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.

Visualising the choriocapillaris: Histology, imaging modalities and clinical research - A review.

The choriocapillaris plays a considerable role in the normal physiology of the eye as well as in various diseases. Assessing the changes in the choriocapillaris can therefore provide important information about normal ageing and pathogenesis of visual impairment, and even some systemic diseases. In vivo imaging of the choriocapillaris has evolved from non-depth resolved, dye-based angiography to advanced, high-resolution optical coherence tomography angiography (OCTA). However, the intricate microvascular networks within the choriocapillaris are still beyond the resolving limits of most OCTA instruments. Knowledge of histology, meticulous image acquisition methods, recognition of artefact and post-acquisition processing techniques are necessary for optimising OCTA choriocapillaris images. Qualitative and quantitative analyses of the choriocapillaris provide clinical information in age-related macular degeneration (AMD), diabetic retinopathy (DR), pathologic myopia and central serous chorioretinopathy (CSC). Furthermore, studies have revealed choriocapillaris changes in posterior uveitis that are correlated with treatment outcome and have important prognostic significance. In addition to retinal diseases, choriocapillaris changes have been observed in systemic vascular diseases and complications associated with pregnancy.

Choroidal structures in polypoidal choroidal vasculopathy, neovascular age-related maculopathy, and healthy eyes determined by binarization of swept source optical coherence tomographic images.

PURPOSE: To evaluate quantitatively the choroidal vascularity in polypoidal choroidal vasculopathy (PCV) and neovascular age-related macular degeneration (AMD) patients compared to healthy controls. METHODS: All eyes underwent swept source optical coherence tomography (OCT), and choroidal images were binarized into blood vessels lumen and stroma. The choroidal vascular index (CVI) was defined as the ratio of luminal area (LA) over total choroidal area of the subfoveal region with a width of 1500 µm. RESULTS: The study included 73 patients with neovascular AMD or PCV with mean ± standard deviation (SD) age of 71.8 ± 9.3 years, which was older than the mean age of 65.1 ± 10.8 years of 72 healthy eyes from control group (p < 0.01). The 44 PCV eyes had significantly higher mean SFCT of 214.23 ± 95.21 µm than neovascular AMD eyes (172.74 ± 96.48 µm, p = 0.03) and greater luminal area (0.23 ± 0.09 mm2 vs. 0.19 ± 0.08 mm2, p = 0.05). After adjusting for age, axial length, and gender in multivariate regression analysis, the SFCT of PCV and neovascular AMD eyes were not significantly different from healthy eyes (195.55 ± 93.11 µm), but the CVI of both PCV (64.94 ± 5.43%, p = 0.01) and neovascular AMD (62.54 ± 5.57%, p = <0.01) were significantly lower than control (68.53 ± 5.91%). CONCLUSION: Despite physiological changes of choroidal vasculature due to aging, the choroidal morphology is different in PCV, neovascular AMD and healthy eyes, which has implication on disease pathogenesis.

Techniques to minimize skin incision scar for external dacryocystorhinostomy.

Although there has been a narrowing in the gap in successful functional outcomes between external and endonasal DCR, external DCR is still being frequently performed when cost, availability of additional surgical instruments and visual systems, surgeon's experience and preference are concerned. Nonetheless, skin incisions at the lateral nasal sidewall of the lower eyelid inevitably leave cutaneous scars. The purpose of this review is to evaluate the outcomes of current modified surgical practices that prevent a conspicuous scar in external DCR.

Endoscopic-assisted retrieval of retained lacrimal stent material in congenital nasolacrimal duct obstruction without dacryocystorhinostomy.

We report a 3-year-old child with history of congenital nasolacrimal duct obstruction who failed lacrimal probing and underwent bicanalicular intubation. Removal of stent from the superior punctum was unsuccessful and it was trapped in the lacrimal sac. We performed endonasal endoscopic-assisted retrieval of retained stent material without necessitating dacryocystorhinostomy (DCR). There was no recurrence of infection and nasolacrimal duct obstruction symptoms during 6 months of follow-up.

