Genome-wide association studies identify two novel loci conferring susceptibility to diabetic retinopathy in Japanese patients with type 2 diabetes.

Several reports have suggested that genetic susceptibility contributes to the development and progression of diabetic retinopathy. We aimed to identify genetic loci that confer susceptibility to diabetic retinopathy in Japanese patients with type 2 diabetes. We analysed 5 790 508 single nucleotide polymorphisms (SNPs) in 8880 Japanese patients with type 2 diabetes, 4839 retinopathy cases and 4041 controls, as well as 2217 independent Japanese patients with type 2 diabetes, 693 retinopathy cases and 1524 controls. The results of these two genome-wide association studies (GWAS) were combined with an inverse variance meta-analysis (Stage-1), followed by de novo genotyping for the candidate SNP loci (P < 1.0 × 10-4) in an independent case-control study (Stage-2, 2260 cases and 723 controls). After combining the association data (Stages 1 and 2) using meta-analysis, the associations of two loci reached a genome-wide significance level: rs12630354 near STT3B on chromosome 3, P = 1.62 × 10-9, odds ratio (OR) = 1.17, 95% confidence interval (CI) 1.11-1.23, and rs140508424 within PALM2 on chromosome 9, P = 4.19 × 10-8, OR = 1.61, 95% CI 1.36-1.91. However, the association of these two loci was not replicated in Korean, European or African American populations. Gene-based analysis using Stage-1 GWAS data identified a gene-level association of EHD3 with susceptibility to diabetic retinopathy (P = 2.17 × 10-6). In conclusion, we identified two novel SNP loci, STT3B and PALM2, and a novel gene, EHD3, that confers susceptibility to diabetic retinopathy; however, further replication studies are required to validate these associations.

Sequential structural and functional change in geographic atrophy on multimodal imaging in non-exudative age-related macular degeneration.

PURPOSE: To investigate the temporal order of photoreceptor atrophy, retinal pigment epithelium (RPE) atrophy and visual acuity loss in patients with center-involving geographic atrophy (GA) in non-exudative age-related macular degeneration (neAMD). METHODS: Forty eyes of 25 consecutive patients who eventually developed center-involving GA were investigated. Fundus autofluorescence (FAF) and infrared image coupled optical coherence tomography (OCT) were acquired at each visit. Development of RPE atrophy and photoreceptor atrophy was defined as abnormal hyper/hypo-fluorescence on FAF and photoreceptor loss on OCT over 50% of the vertical or horizontal diameters of the center 1 mm circle, respectively. Visual acuity loss was defined as worsening of more than 0.2 logMAR compared to baseline. Kaplan-Meier analyses was performed to compare the sequential order of these three events. RESULTS: Mean age was 72.72 ± 8.63 years, and follow-up duration was 27.36 ± 17.22 months, with an average number of visits of 3.04 ± 1.54 during follow-up. GA progressed from photoreceptor atrophy on OCT, RPE atrophy on FAF, and then to vision loss (p < 0.001). The median survival time of photoreceptors preceded that of visual acuity by 16.3 months, and the median survival time of RPE preceded that of visual acuity by 7.0 months. At baseline, majority of eyes showed drusen only (57.5%), while the most common feature was incomplete RPE and outer retinal atrophy at 3-year follow-up (40.4%). CONCLUSION: In the progression of center-involving GA, photoreceptor atrophy on OCT and RPE atrophy on FAF precedes visual decline, and can act as biomarkers predicting future visual decline within the following years.

COVID-19 reduced scleral buckling training in fellows and shifted young ophthalmologists' preference toward vitrectomy: An Asia-Pacific survey.

