Talaromides A-C, Bioactive Cyclic Heptapeptides from Talaromyces siglerae Isolated from a Marine Sponge.

Three new cyclic heptapeptides, talaromides A-C (1-3), were isolated from cultures produced by the fungus Talaromyces siglerae (Ascomycota), isolated from an unidentified sponge. The structures, featuring an unusual proline-anthranilic moiety, were elucidated by analysis of spectroscopic data and chemical transformations, including the advanced Marfey's method and GITC derivatization. Talaromides A and B inhibited migration activity against PANC-1 human pancreatic cancer cells without significant cytotoxicity.

Cavomycins A-C, Linear Oligomer Depsipeptides from an Annelid-Associated Streptomyces cavourensis.

Three unique linear oligomeric depsipeptides, designated as cavomycins A-C (1-3), were identified from Streptomyces cavourensis, a gut bacterium associated with the annelid Paraleonnates uschakovi. The structures of these depsipeptides were determined through a combination of spectroscopic methods and chemical derivatization techniques, including methanolysis, the modified Mosher's method, advanced Marfey's methods, and phenylglycine methyl ester derivatization. The unique dipeptidyl residue arrangements in compounds 1-3 indicate that they are not degradation products of valinomycin. Compound 2 and its methylation derivative 2a exhibited antiproliferative activity against PANC-1 pancreatic cancer cells with IC50 values of 1.2 and 1.7 µM, respectively.

MORPHOLOGICAL BIOMARKERS PREDICTING EXUDATIVE CONVERSION IN TYPE 1 NONEXUDATIVE MACULAR NEOVASCULARIZATION USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To investigate the incidence and morphological biomarkers to predict the exudative conversion in eyes with type 1 nonexudative macular neovascularization using swept-source optical coherence tomography angiography. METHODS: Macular neovascularizations were detected using the retinal pigment epithelium-to-retinal pigment epithelium-fit slab of swept-source optical coherence tomography angiography scan. Depending on whether exudation developed within a year, the eyes were divided into two groups: active and silent. Qualitative and quantitative optical coherence tomography angiography parameters of the two groups were evaluated to discriminate the biomarkers associated with exudative conversion. RESULTS: Of the 40 eyes, nine developed exudation within 1 year (incidence rate 22.5%). The active group exhibited a significantly higher "anastomosis and loops" pattern, greater "vessel density," increased "junction density," fewer "number of end points," and lower "lacunarity" compared with the silent group. "Anastomosis and loops" and higher "vessel density" were correlated with the active group in multivariate analyses. A predictive model combining these biomarkers achieved 95% accuracy in predicting exudative conversion. CONCLUSION: At 12 months, the risk of exudation was 22.5%, and "anastomosis and loops" and "vessel density" were useful optical coherence tomography angiography biomarkers for predicting exudative conversion in eyes with type 1 nonexudative macular neovascularization. For eyes with a high risk of exudative conversion, more frequent follow-up is recommended.

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.

Bioactive Piperazic Acid-Bearing Cyclodepsipeptides, Lydiamycins E-H, from an Endophytic Streptomyces sp. Associated with Cinnamomum cassia.

A chemical investigation of the endophytic Streptomyces sp. HBQ95, associated with the medicinal plant Cinnamomum cassia Presl, enabled the discovery of four new piperazic acid-bearing cyclodepsipeptides, lydiamycins E-H (1-4), and one known compound (lydiamycin A). Their chemical structures, including absolute configurations, were defined by a combination of spectroscopic analyses and multiple chemical manipulations. Lydiamycins F-H (2-4) and A (5) exhibited antimetastatic activity against PANC-1 human pancreatic cancer cells without significant cytotoxicity.

A 12-year nationwide cohort study on the association between central retinal artery occlusion and cancer.