Aesthetic assessment in periciliary "v-incision" versus conventional external dacryocystorhinostomy in Asians.

PURPOSE: To determine the functional and aesthetic outcomes of periciliary "v-incision" external dacryocystorhinostomy (DCR) and to compare with conventional approach. METHOD: Charts review of consecutive cases of "v-incision" (VDCR) or conventional DCR performed in a single institute, between January 2007 and March 2014. All procedures were performed or supervised by a single surgeon. Two periciliary incisions were made near the skin-mucosal junction at the upper and lower eyelid margins medial to the punctum joining at the medial canthal angle to form a "v" shape. Subcutaneous dissection was carried out inferomedially to reach the anterior lacrimal crest. DCR was then performed in the usual manner. Functional success was defined as no persistent or recurrent epiphora and patency on irrigation of the lacrimal drainage system at least 6 months post-surgery. A cross-sectional aesthetic survey was conducted by asking the patients to rate their scar appearance satisfaction on a visual analogue scale (VAS). External photographs were graded by two independent, masked physicians using VAS as well as the Stony Brook scar evaluation scale (SBSES). RESULTS: Sixty-one patients with median age of 64 years met the inclusion criteria, with median follow-up duration of 28 months. Thirty-eight eyes underwent VDCR, and 23 had conventional DCR. The functional success rate for VDCR was 83.3, 95 % confidence intervals (95%CI) [lower 0.68, upper 0.92] and for conventional DCR was 73.9 %, 95%CI [lower 0.54, upper 0.87]; without statistically significant difference (p = 0.38). VDCR patients rated higher aesthetic outcome on VAS (mean scores 95.5 ± 16.8 vs 82.9 ± 25.1, p = 0.03). On the SBSES, both observers gave higher aesthetic scores to the VDCR group (observer #1 4.6 ± 1.1 and #2 4.7 ± 1.2, p < 0.01) than conventional DCR (observer #1 3.1 ± 2.8 and #2 2.8 ± 2.1, p < 0.01). More patients reported that they could wear spectacles within 1 week post-VDCR (44.7 vs 4.3 %, p < 0.01). CONCLUSION: "V-incision" external DCR has a similar functional success rate to that of the conventional approach and has superior aesthetic outcomes as reported by surgeons and patients. However, a higher proportion of trainees under supervision performed conventional DCR, and it is uncertain whether the outcomes were also influenced by the level of surgeon's expertise.

FACTORS INFLUENCING NEED FOR RETREATMENT AND LONG-TERM VISUAL OUTCOME AFTER INTRAVITREAL BEVACIZUMAB FOR MYOPIC CHOROIDAL NEOVASCULARIZATION.

PURPOSE: To evaluate the efficacy and the predictive factors associated with the need for retreatment and long-term visual outcome after intravitreal bevacizumab for myopic choroidal neovascularization (CNV). METHODS: Retrospective cohort study of 93 eyes with subfoveal or juxtafoveal myopic CNV treated initially with either 3-monthly or single intravitreal bevacizumab injections followed by pro re nata retreatment. The efficacy was evaluated by the best-corrected visual acuity (BCVA) during follow-up visits. Backward stepwise multiple linear regression analyses were performed to evaluate the potential predictive factors on final BCVA, change in BCVA, and number of injections. Multiple logistic regression was performed to evaluate the potential predictive factors for retreatment. RESULTS: The mean follow-up duration was 25.12 ± 11.18 (SD) months. The mean logMAR BCVA at baseline was 0.72 ± 0.58 logMAR (20/100 Snellen equivalent) and was maintained at 0.39 ± 0.46 logMAR (20/50 Snellen equivalent) at the last follow-up (P < 0.001). The mean number of injections was 3.53 ± 1.70 (range, 3-10), and a total of 25 eyes (26.9%) received retreatment. Patients who received single loading injection had significantly lower mean total number of injections (1.50 ± 0.73 vs. 3.96 ± 1.53). Both subfoveal and juxtafoveal myopic CNV eyes had significant improvement in BCVA (0.28 ± 0.43 vs. 0.22 ± 0.32 [20/40 vs 20/30 Snellen equivalent], P = 0.506), and juxtafoveal myopic CNV eyes had significantly better BCVA at baseline and at the last follow-up than the subfoveal group. Treatment-naive eyes had significant improvement from baseline BCVA, and the amount of improvement was significantly more than those who received previous photodynamic therapy (0.31 ± 0.43 vs. 0.06 ± 0.11 [20/40 vs 20/25 Snellen equivalent], P < 0.001). Multivariate stepwise regression analysis showed that the baseline CNV size (P < 0.05), baseline BCVA (P < 0.001), and duration of symptoms (P < 0.05) were significant predictive factors for final BCVA, and BCVA improvement. Multiple logistic regression analysis identified that CNV size (P = 0.014) and follow-up duration (P = 0.017) were significant predictive factors for retreatment. No significant association was found for number of injections. CONCLUSION: Intravitreal bevacizumab seems to be an effective treatment for both subfoveal and juxtafoveal myopic CNV in the long term. Patients presented with shorter duration of symptoms and smaller CNV size before treatment as significant prognostic factors that predict better visual outcome. Eyes with longer follow-up duration and larger baseline CNV size may have higher risk for retreatment.