BACKGROUND: To assess rhegmatogenous retinal detachment (RRD) surgery trends and training among young ophthalmologists (YOs, vitreoretinal fellows or attendings/consultants with ≤10 years of independent practice) and the impact of the COVID-19 pandemic. METHODS: An anonymous online survey was completed by 117 YOs in the Asia-Pacific regarding their RRD surgery experiences in 2021-2022. RESULTS: To achieve a 90% probability of surgical competency, 91 vitrectomy and 34 scleral buckling (SB) completions during fellowship were needed. In total, 49 (41.9%) YOs had fellowship affected by COVID-19. In the COVID versus pre-COVID era, however, the volume of SB completions per fellowship year decreased significantly (median [IQR] 3.3 [1.5, 9] vs. 13 [6.5, 23]; p < 0.001) and was lower than the required volume to achieve competency. YOs were less confident in conducting SB versus vitrectomy (3.5 ± 1.1 vs. 4.2 ± 0.8, p < 0.001), and they reported a decrease in the proportion of SB (-3.1%, p = 0.047) and an increase in the proportion of vitrectomy (+4.8%, p < 0.001) after the pandemic outbreak. Apart from RRD clinical characteristics, surgical confidence is among the main factors that affect surgical method decisions. During the pandemic, more YOs may have avoided SB due to the need for general anaesthesia, leading to longer surgical time and risk of viral transmission during intubation/extubation. CONCLUSIONS: SB surgical exposure is suboptimal in most fellowship programs in the 11 Asia-Pacific countries/regions we surveyed and further declined during the COVID-19 pandemic. YOs are less confident in performing SB, leading to a trend toward primary vitrectomy since the COVID-19 outbreak.

INFECTIOUS ENDOPHTHALMITIS AFTER SCLERAL FIXATION OF AN INTRAOCULAR LENS.

PURPOSE: To determine the mechanism of infection, clinical features, and risk factors of endophthalmitis after scleral fixation of an intraocular lens. METHODS: We included 15 patients with infectious endophthalmitis after scleral fixation of an intraocular lens between April 2004 and December 2017, as well as four patients found through a literature search. Thus, a total of 19 patients were analyzed. RESULTS: Among 19 eyes, infectious endophthalmitis developed at a mean of 23 months (range: 1 day-10 years) after scleral fixation surgery. Nine eyes (47.4%) had early-onset endophthalmitis (≤6 weeks), and 10 eyes (52.6%) had delayed-onset endophthalmitis (>6 weeks). Eleven eyes (57.9%) had presumed microbial influx due to suture exposure. Those with delayed-onset endophthalmitis showed a higher rate of suture-related infection (80.0% vs. 33.3%) and culture of gram-negative bacteria (70.0% vs. 12.5%) than did those with early-onset endophthalmitis. CONCLUSIONS: Infectious endophthalmitis can develop late after scleral fixation of an intraocular lens, usually related to the exposed sutures, and the visual prognosis is poor. Eyes that have sutured scleral fixation should be monitored regularly, and preventive measures should be performed if an exposed suture is found.

CFH and VIPR2 as susceptibility loci in choroidal thickness and pachychoroid disease central serous chorioretinopathy.

Central serous chorioretinopathy (CSC) is a common disease affecting younger people and may lead to vision loss. CSC shares phenotypic overlap with age-related macular degeneration (AMD). As recent studies have revealed a characteristic increase of choroidal thickness in CSC, we conducted a genome-wide association study on choroidal thickness in 3,418 individuals followed by TaqMan assays in 2,692 subjects, and we identified two susceptibility loci: CFH rs800292, an established AMD susceptibility polymorphism, and VIPR2 rs3793217 (P = 2.05 × 10-10 and 6.75 × 10-8, respectively). Case-control studies using patients with CSC confirmed associations between both polymorphisms and CSC (P = 5.27 × 10-5 and 5.14 × 10-5, respectively). The CFH rs800292 G allele is reportedly a risk allele for AMD, whereas the A allele conferred risk for thicker choroid and CSC development. This study not only shows that susceptibility genes for CSC could be discovered using choroidal thickness as a defining variable but also, deepens the understanding of differences between CSC and AMD pathophysiology.

Retina thickness as a marker of neurodegeneration in prodromal lewy body disease.