PURPOSE: This study aims to investigate the association between incident central retinal artery occlusion (CRAO) and the subsequent development of cancer. METHODS: We included incident CRAO patients from the 2002-2013 National Health Insurance Service database in South Korea. For the patient cohort, we included patients diagnosed with CRAO from the database, and excluded patients having CRAO or any cancer history during the first 2-year washout period (2002-2003). Then, we defined their 1:4 propensity-score matched non-CRAO subjects as controls, all of whom also had no history of cancer during the washout period. Time-varying covariate Cox regression models were conducted to determine the association of CRAO with cancer. Kaplan-Meier curves with log-rank test were also analyzed. RESULTS: A total of 9712 patients with CRAO and 38,848 controls were included in the study. CRAO was associated with an increased risk of subsequent cancer (hazard ratio = 1.27; 95% confidence interval, 1.19-1.35). The incidence rate of overall cancer during the study period was 29.12 per 1000 person-years in the CRAO group and 22.77 per 1000 person-years in the control group. Incidence probability of overall cancer was significantly higher among CRAO patients than controls (P < 0.001, log-rank test). CONCLUSION: The risk of cancer occurrence was increased in patients with CRAO. The results supported that CRAO could be attributed to one of the consequences of arterial thrombosis in cancer patients.

THREE-DIMENSIONAL HEADS-UP VITRECTOMY VERSUS CONVENTIONAL MICROSCOPIC VITRECTOMY FOR PATIENTS WITH EPIRETINAL MEMBRANE.

PURPOSE: To investigate the efficacy and safety of 3D heads-up display (3D-HUD) vitrectomy compared with conventional microscopy (CM) vitrectomy in epiretinal membrane (ERM) surgery. METHODS: Epiretinal membrane removal with or without internal limiting membrane (ILM) peeling was performed using a 3D-HUD or CM system. The mean changes in best-corrected visual acuity (BCVA) and in central macular thickness (CMT) and postoperative complications were assessed. RESULTS: Baseline demographics were comparable except for the follow-up period. Both BCVA and CMT improved at the final visit (all P < 0.05). The ERM recurrence and dissociated optic nerve fiber layer (DONFL) rates were lower in the 3D group (both P < 0.05). conventional microscopic vitrectomy (odds ratio [OR] = 12.86, P = 0.02) and absence of ILM peeling (OR = 45.25, P < 0.05) were associated with ERM recurrence. In the DONFL, CM vitrectomy (OR = 1.98, <0.05) and combined phacovitrectomy (OR = 2.33, P = 0.03) were analyzed as risk factors for DONFL. CONCLUSION: The improvement in BCVA and CMT in ERM surgery using a 3D-HUD is comparable with that of CM vitrectomy, with a significantly low rate of ERM recurrence and DONFL occurrence. Therefore, 3D vitrectomy might have an advantage for ERM surgery.

Visual prognosis and surgical timing of Ahmed glaucoma valve implantation for neovascular glaucoma secondary to diabetic vitrectomy.

BACKGROUND: Evaluate the visual outcomes of Ahmed glaucoma valve implantation (AGVI) in patients with neovascular glaucoma (NVG) who underwent diabetic vitrectomy and suggest appropriate AGVI timing. METHODS: Medical records of patients who underwent AGVI due to NVG after diabetic vitrectomy were reviewed. Successful intraocular pressure (IOP) control was defined as an IOP between 6 and 21 mmHg. Visual outcome was compared before NVG diagnosis and after AGVI, and the "favorable" visual outcome was defined as a postoperative deterioration in BCVA of less than 0.3 logMAR units compared to those before the development of NVG. Various factors including surgical timing were evaluated to identify the risk factors associated with unfavorable visual outcome. RESULTS: A total of 35 eyes were enrolled and divided into group 1(medically uncontrolled NVG group, IOP more than 30mmHg, 16 eyes) and group 2(NVG group responded well to the initial non-surgical treatment but eventually required AGVI, 19 eyes). Despite the favorable rate of normalization of post-AGVI IOP (85.7%), 43.8% in Group 1 and 26.3% in Group 2 showed unfavorable visual outcomes. In group 1, delayed surgical timing more than 1 week from the NVG diagnosis showed a significant association with unfavorable visual outcomes (P = 0.041). In group 2, poor patient compliance (follow up loss, refuse surgery) was the main factor of unfavorable visual outcomes. CONCLUSION: When NVG occurs in patients with proliferative diabetic retinopathy after vitrectomy, physicians should be cautious not to delay the surgical intervention, especially in patients with IOP of 30 or more despite non-surgical treatment. Early AGVI within six days might be necessary to preserve useful vision in these patients.