Angle-recession glaucoma: long-term clinical outcomes over a 10-year period in traumatic microhyphema.

This study aims to determine the incidence of angle recession and glaucoma after traumatic microhyphema. Records of all patients treated for traumatic hyphema or microhyphema admitted to a district hospital throughout a 10-year period were retrospectively reviewed. Patients with open-globe injury were excluded. The following clinical features were recorded during patients' initial presentation and follow-up visits: Snellen visual acuity, examination with slit-lamp biomicroscopy, intraocular pressure (IOP), dilated fundoscopic examination, gonioscopic examination and treatment. For patients with IOP > 21 mmHg and requiring glaucoma medications, visual field tests were performed. A total of 97 patients met the study criteria, of which 62 had microhyphema and 35 had gross hyphema. Among the traumatic microhyphema patients, 47 (75.8 %) had angle recession and 4 (6.5 %) had glaucoma with mean follow-up of 49 months (range 6-98 months). A statistically significant association was found between angle recession greater than 180° and the occurrence of glaucoma (p < 0.01). No statistically significant differences were found between groups of patients with microhyphema or gross hyphema regarding the incidence of angle recession and glaucoma. The complications of angle recession and glaucoma in patients after traumatic microhyphema appear similar to those found in patients after gross hyphema.

Amelioration of Functional, Metabolic, and Morphological Deterioration in the Retina following Retinal Detachment by Green Tea Extract.

Retinal detachment (RD) can result in the loss of photoreceptors that cause vision impairment and potential blindness. This study explores the protective effects of the oral administration of green tea extract (GTE) in a rat model of RD. Various doses of GTE or epigallocatechin gallate (EGCG), the most active ingredient in green tea catechins, were administered to Sprague Dawley (SD) rats with experimentally induced retinal detachment. The rats received sub-retinal injections of hyaluronic acid (0.1%) to induce RD and were given different doses of GTE and EGCG twice daily for three days. Notably, a low dose of GTE (142.9 mg/kg) caused significantly higher signal amplitudes in electroretinograms (ERGs) compared to higher GTE doses and any doses of EGCG. After administration of a low dose of GTE, the outer nuclear layer thickness, following normalization, of the detached retina reduced to 82.4 ± 8.2% (Mean ± SEM, p < 0.05) of the thickness by RD treatment. This thickness was similar to non-RD conditions, at 83.5 ± 4.7% (Mean ± SEM) of the thickness following RD treatment. In addition, the number of TUNEL-positive cells decreased from 76.7 ± 7.4 to 4.7 ± 1.02 (Mean ± SEM, p < 0.0001). This reduction was associated with the inhibition of apoptosis through decreased sphingomyelin levels and mitigation of oxidative stress shown by a lowered protein carbonyl level, which may involve suppression of HIF-1α pathways. Furthermore, GTE showed anti-inflammatory effects by reducing inflammatory cytokines and increasing resolving cytokines. In conclusion, low-dose GTE, but not EGCG, significantly alleviated RD-induced apoptosis, oxidative stress, inflammation, and energy insufficiency within a short period and without affecting energy metabolism. These findings suggest the potential of low-dose GTE as a protective agent for the retina in RD.

