Displacement of Submacular Hemorrhage Using Subretinal Cocktail Injection versus Pneumatic Displacement: A Real-World Comparative Study.

INTRODUCTION: The objective of this study was to compare the outcome of submacular hemorrhage (SMH) displacement using pneumatic displacement with intravitreal expansile gas versus pars plana vitrectomy (PPV) with subretinal injection of tissue plasminogen activator (tPA), anti-vascular endothelial growth factor (VEGF) agent, and air as primary surgery. METHODS: Retrospective interventional case series of 63 patients who underwent surgical displacement of SMH secondary to neovascular age-related macular degeneration (nAMD) or polypoidal choroidal vasculopathy (PCV) from May 1, 2015, to October 31, 2022. Medical records were reviewed for diagnosis, logMAR visual acuity (VA), central subfield thickness (CST), and postoperative displacement rates and complications up to 12 months after operation. RESULTS: The diagnosis was nAMD in 24 (38.1%) and PCV in 39 (61.9%) eyes. There were 40 (63.5%) eyes in the pneumatic displacement group (38 received C3F8, 2 received SF6) and 23 (36.5%) eyes in the subretinal cocktail injection. Mean baseline VA was 1.46 and 1.62, respectively (p = 0.404). The subretinal injection group had more extensive SMH (p = 0.005), thicker CST (1,006.6 µm vs. 780.2 µm, p = 0.012), and longer interval between symptom and operation (10.65 vs. 5.53 days, p < 0.001). The mean postoperative VA at 6 months was 0.67 and 0.91 (p = 0.180) for pneumatic displacement and subretinal injection groups, respectively, though VA was significantly better in the pneumatic group at 12-month visit (0.64 vs. 1.03, p = 0.040). At least 10 mean change in VA were >10 letters gain in both groups up to 12 months. Postoperative CST reduction was greater (625.1 µm vs. 326.5 µm, p = 0.008) and complete foveal displacement (87.0% vs. 37.5%), p < 0.001, odds ratio [OR] = 11.1) and displacement to arcade or beyond (52.5% vs. 17.5%, p = 0.009, OR = 5.15) were more frequent in the subretinal injection group. Two patients with failed pneumatic displacement were successfully treated with subretinal cocktail injection as a second operation. CONCLUSION: Surgical displacement of SMH leads to clinically meaningful improvement in VA. PPV with subretinal cocktail injection is more effective than pneumatic displacement in displacing SMH with similar safety profile despite longer interval before operation, higher CST, and more extensive SMH at baseline. Retinal surgeons could consider this novel technique in cases with thick and extensive SMH or as a rescue secondary operation in selected cases.

COMPARING FUNCTIONAL AND VASCULAR LAYER OUTCOMES OF LASER PHOTOCOAGULATION VERSUS SUBTHRESHOLD MICROPULSE LASER FOR DIABETIC MACULAR EDEMA: An OCT-Angiography Study.

PURPOSE: To compare the efficacy of conventional laser and subthreshold micropulse laser (SML) in treating diabetic macular edema in terms of functional outcomes and changes in quantitative metrics for the retinal capillary and choriocapillary vascular layers. METHODS: Fifty-two eyes from 52 patients with treatment-naive, clinically significant macular edema were randomly assigned to the conventional laser group or SML group in a 1:1 ratio. Best-corrected visual acuity, central macular thickness (CMT), and optical coherence tomography angiography scans were measured at baseline, 1, 3, and 6 months after treatment. RESULTS: The SML group showed rapid visual recovery, improving from baseline of 0.320 ± 0.31 logarithm of the minimum angle of resolution (20/42 Snellen) to 0.270 ± 0.22 logarithm of the minimum angle of resolution (20/37 Snellen) at 1 month ( P = 0.038) and had significant improvements in CMT at 6-month post-treatment (353.88-301.00 µ m, P = 0.005). Statistically significant changes were detected across all optical coherence tomography angiography metrics, including vessel density, vessel length density, vessel diameter index, and fractal dimension, at 6 months for both groups in the deep capillary plexus and choriocapillary plexus. CONCLUSION: Subthreshold micropulse laser resulted in early visual recovery and sustained macular thickness improvement in the treatment of diabetic macular edema. Microvascular perfusion parameters, including vessel density, vessel length density, and fractal dimension, improved in the deep capillary plexus and choriocapillary plexus for both treatment groups at 6 months post-treatment.

Intraocular inflammation following COVID-19 vaccination: the clinical presentations.