Influence of Surgical Experience and Risk Factors for Surgical Failure in Primary Retinal Detachment Surgery.

INTRODUCTION: The aim of this study was to report surgical outcomes and risk factors for primary surgical failure following rhegmatogenous retinal detachment (RRD) repair. METHODS: In this retrospective cohort study, RRD patients who underwent primary surgery at a tertiary center between January 1, 2006, and December 31, 2020, were enrolled. Surgical failure was defined as reoperation within 60 days postoperatively due to retinal re-detachment and putative risk factors for surgical failure were analyzed. RESULTS: Of 2,383 eyes (2,335 patients), 1,342 (56.3%) underwent vitrectomy and 1,041 (43.7%) underwent scleral buckling. The surgical failure rate was 9.1% overall, and 6.0% and 13.1% for the vitrectomy and scleral buckling groups, respectively. In the multivariate logistic regression analysis, surgical failure was associated with surgical experience (first-year fellow vs. senior professor) (odds ratio [OR]: 1.66; p = 0.018), scleral buckling (OR: 2.33; p < 0.001), and longer axial length (AL; ≥26.5 mm) (OR: 1.49; p = 0.017). In each surgical approach, age <40 years (OR: 2.11; p = 0.029) in the vitrectomy group and age >40 years (OR, 1.84; p = 0.004), male sex (OR: 1.65; p = 0.015), and first-year fellows compared to senior professors (OR: 1.95; p = 0.013) in the scleral buckling group were associated with surgical failure. Lens status were not associated with the surgical failure rate. CONCLUSION: In this large retrospective study using data from Korea, vitrectomy was superior to scleral buckling in terms of primary anatomical outcomes in the management of RRD. First-year fellows were a risk factor for surgical failure, especially for scleral buckling. Longer AL was a significant parameter for predicting the success rates.

Short-Term Safety and Efficacy of Intravitreal Brolucizumab Injections for Neovascular Age-Related Macular Degeneration: A Multicenter Retrospective Real-World Study.

INTRODUCTION: The aim of the study was to determine the short-term real-world safety and efficacy of intravitreal brolucizumab injections in Korean patients with neovascular age-related macular degeneration (nAMD). METHODS: This multicenter retrospective study involved 294 eyes (treatment naïve 20 eye [6.8%] and nontreatment naïve 274 eyes [93.2%]) of 290 patients from 13 hospitals or retinal centers in South Korea. Patients with nAMD who received brolucizumab injection(s) between April 1 and November 30, 2021, with a follow-up ≥1 month, were included. Primary outcomes were safety, incidence of intraocular inflammation (IOI), and potential risk factors. The secondary outcome was efficacy, i.e., change in best-corrected visual acuity (BCVA) and optical coherence tomography-measured macular thickness and retinal fluid. RESULTS: The mean age was 71.63 ± 8.66. The follow-up period was 2.38 ± 0.79 months. The mean number of brolucizumab injections during the follow-up was 1.52 ± 0.58. The overall incidence of IOI was 13.9% (n = 41 eyes). Most IOI cases were of anterior uveitis (8.8%, 26 eyes), followed by retinal vasculitis (2.4%, seven eyes) and occlusive retinal vasculitis (0.3%, one eye). Most eyes showed IOI resolution (n = 40, 97.5%) and BCVA restoration (n = 39, 95.1%) with or without corticosteroid treatment during the follow-up. Age, sex, IOI history, or other anti-vascular endothelial growth factor injection histories were not associated with the occurrence of IOI. However, only thin subfoveal choroidal thickness (SFCT) was associated with the occurrence of IOI (odds ratio = 0.995, p = 0.020). BCVA at 1 month improved from baseline (baseline 0.518 ± 0.356 vs. 1 month 0.503 ± 0.383, p = 0.023), but the improvement was not maintained. Anatomical improvement was significant after 3 months. CONCLUSION: In Korean patients with nAMD, the incidence of IOI following brolucizumab injections was 13.9%. IOI was well-controlled with or without steroid treatment. Most IOI eyes (95.1%) were restored to the level of vision before. IOI occurrence and occlusive vasculitis was rare. In the short term, brolucizumab injection effectively improved vision at 1 month and dried retinal fluid for 3 months.