OBJECTIVES: We investigated retinal change and its relationship with neurodegeneration markers in a prodromal Parkinson cohort. METHODS: A total of 30 patients with idiopathic rapid eye movement sleep behavior disorder were recruited. Participants underwent olfactory testing, macular optical coherence tomography, microperimetry, contrast sensitivity test, and brain N-(3-[18 F]fluoropropyl)-2-carbomethoxy-3-(4-iodophenyl) nortropane positron emission tomography. We measured the ganglion cell complex thicknesses and investigated its correlation with olfactory function and striatal dopamine transporter availability. A linear mixed-effect model was applied with adjustment for multiple comparisons. RESULTS: The parafoveal ganglion-cell-complex thickness in this cohort lay between our healthy control and drug-naïve Parkinson's disease group data. Idiopathic rapid eye movement sleep behavior disorder patients also had contrast sensitivity impairment as in Parkinson's disease with a nonsignificant change in macular sensitivities. Macular ganglion cell complex thickness correlated with olfactory scores and with striatal dopamine transporter availabilities. CONCLUSIONS: Macular ganglion cell complex thinning may be a marker of neurodegeneration in prodromal Parkinson's disease. © 2019 International Parkinson and Movement Disorder Society.

Contrast sensitivity impairment in drug-naïve Parkinson's disease patients associates with early cognitive decline.

OBJECTIVES: To investigate the contrast sensitivity function in drug-naïve Parkinson's disease (PD) patients and its predictive value with longitudinal follow-up data. METHODS: We included newly diagnosed non-demented PD patients who performed contrast sensitivity test between 2013 and 2014. Contrast sensitivity function at drug-naïve state in PD patients was compared with age-matched normal control data of our center. Correlation between contrast sensitivity function and parkinsonian motor and non-motor features including the Mini-Mental State Exam (MMSE) score at the time of diagnosis were analyzed by linear regression. With longitudinal follow-up data after initiating anti-parkinsonian therapy, the risk conferred on subsequent visual hallucinations and cognitive impairment requiring anti-dementia drugs was analyzed by dichotomizing PD group based on the initial contrast sensitivity function. RESULTS: Forty-eight patients were finally included, and mean follow-up periods were 43 months. Contrast sensitivity function in drug-naïve PD patients was significantly worse than controls. Contrast sensitivity function correlated with sleep disturbance (p = 0.001) and global cognitive status reflected by the MMSE score (p = 0.020). It also associated with further decline in the MMSE during the follow-ups (p = 0.029). Patients with below average contrast sensitivity function at the time of diagnosis showed higher risk of cognitive decline requiring anti-dementia drugs (adjusted odds ratio = 4.68, p = 0.04) and of visual hallucinations (adjusted odds ratio = 12.54, p = 0.04) than those above average function during the follow-up. CONCLUSION: Contrast sensitivity impairment in drug-naïve PD patients associates with clinical demand for therapeutic intervention of cognitive decline as well as development of visual hallucinations in the early course of the disease.

Macular ganglion-cell-complex layer thinning and optic nerve integrity in drug-naïve Parkinson's disease.

To reveal the macular inner retinal change linked to axonal degeneration in Parkinson's disease (PD), we performed macular optical coherence tomography scan and diffusion tensor imaging of the retrobulbar optic nerve on both eyes of 36 drug-naïve PD patients. Thicknesses of inner retinal layers were automatically measured, and correlation analysis was conducted between the retinal thickness and diffusion parameters of the optic nerve. PD patients showed thinning of the inner retinal layers compared to control data. Thicknesses of the ganglion cell and inner plexiform layers were both correlated positively with fractional anisotropy and negatively with diffusivity indices of ipsilateral optic nerve (FDR-adjusted p < 0.05). This study revealed a novel in vivo connection between macular parafoveal ganglion cell change and integrity in the retrobulbar optic nerve in drug-naïve PD.

Shared genetic variants for polypoidal choroidal vasculopathy and typical neovascular age-related macular degeneration in East Asians.

