversely, altered PTMs on pRb can give rise to anomalies in cell proliferation and tumourigenesis. In this review, we first summarize recent findings pertinent to how individual PTMs impinge on pRb functions. As many of these PTMs on pRb were published as individual articles, we also provide insights on the coordination, either collaborations and/or competitions, of the same or different types of PTMs on pRb. Having a better understanding of how pRb is post-translationally modulated should pave the way for developing novel and specific therapeutic strategies to treat various human diseases.

Genetic associations of central serous chorioretinopathy: a systematic review and meta-analysis.

AIMS: To identify single-nucleotide polymorphisms (SNPs) associated with central serous chorioretinopathy (CSCR) by a systematic review and meta-analysis, and to compare the association profiles between CSCR, neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV). METHODS: We searched the EMBASE, PubMed and Web of Science for genetic studies of CSCR from the starting dates of the databases to 12 September 2020. We then performed meta-analyses on all SNPs reported by more than two studies and calculated the pooled OR and 95% CIs. We also conducted sensitivity analysis and adopted the funnel plot to assess potential publication bias. RESULTS: Totally 415 publications were reviewed, among them 10 were eligible for meta-analysis. We found 10 SNPs that have been reported at least twice. Meta-analysis and sensitivity analysis confirmed significant associations between CSCR and six SNPs in three genes, namely age-related maculopathy susceptibility 2 (ARMS2) (rs10490924, OR=1.37; p=0.00064), complement factor H (CFH) (rs800292, OR=1.44; p=7.80×10-5; rs1061170, OR=1.34; p=0.0028; rs1329428, OR=1.40; p=0.012; and rs2284664, OR=1.36; p=0.0089) and tumour necrosis factor receptor superfamily, member 10a (TNFRSF10A) (rs13278062, OR=1.34; p=1.44×10-15). Among them, only TNFRSF10A rs13278062 showed the same trend of effect on CSCR, nAMD and PCV, while the SNPs in ARMS2 and CFH showed opposite trends in the SNP associations. CONCLUSIONS: This study confirmed the associations of ARMS2, CFH and TNFRSF10A with CSCR, and revealed that ARMS2, CFH and TNFRSF10A may affect different phenotypic expressions of CSCR, nAMD and PCV.

Safety review of anti-VEGF therapy in patients with myopic choroidal neovascularization.

INTRODUCTION: Anti-angiogenesis therapy with intravitreal anti-VEGF agents is now the standard-of-care treatment for myopic choroidal neovascularization (CNV). AREAS COVERED: We provide a critical review of the safety of all the anti-VEGF agents currently used for treating myopic CNV including ranibizumab, aflibercept, conbercept, bevacizumab, and ziv-aflibercept. EXPERT OPINION: Anti-VEGF therapy for myopic CNV with the currently available anti-VEGF drugs generally have favorable safety outcomes in the short-term. Nonetheless, ocular adverse events following anti-VEGF therapy for myopic CNV may develop and these include worsening or new development of myopic traction maculopathy, increased risk of retinal detachment, and progression of chorioretinal atrophy. Clinicians should be aware of these potential complications and evaluate them before and after anti-VEGF therapy.

A Multitask Deep-Learning System to Classify Diabetic Macular Edema for Different Optical Coherence Tomography Devices: A Multicenter Analysis.