Real-World Treatment Intensity and Patterns in Patients With Myopic Choroidal Neovascularization: Common Data Model in Ophthalmology.

BACKGROUND: A paucity of data addressing real-world treatment of myopic choroidal neovascularization (mCNV) in the era of anti-vascular endothelial growth factor (VEGF) drugs led us to investigate real-world treatment intensity and treatment patterns in patients with mCNV. METHODS: This is a retrospective, observational study using the Observational Medical Outcomes Partnership-Common Data Model database of treatment-naïve patients with mCNV over the 18-year study period (2003-2020). Outcomes were treatment intensity (time trends of total/average number of prescriptions, mean number of prescriptions in the first year and the second year after initiating treatment, proportion of patients with no treatment in the second year) and treatment patterns (subsequent patterns of treatment according to the initial treatment). RESULTS: Our final cohort included 94 patients with at-least 1-year observation period. Overall, 96.8% of patients received anti-VEGF drugs as first-line treatment, with most of injections from bevacizumab. The number of anti-VEGF injections in each calendar year showed an increasing trend over time; however, there was a drop in the mean number of injections in the second year compared to the first year from 2.09 to 0.47. About 77% of patients did not receive any treatment in their second year of treatment regardless of drugs. Most of patients (86.2%) followed non-switching monotherapy only and bevacizumab was the most popular choice either in the first-line (68.1%) or in the second-line (53.8%) of treatment. Aflibercept was increasingly used as the first-line treatment for patients with mCNV. CONCLUSION: Anti-VEGF drugs have become the treatment of choice and second-line treatment for mCNV over the past decade. Anti-VEGF drugs are effective for the treatment of mCNV as the non-switching monotherapy is the main treatment regimen in most cases and the number of treatments decreases significantly in the second year of treatment.

Laser and anti-vascular endothelial growth factor treatment for drusenoid pigment epithelial detachment in age-related macular degeneration: 24-month outcomes.

PURPOSE: After the 12-month interim safety analysis, we investigated the 24-month primary endpoint outcomes of drusenoid pigment epithelial detachment (dPED) after laser and intravitreal anti-VEGF treatment. METHODS: Twenty-one patients with treatment-naïve bilateral intermediate AMD with dPED and visual acuity ≤ 83 letters (Snellen 20/23) were enrolled. The subject eye received low-energy PASCAL® laser (532 nm) treatment, and the fellow eye was used as the control. Intravitreal injections were administered at 3-month intervals from baseline to 12 months. Treatment outcomes, safety and development of advanced AMD lesions were analyzed. RESULTS: The mean drusen area and dPED height were significantly reduced (17.3 ± 2.7% vs. 112.8 ± 3.1%, P < 0.001 and 11.8 ± 4.7% vs. 119.1 ± 4.6%, P < 0.001, respectively) and the mean BCVA improved (5.11 ± 1.35 vs. 0.83 ± 1.03 letters, P = 0.014) in the study eyes compared to those in the control eyes. Development of parafoveal iRORA (nGA) (67%, 12 of 18 eyes) and cRORA (GA) (22%, 4 of 18 eyes) was observed in the study eyes, whereas three cases of iRORA and cRORA in the control eyes (17%, 3 of 18 eyes; P = 0.010 and P = 0.791, respectively). CONCLUSIONS: Laser and anti-VEGF treatment may be a potential treatment option for intermediate AMD with dPED. However, considering the relatively high rate of secondary iRORA and cRORA development, long-term follow-up is mandatory to clarify the safety and efficacy of this treatment.