Improved accuracy of spectral-domain optical coherence tomography and optical coherence tomography angiography for monitoring myopic macular neovascularisation activity.

BACKGROUND/AIMS: To evaluate the diagnostic accuracy of spectral-domain optical coherence tomography (SD OCT) combined with OCT angiography (OCTA) for myopic myopic macular neovascularisation (MNV) activity. METHODS: Both eyes of patients with myopic MNV diagnosed with fluorescein angiography (FA), SD OCT and OCTA were assessed by unmasked investigators. The images were deidentified and randomised before graded by masked investigators, who determined the presence of active myopic MNV by using SD OCT together with OCTA without FA and by FA alone, respectively. The findings of masked investigators were compared with unmasked investigators. RESULTS: 213 eyes of 110 patients comprising 499 imaging episodes were eligible for grading. For diagnosing new-onset myopic MNV without FA, combined use of SD OCT and OCTA had a sensitivity of 0.94, specificity of 0.84 and area under the curve (AUC) of 0.92. FA had a sensitivity of 0.52 (p<0.01), specificity of 0.80 (p=0.38) and AUC of 0.66 (p<0.01). For recurrent myopic MNV, the combination of SD OCT and OCTA had a sensitivity of 0.98, specificity of 0.78 and AUC of 0.88. FA had a sensitivity of 0.50 (p=0.04), specificity of 0.76 (p=0.85) and AUC of 0.63 (p=0.01). Myopic traction maculopathy was more frequently associated with recurrent myopic MNV (p<0.01). CONCLUSION: SD OCT with dense volumetric scan was highly sensitive for diagnosing myopic MNV. The addition of OCTA improved the diagnostic specificity without FA. Monitoring of the longitudinal changes on SD OCT and judicious use of FA is a reliable surveillance strategy for myopic MNV.

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.

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.

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.

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.

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.

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.

Optical Coherence Tomography Angiography Compared with Multimodal Imaging for Diagnosing Neovascular Central Serous Chorioretinopathy.

PURPOSE: To assess the diagnostic accuracy of optical coherence tomography angiography (OCTA) compared with multimodal imaging for choroidal neovascularization (CNV) in central serous chorioretinopathy (CSC) eyes and to determine the features that predicted CNV. DESIGN: Prospective cross-sectional study. METHODS: Consecutive CSC patients were recruited from retina clinic. The reference standard for CNV was determined by interpretation of multimodal imaging with OCTA, structural OCT line scan, fluorescein angiography (FA), indocyanine green angiography (ICGA), ultra-widefield fundus photography and fundus autofluorescence (FAF). Two independent masked graders examined OCTA without FA and ICGA to diagnose CNV. Univariate and multivariate analyses were performed to evaluate factors associated with CNV. RESULTS: CNV was detected in 69 eyes in 64 out of 277 CSC patients according to reference standard. The two masked graders who examined OCTA had sensitivity of 81.2% (95% Confidence Interval [CI], 71.9%-90.4%) and 78.3% (95% CI, 68.5%-88.0%), specificity of 97.3% (95% CI, 95.9%-98.8%) and 96.2% (95% CI, 94.5%-98.0%), positive predictive values of 82.4% (95% CI, 73.3%-91.4%) and 76.1% (95% CI, 66.1%-86.0%), and negative predictive values of 97.1% (95% CI, 95.6%-98.7%) and 96.7% (95% CI, 95.0%-98.3%). Their mean area under the receiver operating characteristic curve (AUC) was 0.88 with good agreement (Kappa coefficient 0.80 [95% CI, 0.72-0.89]). Flat irregular pigment epithelial detachment on structural OCT, neovascular network on OCTA and ill-defined late leakage on FA significantly correlated with CNV in CSC from multiple regression (P < 0.001, P < 0.001 and P = 0.005, respectively). CONCLUSIONS: There is discordance between OCTA and multimodal imaging in diagnosing CNV in CSC. This study demonstrated the caveats in OCTA interpretation, such as small extrafoveal lesions and retinal pigment epithelial alterations. Comprehensive interpretation of OCTA with dye angiography and structural OCT is recommended.