Polypoidal choroidal vasculopathy (PCV), a subtype of age-related macular degeneration (AMD) more frequently seen in East Asians, has both common and distinct clinical manifestations with typical neovascular AMD (tAMD). We aim to examine the extent to which common genetic variants are shared between these two subtypes. We performed the meta-analysis of association in a total of 1062 PCV patients, 1157 tAMD patients and 5275 controls of East Asian descent from the Genetics of AMD in Asians Consortium at the 34 known AMD loci. A total of eight loci were significantly associated with PCV, including age-related maculopathy susceptibility 2 (ARMS2)-HtrA serine peptidase 1 (HTRA1), complement factor H (CFH), C2-CFB-SKIV2L, CETP, VEGFA, ADAMTS9-AS2 and TGFBR1 (P<5 × 10-4) from the single-nucleotide polymorphism-based test and COL4A3 from the gene-based tests (Pgene=2.02 × 10-4). PCV and tAMD are genetically highly correlated (rg=0.69, P=4.68 × 10-3), with AMD known loci accounting for up to 36% variation. Weaker association for PCV was observed at ARMS2-HTRA1 (Pdif=4.39 × 10-4) and KMT2E-SRPK2(Pdif=4.43 × 10-3), compared with tAMD. Variants at CFH, CETP and VEGFA exhibited different association signals in East Asians, in contrast to those in European individuals. Our data suggest a substantially shared genetic susceptibility for PCV and tAMD, while also highlight the unique associations for PCV, which is useful in understanding the pathogenesis of PCV.

Age-related macular degeneration: prevalence and risk factors from Korean National Health and Nutrition Examination Survey, 2008 through 2011.

OBJECTIVE: To investigate the prevalence and risk factors of age-related macular degeneration (AMD) in the Korean population. DESIGN: A cross-sectional study using a complex, stratified, multistage, probability-cluster survey, which can produce nationally representative estimates. PARTICIPANTS: Using the database of Korean National Health and Nutrition Examination Survey from 2008 through 2011, 14 352 participants 40 years of age or older with gradable fundus photographs were included. METHODS: Age-related macular degeneration was determined by fundus photograph. Prevalences of AMDs were estimated. Risk factor analyses were conducted using logistic regression analyses (LRAs). MAIN OUTCOME MEASURES: Prevalence and risk factors of AMD. RESULTS: The prevalence of AMD was 6.62% (95% confidence interval [CI], 6.15%-7.09%) in the Korean population: 6.02% (95% CI, 5.56%-6.48%) were early AMD and 0.60% (95% CI, 0.45%-0.75%) were late AMD. The prevalence of early AMD in women (6.73%; 95% CI, 6.11%-7.35%) was higher than that in men (5.25%; 95% CI, 4.61%-5.89%; P<0.001), and the prevalence of late AMD in women (0.37%; 95% CI, 0.22%-0.52%) was lower than that in men (0.85%; 95% CI, 0.59%-1.12%; P<0.001). However, in multiple LRAs both early and late AMD had no association with gender, house income, residence, sun exposure, or systemic comorbidities, including hypertension, diabetes mellitus, and cardiovascular diseases. Early AMD had positive associations with older age groups (P<0.001), lower education (P = 0.027), occupation (P<0.001), anemia (P = 0.027), hepatitis B surface antigen carrier status (P<0.001), not being overweight (body mass index [BMI], P = 0.032; waist circumference, P = 0.041, in separate analyses), and higher serum high-density lipoprotein (HDL) level (P = 0.046), but not with smoking status. Late AMD had positive associations with age groups (P<0.001), current smokers (P = 0.022), and lower BMI (P = 0.037). CONCLUSIONS: The results suggest that there are 1.21 million individuals with early AMD and 121 000 individuals with late AMD in Korea. Nonoverweight status and higher HDL levels, generally assumed as positive health indicators, as well as anemia and hepatitis B infection had harmful associations with AMD in our study, implying a possible different pathophysiologic process of AMD in Asians compared with that of white persons.

Retinal nerve fiber layer thickness and visual hallucinations in Parkinson's Disease.

Defective visual information processing from both central and peripheral pathways is one of the suggested mechanisms of visual hallucination in Parkinson's disease (PD). To investigate the role of retinal thinning for visual hallucination in PD, we conducted a case-control study using spectral domain optical coherence tomography. We examined a representative sample of 61 patients with PD and 30 healthy controls who had no history of ophthalmic diseases. General ophthalmologic examinations and optical coherence tomography scans were performed in each participant. Total macular thickness and the thickness of each retinal layer on horizontal scans through the fovea were compared between the groups. In a comparison between patients with PD and healthy controls, there was significant parafoveal inner nuclear layer thinning, whereas other retinal layers, including the retinal nerve fiber layer, as well as total macular thicknesses were not different. In terms of visual hallucinations among the PD subgroups, only retinal nerve fiber layer thickness differed significantly, whereas total macular thickness and the thickness of other retinal layers did not differ. The retinal nerve fiber layer was thinnest in the group that had hallucinations without dementia, followed by the group that had hallucinations with dementia, and the group that had no hallucinations and no dementia. General ophthalmologic examinations did not reveal any significant correlation with hallucinations. There were no significant correlations between retinal thicknesses and duration or severity of PD and medication dosages. The results indicate that retinal nerve fiber layer thinning may be related to visual hallucination in nondemented patients with PD. Replication studies as well as further studies to elucidate the mechanism of thinning are warranted.