OBJECTIVE: Diabetic macular edema (DME) is the primary cause of vision loss among individuals with diabetes mellitus (DM). We developed, validated, and tested a deep learning (DL) system for classifying DME using images from three common commercially available optical coherence tomography (OCT) devices. RESEARCH DESIGN AND METHODS: We trained and validated two versions of a multitask convolution neural network (CNN) to classify DME (center-involved DME [CI-DME], non-CI-DME, or absence of DME) using three-dimensional (3D) volume scans and 2D B-scans, respectively. For both 3D and 2D CNNs, we used the residual network (ResNet) as the backbone. For the 3D CNN, we used a 3D version of ResNet-34 with the last fully connected layer removed as the feature extraction module. A total of 73,746 OCT images were used for training and primary validation. External testing was performed using 26,981 images across seven independent data sets from Singapore, Hong Kong, the U.S., China, and Australia. RESULTS: In classifying the presence or absence of DME, the DL system achieved area under the receiver operating characteristic curves (AUROCs) of 0.937 (95% CI 0.920-0.954), 0.958 (0.930-0.977), and 0.965 (0.948-0.977) for the primary data set obtained from CIRRUS, SPECTRALIS, and Triton OCTs, respectively, in addition to AUROCs >0.906 for the external data sets. For further classification of the CI-DME and non-CI-DME subgroups, the AUROCs were 0.968 (0.940-0.995), 0.951 (0.898-0.982), and 0.975 (0.947-0.991) for the primary data set and >0.894 for the external data sets. CONCLUSIONS: We demonstrated excellent performance with a DL system for the automated classification of DME, highlighting its potential as a promising second-line screening tool for patients with DM, which may potentially create a more effective triaging mechanism to eye clinics.

Metastatic pancreatic cancer with complete response to FOLFIRINOX treatment.

A 59-year-old woman presented with abdominal pain associated with nausea and night sweats. A large mass was found in the pancreatic tail and innumerable liver lesions were identified. Ultrasound-guided biopsy of a liver nodule confirmed moderately differentiated adenocarcinoma consistent with a pancreatobiliary primary. On FOLFIRINOX chemotherapy, subsequent CT scans showed shrinkage of the pancreatic mass and liver metastases. Her cancer antigen 19-9 (CA 19-9) normalised after 11 months. Oxaliplatin was discontinued due to peripheral neuropathy but she completed 37 cycles of FOLFIRI during which her pancreatic mass disappeared, liver lesions decreased in size and were subsequently deemed to be scar tissue by the radiologist. After 4 years of treatment, the patient agreed to a break from chemotherapy. Eighteen months afterwards, an MRI abdomen continues to demonstrate no visible pancreatic mass and the two remaining liver lesions, believed to be scar tissue, remain stable. Her CA 19-9 level remains normal. This appears to be a complete response to FOLFIRINOX/FOLFIRI chemotherapy in a patient with metastatic pancreatic cancer.

Analysis of choriocapillaris perfusion and choroidal layer changes in patients with chronic central serous chorioretinopathy randomised to micropulse laser or photodynamic therapy.

PURPOSE: The purpose of this study was to investigate the signal changes in choriocapillaris flow deficits and choroidal thickness changes using swept-source optical coherence tomography angiography (OCTA) following different treatments. DESIGN: A double-blind, randomised controlled trial. METHODS: Patients with unilateral chronic central serous chorioretinopathy (CSC) were randomised to receive subthreshold micropulse laser therapy (MLT) or half-dose photodynamic therapy (PDT). Choroidal thickness and choriocapillaris flow deficit signals were investigated. RESULTS: Eighteen patients were randomised into the MLT group and 15 patients into the PDT group. Areas with flow deficit signals were identified in all baseline OCTA images of the choriocapillaris, with mean areas of 0.420 and 0.465 mm2 in the MLT and PDT groups, respectively. These flow deficit signal areas were significantly reduced at 6 months (p=0.011) in the MLT group and at 3 months (p=0.008) in the PDT group. Patients from the PDT group were shown to have smaller flow deficit areas than patients from the MLT group at all time points after treatment (p=0.001, analyses of variance). The mean choroidal volume of the fovea showed a significant reduction at 1 month (p=0.003), 3 months (p=0.199) and 6 months (p=0.006) in the PDT group. CONCLUSION: The flow deficit areas identified in the choriocapillaris layer may suggest possible relative choroidal ischaemia. With measurement of choroidal volume reduction and faster rates of flow deficit area change, PDT has a stronger effect than MLT in promoting choriocapillaris recovery.