Comorbidity of dementia and age-related macular degeneration calls for clinical awareness: a meta-analysis.

AIM: To determine the association between dementia and age-related macular degeneration (AMD) using meta-analysis. METHODS: We searched in the MEDLINE, EMBASE, Web of Knowledge, PsycInfo and Cochrane database of systematic reviews for studies published from March 1959 to March 2018. We included cross-sectional, case-control and cohort studies that evaluated the association of dementia/Alzheimer's disease (AD) with AMD (as outcome) and the association of AMD with dementia/AD (as outcome). Studies that compared cognitive functions between AMD and controls were also included. The summary outcomes, namely odds ratio (OR), relative risk, mean differences and corresponding 95% CIs, were estimated using random effects models. We performed sensitivity analysis based on study quality and individual study effect to control for potential biases. RESULTS: Among 2159 citation records, we identified 21 studies consisting of 7 876 499 study subjects for meta-analysis. Patients with dementia (padjusted≤0.017, OR≥1.24, I2≤9%) or AD (p=0.001, ORunadjusted=2.22, I2=50%) were at risk for AMD, particularly for late AMD (padjusted<0.001, OR=1.37, I2=0). AMD was also significantly associated with increased risk of AD/cognitive impairment (padjusted=0.037, OR=2.42, I2=38%). Moreover, patients with AMD had poorer cognitive functions when compared with controls, including Mini-Mental State Examination (p<0.001, I2≤79%) and Trail Making Test A (p<0.001, I2=0). Sensitivity analysis and Egger's test indicated our results were less likely biased. CONCLUSIONS: A significant association between dementia/AD and AMD calls for greater clinical awareness. The cost-effectiveness of routine screening for the other condition in patients with primary diagnosis of dementia/AD or AMD requires further study.

Impact of virtual reality simulation on learning barriers of phacoemulsification perceived by residents.

OBJECTIVE: To identify residents' perceived barriers to learning phacoemulsification surgical procedures and to evaluate whether virtual reality simulation training changed these perceptions. DESIGN: The ophthalmology residents undertook a simulation phacoemulsification course and proficiency assessment on the Eyesi system using the previously validated training modules of intracapsular navigation, anti-tremor, capsulorrhexis, and cracking/chopping. A cross-sectional, multicenter survey on the perceived difficulties in performing phacoemulsification tasks on patients, based on the validated International Council of Ophthalmology's Ophthalmology Surgical Competency Assessment Rubric (ICO-OSCAR), using a 5-point Likert scale (1 = least and 5 = most difficulty), was conducted among residents with or without prior simulation training. Mann-Whitney U tests were carried out to compare the mean scores, and multivariate regression analyses were performed to evaluate the association of lower scores with the following potential predictors: 1) higher level trainee, 2) can complete phacoemulsification most of the time (>90%) without supervisor's intervention, and 3) prior simulation training. SETTING: The study was conducted in ophthalmology residency training programs in five regional hospitals in Hong Kong. RESULTS: Of the 22 residents, 19 responded (86.3%), of which 13 (68.4%) had completed simulation training. Nucleus cracking/chopping was ranked highest in difficulty by all respondents followed by capsulorrhexis completion and nucleus rotation/manipulation. Respondents with prior simulation training had significantly lower difficulty scores on these three tasks (nucleus cracking/chopping 3.85 vs 4.75, P = 0.03; capsulorrhexis completion 3.31 vs 4.40, P = 0.02; and nucleus rotation/manipulation 3.00 vs 4.75, P = 0.01). In multivariate analyses, simulation training was significantly associated with lower difficulty scores on these three tasks. CONCLUSION: Residents who had completed Eyesi simulation training had higher confidence in performing the most difficult tasks perceived during phacoemulsification.