PURPOSE: The purpose of the study was to describe the cases of intraocular inflammation following COVID-19 vaccination (Comirnaty mRNA vaccine and CoronaVac vaccine) in Hong Kong. METHODS: This was a retrospective case series. RESULTS: This series includes 16 eyes among 10 female patients, with a mean age of 49.4 ± 17.4 years. Eight patients (80%) received the Pfizer-BioNTech mRNA vaccination. Anterior uveitis was the most common presentation of postvaccination uveitis (50%) observed in our series, followed by intermediate uveitis (30%) and posterior uveitis (20%), respectively. A case of retinal vasculitis in the form of frosted branch angiitis, previously only reported following COVID-19 infection, was observed following COVID-19 vaccination. The median time from vaccination to uveitis onset was 15.2 days (range: 0-6 weeks). Inflammation in 11 out 16 eyes (68.75%) was completely resolved with topical steroids. CONCLUSION: Anterior uveitis was the predominant presentations of uveitis flare-ups following COVID-19 in our case series, followed by intermediate uveitis. Aligning with the current global literature concerning this issue, most of the uveitis attacks presented as anterior uveitis and were completely resolved with topical steroids. Consequently, the risk of uveitis flare-ups should not deter the public from receiving COVID-19 vaccines.

Untargeted metabolomic analysis of aqueous humor in diabetic macular edema.

Background: The mechanism of diabetic macular edema (DME) was explored by comparing the intraocular metabolite profiles of the aqueous humor of patients with DME to those of diabetic patients without DME using untargeted metabolomic analysis. Methods: Aqueous samples from 18 type 2 diabetic patients with DME and 18 type 2 diabetic patients without DME used as controls were analyzed using liquid chromatography-mass spectrometry (LCMS). The two groups of patients were age and gender matched and had no systemic diseases other than diabetes mellitus (DM). The metabolites were analyzed using orthogonal partial least square discriminant analysis. Results: The metabolite profiles in DME patients differed from those in DM controls. This indicates the following metabolic derangements in DME: (a) a higher amount of oxidized fatty acids but a lower amount of endogenous antioxidants (oxidative stress); (b) higher levels of ß-glucose and homocysteine but a lower level of sorbitol (hyperglycemia); (c) a higher amount of prostaglandin metabolites (inflammation); (d) higher amounts of acylcarnitines, odd-numbered fatty acids, and 7,8-diaminononanoate (respiration deterioration); (e) a higher amount of neurotransmitter metabolites and homovanillic acid (neuronal damage); (f) a lower amount of extracellular matrix (ECM) constituents (ECM deterioration); and (g) a higher amount of di-amino peptides (microvascular damage). Conclusions: The change in the metabolic profiles in the aqueous humor of DME patients compared to DM controls without DME indicates that DME patients may have less capability to resist various stresses or damaging pathological conditions, such as oxidative stress, mitochondrial insufficiency, inflammation, and ECM deterioration.

The clinical presentation and treatment outcomes of ocular tuberculosis: a 5-year experience in an endemic area.

PURPOSE: To report the clinical presentations of ocular tuberculosis infection (OTB) and the treatment regimen and outcome in an endemic area. METHODS: This is a retrospective case series of patients with presumed OTB treated in a tertiary teaching hospital in Hong Kong in 2014-2019. RESULTS: Among the nineteen patients recruited, the most common clinical presentation of OTB was retinal vasculitis (42.1%), followed by scleritis, intermediate uveitis, and choroidal tuberculoma (15.8% respectively). 94.7% and 94.4% of the subjects were treated with ATT and steroid, respectively, and 31.6% were put on systemic immunosuppressant prior to the initiation of ATT. Apart from those suffering from intermediate uveitis, most demonstrated good clinical response within 8 weeks of ATT initiation. CONCLUSION: Ocular involvement of TB has been increasingly recognized, especially in endemic regions like Hong Kong. High index of suspicion is recommended for OTB in typical clinical phenotypes or recurrent/resistant ocular inflammation unresponsive to conventional therapy. TB retinal vasculitis was the most common presentation of OTB in this study and OTB generally requires treatment with either regional or systemic steroid together with ATT.

Identification and characterization of a novel promoter variant in placental growth factor for neovascular age-related macular degeneration.

PURPOSE: Intronic variants in the placental growth factor (PGF) gene have been associated with neovascular age-related macular degeneration (AMD). This study is to discover and characterize rare variants in the PGF gene for neovascular AMD. METHODS: The promoter region, coding sequences and splicing regions of the PGF gene were sequenced in a Hong Kong southern Chinese cohort of 235 neovascular AMD patients and 435 controls. A detected 18 base-pair deletion variant in the promoter region of PGF was analyzed in a Shantou southern Chinese cohort of 189 neovascular AMD patients and 846 controls. The transcription activity of this disease-associated promoter variant was determined in human ARPE-19 cells by promoter-luciferase analysis. RESULTS: A novel 18-base-pair deletion mutation in the promoter region of PGF was identified in 3 (1.28%) patients and 1 (0.23%) control subject (OR = 5.61; 95% CI 0.58-54.26) in the Hong Kong cohort, and in 2 (1.06%) patients and 2 (0.24%) controls (OR = 4.51; 95% CI: 0.63-32.25) in the Shantou cohort. In the combined southern Chinese sample, this deletion had a significant association with neovascular AMD (P = 0.026; OR = 5.08, 95% CI: 1.21-21.36). The 18-base-pair deletion was predicted to alter the transcription factor binding sites in the PGF promoter, and higher luciferase expression was detected in ARPE-19 cells transfected with the deletion variant plasmid than those transfected with wild type plasmid (P = 0.0002). CONCLUSIONS: This study identified a rare, functional promoter variant in the PGF gene that increases PGF transcription activity and confers a 5-fold risk to neovascular AMD.