Photoreceptor change and visual outcome after idiopathic epiretinal membrane removal with or without additional internal limiting membrane peeling.

PURPOSE: To compare the postoperative photoreceptor status and visual outcome after epiretinal membrane removal with or without additional internal limiting membrane (ILM) peeling. METHODS: Medical records of 40 eyes from 37 patients undergoing epiretinal membrane removal with residual ILM peeling (additional ILM peeling group) and 69 eyes from 65 patients undergoing epiretinal membrane removal without additional ILM peeling (no additional peeling group) were reviewed. The length of defects in cone outer segment tips, inner segment/outer segment junction, and external limiting membrane line were measured using spectral domain optical coherence tomography images of the fovea before and at 1, 3, 6, and 12 months after the surgery. RESULTS: Cone outer segment tips and inner segment/outer segment junction line defects were most severe at postoperative 1 month and gradually restored at 12 months postoperatively. The cone outer segment tips line defect in the additional ILM peeling group was significantly greater than that in the no additional peeling group at postoperative 1 month (P = 0.006), and best-corrected visual acuity was significantly worse in the former group at the same month (P = 0.001). There was no significant difference in the defect size and best-corrected visual acuity at subsequent visits and recurrence rates between the two groups. CONCLUSION: Patients who received epiretinal membrane surgery without additional ILM peeling showed better visual and anatomical outcome than those with additional ILM peeling at postoperative 1 month. However, surgical outcomes were comparable between the two groups, thereafter. In terms of visual outcome and photoreceptor integrity, additional ILM peeling may not be an essential procedure.

Associated factors and treatment outcome of presumed noninfectious endophthalmitis occurring after intravitreal triamcinolone acetonide injection.

BACKGROUND: To investigate the associated factors and treatment outcomes in patients with presumed noninfectious endophthalmitis after intravitreal triamcinolone acetonide (IVTA) injection. METHODS: Among 219 consecutive cases of 186 patients who had undergone IVTA injection for macular diseases, presumed noninfectious endophthalmitis was diagnosed if the patient showed severe inflammation in the anterior chamber and vitreous cavity within 7 days after injection but no organism was isolated on microbiological examination. Clinical features and previously performed surgical procedures were evaluated to assess their association with presumed noninfectious endophthalmitis using logistic regression. After surgical or medical treatment for endophthalmitis, the visual outcome was evaluated in all patients. RESULTS: Noninfectious endophthalmitis developed in six of 219 eyes (2.7 %). Previous vitrectomy, history of IVTA injection, and pseudophakia were significantly associated with the occurrence of presumed noninfectious endophthalmitis after IVTA injection (p = 0.049, 0.034, and 0.009, respectively). Internal limiting membrane (ILM) peeling during vitrectomy also showed statistically significant association (odds ratio = 13.6, p = 0.017). Five of six patients (83.3 %) regained pre-injection vision. CONCLUSION: In addition to previous vitrectomy, history of IVTA injection, internal limiting membrane (ILM) peeling, and pseudophakia may render the eye vulnerable to presumed noninfectious endophthalmitis following IVTA injection. Visual outcome shows generally good prognosis after treatment.

Comparison of Optical Coherence Tomography Biomarkers between Bevacizumab Good Responders and Nonresponders Who were Switched to Dexamethasone Implant in Diabetic Macular Edema.