Ranibizumab for myopic choroidal neovascularization.

INTRODUCTION: Myopic choroidal neovascularization (CNV) is one of the most vision-threatening complications in patients with pathologic myopia. Over the last decade, anti-angiogenesis therapy with anti-vascular endothelial growth factor (anti-VEGF) agents has become the standard-of-care treatment for myopic CNV and ranibizumab has been approved for treating myopic CNV. AREAS COVERED: Review of preclinical studies and clinical trials data supporting the use of ranibizumab for myopic CNV. Discussion on the mechanisms, efficacy, safety, regulatory affairs, and future directions of ranibizumab for myopic CNV are highlighted. EXPERT OPINION: Ranibizumab has demonstrated good efficacy and safety profile in multiple clinical trials and long-term studies for treating myopic CNV. Cost-effective analysis has shown that ranibizumab therapy is a cost-effective treatment for myopic CNV. Among the currently available anti-VEGF agents, ranibizumab is the only drug that is approved for the treatment of myopic CNV by the US Food and Drug Administration. In the coming few years, biosimilars of ranibizumab may become available and will have the potential to lower the cost of ranibizumab. Long-term visual gain after ranibizumab treatment for myopic CNV is limited by chorioretinal atrophy associated with pathologic myopia and further research is required to tackle the development of chorioretinal atrophy.

OCT Angiography Metrics Predict Progression of Diabetic Retinopathy and Development of Diabetic Macular Edema: A Prospective Study.

PURPOSE: To prospectively determine the relationship of OCT angiography (OCTA) metrics to diabetic retinopathy (DR) progression and development of diabetic macular edema (DME). DESIGN: Prospective, observational study. PARTICIPANTS: A total of 205 eyes from 129 patients with diabetes mellitus followed up for at least 2 years. METHODS: All participants underwent OCTA with a swept-source OCT device (DRI-OCT Triton, Topcon, Inc, Tokyo, Japan). Individual OCTA images of superficial capillary plexus (SCP) and deep capillary plexus (DCP) were generated by IMAGEnet6 (Basic License 10). After a quality check, automated measurements of foveal avascular zone (FAZ) area, FAZ circularity, vessel density (VD), and fractal dimension (FD) of both SCP and DCP were then obtained. MAIN OUTCOME MEASURES: Progression of DR and development of DME. RESULTS: Over a median follow-up of 27.14 months (interquartile range, 24.16-30.41 months), 28 of the 205 eyes (13.66%) developed DR progression. Of the 194 eyes without DME at baseline, 17 (8.76%) developed DME. Larger FAZ area (hazard ratio [HR], 1.829 per SD increase; 95% confidence interval [CI], 1.332-2.512), lower VD (HR, 1.908 per SD decrease; 95% CI, 1.303-2.793), and lower FD (HR, 4.464 per SD decrease; 95% CI, 1.337-14.903) of DCP were significantly associated with DR progression after adjusting for established risk factors (DR severity, glycated hemoglobin, duration of diabetes, age, and mean arterial blood pressure at baseline). Lower VD of SCP (HR, 1.789 per SD decrease; 95% CI, 1.027-4.512) was associated with DME development. Compared with the model with established risk factors alone, the addition of OCTA metrics improved the predictive discrimination of DR progression (FAZ area of DCP, C-statistics 0.723 vs. 0.677, P < 0.001; VD of DCP, C-statistics 0.727 vs. 0.677, P = 0.001; FD of DCP, C-statistics 0.738 vs. 0.677, P < 0.001) and DME development (VD of SCP, C-statistics 0.904 vs. 0.875, P = 0.036). CONCLUSIONS: The FAZ area, VD, and FD of DCP predict DR progression, whereas VD of SCP predicts DME development. Our findings provide evidence to support that OCTA metrics improve the evaluation of risk of DR progression and DME development beyond traditional risk factors.