PERIPAPILLARY MICROVASCULATURE OF THE RETINA AND CHORIOCAPILLARIS IN UNINVOLVED FELLOW EYES OF UNILATERAL RETINAL VEIN OCCLUSION PATIENTS.

PURPOSE: To investigate peripapillary microvascularity of the retina and choriocapillaris in uninvolved fellow eyes of patients with branch retinal vein occlusion (RVO) compared with that of healthy controls. METHODS: Peripapillary optical coherence tomography angiography bilateral eye scans of 46 patients with unilateral RVO and 46 age-matched control eyes were reviewed. Microvascular density in radial peripapillary capillary plexus (RPCP), superficial capillary plexus, and deep capillary plexus and signal void parameters in choriocapillaris were assessed. Data were statistically adjusted for hypertension. RESULTS: Microvascular densities in the RPCP and superficial capillary plexus were lower in the fellow eyes of patients with RVO than in the controls (RPCP, P = 0.021; superficial capillary plexus, P = 0.040). There were fewer choriocapillaris signal voids in the fellow eyes than in the control (P = 0.043). In patients with a duration of RVO onset >12 months (n = 27), all signal void parameters were lower in the fellow eyes than in the control eyes (size, P = 0.03; number, P = 0.046; proportion of the total area, P = 0.029). CONCLUSION: Uninvolved fellow eyes of patients with unilateral RVO showed microvascular impairment in the retina and choriocapillaris, even after adjusting for age and hypertension, suggesting that an unknown systemic factor might affect both the affected and unaffected eyes.

NASAL CROWDING AND NASAL TILTING OF THE MACULA AFTER EPIRETINAL MEMBRANE SURGERY.

PURPOSE: To identify postoperative macula deviation after epiretinal membrane surgery and to investigate its clinical effects. METHODS: Patients who underwent idiopathic epiretinal membrane removal and followed up for >12 months were enrolled. Macular deviation was evaluated using disk margin-to-fovea distance, foveal angle, and horizontal and vertical asymmetry of retinal thickness and volume. Horizontal or vertical asymmetry was defined as percentile asymmetry between nasal and temporal quadrants or between superior and inferior quadrants, respectively. The association between macular deviation parameters and best-corrected visual acuity and metamorphopsia were evaluated. Baseline and postoperative parameters were compared depending on epiretinal membrane severity. RESULTS: Data from 102 eyes with a mean follow-up of 21.14 months were analyzed. Disk margin-to-fovea distance and foveal angle decreased with time and horizontal asymmetry of thickness and volume increased with time, showing nasal crowding and nasal tilting. Postoperative changes of disk margin-to-fovea distance and horizontal asymmetry were associated with best-corrected visual acuity. Severe epiretinal membrane eyes showed greater postoperative nasal deviation than mild epiretinal membrane eyes. CONCLUSION: Postoperative nasal crowding and tilting was quantitatively identified. The causative layers for nasal deviation might be the inner retinal layers, as the foveal angle decreased with time. Postoperative disk margin-to-fovea distance shortening and nasal-deviated horizontal asymmetry were correlated with best-corrected visual acuity improvement.

Efficacy and safety of primary posterior capsulotomy during phaco-vitrectomy for epiretinal membrane.