PURPOSE: To compare volumetric optical coherence tomography (OCT) biomarkers in bevacizumab responsive and bevacizumab refractory diabetic macular edema (DME) patients switched to the dexamethasone implant to ultimately identify possible prognostic indicators. METHODS: Retrospective analysis of DME patients treated with bevacizumab were done. Patients were divided into those who showed response to bevacizumab (bevacizumab only group) and others who were switched to the dexamethasone implant due to lack of response to bevacizumab (switching group). Volumetric OCT biomarkers such as central macular thickness (CMT), inner and outer cystoid macular edema (CME) volume, serous retinal detachment (SRD) volume, retinal volume (CME + SRD volume) within the 6-mm Early Treatment of Diabetic Retinopathy Study circle were calculated. OCT biomarkers were followed up throughout treatment. RESULTS: Among total of 144 eyes, 113 patients were included in the bevacizumab only group and 31 patients were included in the switching group. Compared to the bevacizumab only group, the switching group showed higher baseline CMT (558.00 ± 209.60 µm vs. 454.96 ± 125.88 µm, p = 0.003), larger inner CME (6.02 ± 1.43 mm3 vs. 5.12 ± 0.87 mm3, p = 0.004) and SRD volume (0.32 ± 0.40 mm3 vs. 0.11 ± 0.09 mm3, p = 0.015) and higher proportion of patients with SRD (58.06% vs. 31.86%, p = 0.008). In the switching group, CMT, inner CME and SRD volume all showed significant reduction after switching to the dexamethasone implant. CONCLUSIONS: DME with large SRD and inner nuclear layer edema volume may be more effectively treated with the dexamethasone implant than bevacizumab.

Assessment of Risk Factors Affecting Refractive Outcomes after Phacovitrectomy for Epiretinal Membrane.

PURPOSE: To investigate factors associated with refractive outcomes after phacovitrectomy for epiretinal membrane (ERM). METHODS: Retrospective review of patients undergoing phacovitrectomy for ERM was done. The main outcome measure was predictive refraction error (PE), defined as observed refraction error - target refraction error, calculated by the SRK/T, Haigis, and SRK II formulae. PE was measured at postoperative 1, 3, and 6 months. Simple and multiple linear regression analysis were used to evaluate factors associated with PE. RESULTS: A total of 53 eyes of 53 patients were included. The mean PEs at postoperative 1, 3, and 6 months were all negative, implying myopic shift in all patients regardless of the intraocular lens formula used. Haigis formula showed the least myopic shift among the three formulae (p = 0.001, Friedman test). There was no significant difference in PE depending on preoperative central macular thickness (CMT) in subgroup analysis. On stepwise multiple linear regression analysis, ERM etiology (ß = 0.759, p = 0.004, SRK/T formula; ß = 0.733, p = 0.008, Haigis formula; ß = 0.933, p < 0.001, SRK II formula), preoperative anterior chamber depth (ß = -0.662, p = 0.013, Haigis formula; ß = -0.747, p = 0.003, SRK II formula), and decrease of CMT (ß = -0.003, p = 0.025, SRK/T formula) were significantly associated with PE at postoperative 6 months. CONCLUSIONS: Myopic shift in PE was observed after combined phacovitrectomy for epiretinal membrane. ERM etiology, preoperative anterior chamber depth, and decrease of CMT were significantly associated with PE at postoperative 6 months. There was no difference in PE after surgery between the two groups defined by CMT (≥500 and <500 µm).

Retina-to-brain spreading of α-synuclein after intravitreal injection of preformed fibrils.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the aggregation of misfolded α-synuclein and progressive spreading of the aggregates from a few discrete regions to wider brain regions. Although PD has been classically considered a movement disorder, a large body of clinical evidence has revealed the progressive occurrence of non-motor symptoms. Patients present visual symptoms in the initial stages of the disease, and accumulation of phospho-α-synuclein, dopaminergic neuronal loss, and retinal thinning has been observed in the retinas of PD patients. Based on such human data, we hypothesized that α-synuclein aggregation can initiate in the retina and spread to the brain through the visual pathway. Here, we demonstrate accumulation of α-synuclein in the retinas and brains of naive mice after intravitreal injection of α-synuclein preformed fibrils (PFFs). Histological analyses showed deposition of phospho-α-synuclein inclusions within the retina 2 months after injection, with increased oxidative stress leading to loss of retinal ganglion cells and dopaminergic dysfunction. In addition, we found accumulation of phospho-α-synuclein in cortical areas with accompanying neuroinflammation after 5 months. Collectively, our findings suggest that retinal synucleinopathy lesions initiated by intravitreal injection of α-synuclein PFFs spread to various brain regions through the visual pathway in mice.