Improving the quality of electroretinogram recordings using active electrodes.

The aim of this study was to compare the quality of electroretinogram (ERG) recordings using a custom built active electrode with attached amplifier versus a standard (passive) ERG electrode. Scotopic and photopic ERG responses were recorded from five adult albino rabbits using a custom built active electrode on one eye and a passive electrode on the other. For the active electrode, the ERG-jet electrode (Universo S.A., La Chaux-De-Fonds, Switzerland) was used as the transducer with the cable cut short and soldered directly to the input of a customized amplifier. The passive electrode was a standard ERG jet electrode. The signal to noise ratio and reproducibility of ERGs were compared. The noise was significantly lower in the active electrode compared to the passive electrode (p = 0.009) resulting in signals being recorded at lower stimulation strengths with the active electrode. The scotopic a-wave was significantly larger in the active electrode at all supra-threshold stimulation intensities (p < 0.05) and the scotopic b-wave amplitudes were also higher in the active electrode at all supra-threshold stimulation intensities but was only statistically significant between -3.25 and -1 log cd.s.m-2 (p < 0.05). The photopic a- and b-wave amplitudes were also higher in the active electrode and statistically significant between -0.75 and 0.48 log cd.s.m-2 for the a-wave and -1.25 to -1 log cd.s.m-2 for the b-wave (p < 0.05). The intra-observer repeatability, inter-sessions reproducibility and reliability of the signals were better in the active electrode as evidenced by lower coefficient of variation (CV) and coefficient of repeatability (CR) with high intra-class correlation coefficient (ICC) of the a- and b-wave parameters of the active electrode. These findings suggest that the custom built active ERG electrode produces less noise than the passive electrode, allowing responses to be recorded at lower stimulation strengths. It produces greater signal amplitudes and improved reproducibility and is therefore a better device for investigating retinal function.

Bilateral acute retinal necrosis after bilateral cataract surgery in an immunocompromised patient: a case report.

PURPOSE: To report a case of bilateral varicella zoster virus (VZV)-associated acute retinal necrosis (ARN) occurring after both eyes sequential cataract surgery in an elderly immunocompromised patient. METHODS: Medical records and investigation results of the patient were reviewed. RESULTS: Patient experienced floaters and blurring of vision in both eyes 4 weeks after her second uncomplicated cataract surgery. Clinical signs of granulomatous keratic precipitates, prominent vitritis, retinitis and vascular thrombosis were noted in both eyes. Aqueous samples from both eyes were positive for VZV. Disease was treated with intravitreal foscarnet bilaterally and 10 days of systemic intravenous acyclovir (10 mg/kg) followed by oral valaciclovir 1 g three times daily. Final visual acuity at 4 months after initial presentation was 20/60 in both eyes with no retinal detachment noted. CONCLUSIONS: Cataract surgery may have been the trigger for bilateral VZV-associated ARN. Immunocompromised patients can develop ARN and require close observation after cataract surgery. This is, to our knowledge, the first report of bilateral ARN following routine cataract surgery.

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.

Change in flash visual evoked potentials in New Zealand albino rabbits after sub-tenon's anesthesia.