PURPOSE: To evaluate the necessity and safety of primary posterior capsulotomy during phaco-vitrectomy for idiopathic epiretinal membrane (ERM). SETTING: Seoul National University Bundang Hospital, Seongnam, Korea. DESIGN: Retrospective consecutive cohort analysis. METHODS: This study enrolled 219 patients (228 eyes) who underwent combined 25-gauge phaco-vitrectomy for idiopathic ERM and cataract, divided into capsulotomy (-) group (152 eyes, 144 patients) and capsulotomy (+) group (76 eyes, 75 patients). The main outcomes were rate of posterior capsular opacity (PCO) occurrence and postoperative complications. Ophthalmic examinations were performed at baseline, 1, 3, 6, and 12 months postoperatively. RESULTS: PCO only occurred in capsulotomy (-) group (20 eyes, 13.2%), with mean onset of 10.59 months. Visually-significant PCO that needed Nd:YAG posterior capsulotomy was present in 9 eyes (45.0% of PCO eyes). The rate of cystoid macular edema (CME) was higher in capsulotomy (+) group (6.6% vs. 15.8%, p = 0.026) with longer duration (1.50 vs. 3.36 months, p = 0.019). Female sex and posterior capsulotomy were significant risk factors for CME occurrence (p < 0.05). CONCLUSION: Primary posterior capsulotomy during phaco-vitrectomy for idiopathic ERM obviated the need for Nd:YAG posterior capsulotomy, but visually-significant PCO that needed Nd:YAG laser was not common. Considering the low rate of visually-significant PCO and high rate of postoperative CME, routine posterior capsulotomy during phaco-vitrectomy may not be necessary for preventing PCO in ERM.

Localized versus 360-degree laser photocoagulation with limited pars plana vitrectomy in the management of primary rhegmatogenous retinal detachment.

BACKGROUND: To compare the efficacy of intraoperative localized and 360-degree laser photocoagulation in 23-gauge limited pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment (RRD). METHODS: This retrospective, comparative, consecutive, interventional study included 155 eyes of 155 patients who underwent primary repair of RRD utilizing 23-gauge PPV with at least six months of follow up. Medical records were retrospectively reviewed, and the corresponding demographic data, preoperative ophthalmic features, surgical management, and postoperative course were recorded. Main outcome measures included single surgery anatomical success, pre- and post-operative visual acuity, and complications. RESULTS: Eighty-three patients (group A) received localized laser photocoagulation in PPV, while the remaining 72 patients (group B) received underwent circumferential 360-degree laser photocoagulation in PPV. Two skilled-surgeons performed all the surgeries, and 23-gauge PPV instrumentation, a wide-angle viewing system, endolaser photocoagulation, and gas tamponade were used in each case. No significant difference was identified in baseline characteristics. The single surgery anatomical success rate was 96.4 % in group A, and 95.8 % in group B, showing no significant difference (p = 1.00). Primary anatomical failure was caused by re-detachment due to break in 2 eyes in each group (no new break 1 eye, new break 1eye in group A, 2 eyes with no new break in group B), and proliferative vitreoretinopathy in 1 eye in each group. Other complications were epiretinal membrane in 7 eyes (3 in group A, 4 in group B), and macular hole in 1 eye in group B. There were no differences in pre- and post-operative best-corrected visual acuity (BCVA) as well as BCVA improvement (p=0.144, p=0.866 and p=0.263, respectively). CONCLUSION: Localized laser photocoagulation showed no difference in anatomic and visual outcome in RRD patients, when compared with 360-degree laser photocoagulation in limited PPV. Routine circumferential 360-degree laser photocoagulation may not be necessary in vitrectomy surgery for primary rhegmatogenous retinal detachment without severe PVR.

Use of OCT Retinal Thickness Deviation Map for Hydroxychloroquine Retinopathy Screening.