Contribution of common and rare variants to Asian neovascular age-related macular degeneration subtypes.

Neovascular age-related macular degeneration (nAMD), along with its clinical subtype known as polypoidal choroidal vasculopathy (PCV), are among the leading causes of vision loss in elderly Asians. In a genome-wide association study (GWAS) comprising 3,128 nAMD (1,555 PCV and 1,573 typical nAMD), and 5,493 controls of East Asian ancestry, we identify twelve loci, of which four are novel ([Formula: see text]). Substantial genetic sharing between PCV and typical nAMD is noted (rg = 0.666), whereas collagen extracellular matrix and fibrosis-related pathways are more pronounced for PCV. Whole-exome sequencing in 259 PCV patients revealed functional rare variants burden in collagen type I alpha 1 chain gene (COL1A1; [Formula: see text]) and potential enrichment of functional rare mutations at AMD-associated loci. At the GATA binding protein 5 (GATA5) locus, the most significant GWAS novel loci, the expressions of genes including laminin subunit alpha 5 (Lama5), mitochondrial ribosome associated GTPase 2 (Mtg2), and collagen type IX alpha 3 chain (Col9A3), are significantly induced during retinal angiogenesis and subretinal fibrosis in murine models. Furthermore, retinoic acid increased the expression of LAMA5 and MTG2 in vitro. Taken together, our data provide insights into the genetic basis of AMD pathogenesis in the Asian population.

2023 Clinical Practice Guidelines for Diabetes Mellitus of the Korean Diabetes Association.

In May 2023, the Committee of Clinical Practice Guidelines of the Korean Diabetes Association published the revised clinical practice guidelines for Korean adults with diabetes and prediabetes. We incorporated the latest clinical research findings through a comprehensive systematic literature review and applied them in a manner suitable for the Korean population. These guidelines are designed for all healthcare providers nationwide, including physicians, diabetes experts, and certified diabetes educators who manage patients with diabetes or individuals at risk of developing diabetes. Based on recent changes in international guidelines and the results of a Korean epidemiological study, the recommended age for diabetes screening has been lowered. In collaboration with the relevant Korean medical societies, recently revised guidelines for managing hypertension and dyslipidemia in patients with diabetes have been incorporated into this guideline. An abridgment containing practical information on patient education and systematic management in the clinic was published separately.

Proteomic analysis of the aqueous humor in age-related macular degeneration (AMD) patients.

Age-related macular degeneration (AMD) can lead to irreversible central vision loss in the elderly. Although large number of growth factor pathways, including the vascular endothelial growth factor (VEGF), has been implicated in the pathogenesis of AMD, no study has directly assessed the whole proteomic composition in the aqueous humor (AH) among AMD patients. The AH contains proteins secreted from the anterior segment tissue, and these proteins may play an important role in the pathogenesis of AMD. Thus, comparisons between the AH proteomic profiles of AMD patients and non-AMD controls may lead to the verification of novel pathogenic proteins useful as potential clinical biomarkers. In this study, we used discovery-based proteomics and Multiple Reaction Monitoring Mass Spectrometry (MRM-MS) to analyze AH from AMD patients and AH from controls who underwent cataract surgery. A total of 154 proteins with at least two unique peptides were identified in the AH. Of these 154 proteins identified by discovery-based proteomics, 10 AH proteins were novel identifications. The protein composition in the AH was different between AMD patients and non-AMD controls. Subsequently, a systematic MRM-MS assay was performed in seven highly abundant differentially expressed proteins from these groups. Differential expression of three proteins was observed in the AH of AMD patients compared with that of cataract controls (p<0.0312). Elucidation of the aqueous proteome will establish a foundation for protein function analysis and identify differentially expressed markers associated with AMD. This study demonstrates that integrated proteomic technologies can yield novel biomarkers to detect exudative AMD.