PURPOSE: To investigate the use of a retinal thickness deviation map generated from swept-source (SS) OCT images for hydroxychloroquine retinopathy screening. DESIGN: Retrospective cohort study. PARTICIPANTS: This study included 1192 Korean patients with a history of hydroxychloroquine treatment: 881 patients (1723 eyes) in the discovery set and 311 patients (591 eyes) in the validation set. Patients were screened for retinal toxicity using SS OCT, fundus autofluorescence, and standard automated perimetry. METHODS: According to the 2016 American Academy of Ophthalmology guidelines, hydroxychloroquine retinopathy was diagnosed by the presence of abnormalities on ≥1 objective structural tests alongside corresponding visual field defects. The 12 × 9-mm2 macular volume SS OCT scan was performed, and the retinal thickness deviation map was generated automatically using the built-in software. On this map, yellow (retinal thickness, <5% of the normative level) or red (<1% of the normative level) pixels were defined as abnormal. Abnormal findings were evaluated, and diagnostic criteria were developed based on the discovery set data; criteria were validated using the validation set data. MAIN OUTCOME MEASURES: The rate and patterns of abnormalities on the retinal thickness deviation map and sensitivity and specificity of the diagnostic criteria. RESULTS: The retinal thickness deviation map showed the following abnormal patterns in eyes with hydroxychloroquine retinopathy: pericentral (36.0%) or parafoveal (6.1%) ring, mixed-ring (34.2%), central island (13.2%), and whole macular thinning (10.5%). The criterion of ≥5 contiguous red pixels showing 1 of the 5 characteristic patterns in both eyes yielded the greatest diagnostic performance (sensitivity and specificity of 98.2% and 89.1% and of 100% and 87.5% in the discovery and validation set data, respectively). Moreover, the area of abnormal pixels on the map was correlated significantly with the mean deviation (P < 0.001) and pattern standard deviation (P < 0.001) on the Humphrey 30-2 test in eyes with hydroxychloroquine retinopathy. CONCLUSIONS: The retinal thickness deviation map may facilitate the objective evaluation of hydroxychloroquine retinopathy because it does not require subjective, morphologic evaluation of the outer retinal layers. The map has the potential to enhance hydroxychloroquine retinopathy screening when used in conjunction with conventional screening methods.

AICAR upregulates ABCA1/ABCG1 expression in the retinal pigment epithelium and reduces Bruch's membrane lipid deposit in ApoE deficient mice.

The etiology of age-related macular degeneration (AMD) is diverse; however, recent evidence suggests that the lipid metabolism-cholesterol pathway might be associated with the pathophysiology of AMD. The ATP-binding cassette (ABC) transporters, ABCA1 and ABCG1, are essential for the formation of high-density lipoprotein (HDL) and the regulation of macrophage cholesterol efflux. The failure of retinal or retinal pigment epithelium (RPE) cholesterol efflux to remove excess intracellular lipids causes morphological and functional damage to the retina. In this study, we investigated whether treatment with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), an AMP-activated protein kinase (AMPK) activator, improves RPE cholesterol efflux and Bruch's membrane (BM) lipid deposits. The protein and mRNA levels of ABCA1 and ABCG1 in ARPE-19 cells and retinal and RPE/choroid tissue from apolipoprotein E-deficient (ApoE-/-) mice were evaluated after 24 weeks of AICAR treatment. The cholesterol efflux capacity of ARPE-19 cells and the cholesterol-accepting capacity of apoB-depleted serum from mice were measured. The thickness of the BM and the degree of lipid deposition were evaluated using electron microscopy. AICAR treatment increased the phosphorylation of AMPK and the protein and mRNA expression of ABCA1 and ABCG1 in vitro. It promoted cholesterol efflux from ARPE-19 cells and upregulated the protein and mRNA levels of ABCA1 and ABCG1 in the retina and RPE in vivo. ApoB-depleted serum from the AICAR-treated group showed enhanced cholesterol-accepting capacity. Long-term treatment with AICAR reduced BM thickening and lipid deposition in ApoE-/- mice. In conclusion, AICAR treatment increased the expression of lipid transporters in the retina and RPE in vivo, facilitated intracellular cholesterol efflux from the RPE in vitro, and improved the functionality of HDL to accept cholesterol effluxed from the cell, possibly via AMPK activation. Collectively, these effects might contribute to the improvement of early age-related pathologic changes in the BM. Pharmacological improvement of RPE cholesterol efflux via AMPK activation may be a potential treatment strategy for AMD.

TEMPORAL CHANGES OF PARAFOVEAL MICROVASCULATURE AFTER EPIRETINAL MEMBRANE SURGERY: An Optical Coherence Tomography Angiography Study.

PURPOSE: To investigate whether the parafoveal capillary architecture predicts clinical course and visual outcomes after epiretinal membrane (ERM) surgery. METHODS: A total of 71 eyes of 71 patients treated with vitrectomy for idiopathic ERM were enrolled. The parafoveal capillary displacement and fractal geometries were compared according to the stage of ERM. Correlations between the parafoveal capillary displacement in the superficial capillary plexus, the fractal dimension and lacunarity in the deep capillary plexus (DCP), foveal thickness, and visual outcomes were evaluated. RESULTS: Compared with eyes with mild ERM, eyes with severe ERM exhibited higher parafoveal capillary displacement in the superficial capillary plexus, lower fractal dimension and higher lacunarity in the DCP, and greater foveal thickness (P < 0.05). The parafoveal capillary displacement in the superficial capillary plexus and fractal dimension and lacunarity in the DCP improved significantly, particularly at 1 month postoperatively (P < 0.05) and reached a plateau thereafter. The preoperative fractal dimension in the DCP showed a significant correlation with the best-corrected visual acuity at all follow-up time points (P < 0.05). CONCLUSION: The parafoveal fractal dimension in the DCP was significantly correlated with the visual acuity before and after ERM surgery. The parafoveal fractal dimension may serve as a predictive marker for visual outcomes after ERM surgery.

PHACOVITRECTOMY VERSUS LENS-SPARING VITRECTOMY FOR RHEGMATOGENOUS RETINAL DETACHMENT REPAIR ACCORDING TO THE SURGICAL EXPERIENCE.

PURPOSE: To compare the efficacy and safety between lens-sparing vitrectomy and phacovitrectomy for primary rhegmatogenous retinal detachment treatment according to surgical experience. METHODS: We retrospectively reviewed the medical records of 193 patients with primary rhegmatogenous retinal detachment who underwent either lens-sparing vitrectomy (n = 111) or phacovitrectomy (n = 82). Patients were operated by two experienced surgeons or eight vitreoretinal fellows and had a minimum follow-up of 6 months. Anatomical success rate, postoperative complications, and functional outcomes were compared. RESULTS: Primary anatomical success rate was 92.8% (103/111) for lens-sparing vitrectomy and 91.5% (75/82) for phacovitrectomy (P = 0.733). The fellows had lower success rate after phacovitrectomy compared with the experts, but not statistically significant (85% [34/40] vs. 97.6% [41/42], P = 0.054). During phacovitrectomy, one zonulysis case in the experts group and four posterior capsular rupture cases in the fellows group were noted. Cystoid macular edema was found only after phacovitrectomy (12.2% [10/82]), and epiretinal membrane occurred more after phacovitrectomy than after lens-sparing vitrectomy (28% [23/82] vs. 8.1% [9/111], P < 0.001). There was no difference in the occurrence of cystoid macular edema and epiretinal membrane after phacovitrectomy between two surgeon groups (P = 0.514, 0.701, respectively). CONCLUSION: Combined phacoemulsification and vitrectomy has no additional benefit in improving the surgical outcome of primary rhegmatogenous retinal detachment management. Considering the intraoperative and postoperative complications and the relatively low success rate, phacovitrectomy may not be a desirable option in inexperienced surgeons.