CONTEXT: The occurrence of amaurosis during ophthalmic anesthesia is well known. The reason for this manifestation has not been studied. PURPOSE: To investigate the effect of sub-tenon's anesthesia on visual conduction in rabbit eyes. METHODS: Fifteen right eyes of 15 New Zealand albino rabbits were included. 2% lidocaine hydrochloride and 0.75% bupivacaine hydrochloride (1 ml, 1:1 mixture) was injected in the sub-tenon's space of 8 eyes while the control group (n = 7) was injected with 1 ml physiological saline. Flash visual evoked potentials (FVEP) were performed with Roland reti-scan system before and, 5 min, 15 min, and 5 days after injection. The natural pupillary diameter and minimal pupillary diameter with light reflex were recorded. RESULTS: In the anesthesia group, N1 latency, P1 latency, and P1 amplitude were 17.13 ± 1.13 ms, 28.25 ± 1.83 ms, 13.45 ± 4.36 µv respectively before injection; 21.75 ± 3.06 ms, 29.63 ± 2.67 ms, 7.24 ± 4.64 µv at 5 min after injection; 22.25 ± 1.39 ms, 29.50 ± 2.51 ms, 7.54 ± 4.47 µv at 15 min after injection, and, 17.75 ± 0.71 ms, 28.13 ± 2.42 ms, 13.17 ± 4.08 µv 5 days after injection. When compared with baseline, N1 latency at 5 min and 15 min after injection showed prolongation (p = 0.019 and p = 0.001, respectively). Likewise, P1 amplitude decreased at 5 min and 15 min after injection (p < 0.001, p < 0.001, respectively). Both N1 latency and P1 amplitude recovered 5 days after the injection. Pupillary light reflex (PLR) constriction amplitude was 35.42% and 0.00% before and at 5 min after injection (p = 0.012). After 5 days it recovered to 33.33%. The FVEP and PLR constriction amplitude did not change significantly after injection in the control group. DISCUSSION: Sub-tenon's anesthesia was associated with changes in the FVEP and pupullary light reflex in rabbit eyes in our study. CONCLUSIONS: The data from this study suggested that sub-tenon's anesthesia could reversibly block visual conduction in rabbit's eyes.

Combined pars plana vitrectomy-scleral buckle versus pars plana vitrectomy for proliferative vitreoretinopathy.

The purpose of the study is to evaluate the surgical outcomes of combined pars plana vitrectomy-scleral buckle (PPV-SB) versus pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment complicated with proliferative vitreoretinopathy (PVR). One thousand one hundred and seventy four patients with rhegmatogenous retinal detachment surgery between January 2002 and December 2013 were retrospectively reviewed. Patients with grade C PVR treated with either combined PPV-SB or PPV alone were included in the study. Study outcomes included single surgery anatomic success rate and postoperative visual outcome at 12 months postoperatively. Seventy-seven patients with grade C PVR were identified for analysis. At the end of 12-month follow-up, 80.5 % eyes (33/41) in the PPV-SB group and 58.3 % eyes (21/36) in the PPV group achieved single surgery anatomical success. In a multiple logistic regression model, none of the baseline variables (age, gender, macula status, grade of PVR, extent of detachment, presence of vitreous hemorrhage, lens status, status of high myopia) nor types of retinal detachment surgery (use of scleral buckle, barrier endolaser, 360 degree endolaser, cryopexy, retinectomy, tamponade agent, phacoemulsification) had significant effect on single surgery anatomical success. The post-treatment mean logMAR visual acuity of the PPV-SB group was 1.58 ± 0.58 and the PPV group was 1.57 ± 0.61. There was no significant difference in the postoperative visual acuity between the two groups (P = 0.849). For patients with grade C PVR, PPV-SB did not demonstrate a superiority over PPV alone in achieving single surgery anatomical success.

Association of Genetic Variants with Polypoidal Choroidal Vasculopathy: A Systematic Review and Updated Meta-analysis.

TOPIC: A systematic review and meta-analysis of the genetic association with polypoidal choroidal vasculopathy (PCV) and the genetic difference between PCV and neovascular age-related macular degeneration (nAMD). CLINICAL RELEVANCE: To identify genetic biomarkers that are potentially useful for genetic diagnosis of PCV and for differentiating PCV from nAMD. METHODS: We performed a literature search in EMBASE, PubMed, Web of Science, and the Chinese Biomedical Database for PCV genetic studies published before February 6, 2015. We then conducted a meta-analysis of all polymorphisms that had sufficient genotype/allele data reported in ≥2 studies and estimated the summary odds ratio (OR) and 95% confidence intervals (CIs) for PCV. We also compared the association profiles between PCV and nAMD, and performed a sensitivity analysis. RESULTS: A total of 66 studies were included in the meta-analysis, involving 56 polymorphisms in 19 genes/loci. In total, 31 polymorphisms in 10 genes/loci (age-related maculopathy susceptibility 2 [ARMS2], high-temperature requirement factor A1 [HTRA1], complement factor H [CFH], complement component 2 [C2], CFB, RDBP, SKIV2L, CETP, 8p21, and 4q12) were significantly associated with PCV. Another 25 polymorphisms in 13 genes (ARMS2, HTRA1, C2, CFB, ELN, LIPC, LPL, ABCA1, VEGF-A, TLR3, LOXL1, SERPING1, and PEDF) had no significant association. Twelve polymorphisms at the ARMS2-HTRA1 locus showed significant differences between PCV and nAMD. The sensitivity analysis validated the significance of our analysis. CONCLUSIONS: This study revealed 31 polymorphisms in 10 genes/loci that contribute to PCV susceptibility. Among them, ARMS2-HTRA1 also showed allelic diversity between PCV and nAMD. Our results confirm the gene variants that could affect the phenotypic expressions of PCV and nAMD.

Genetic association of TIE2 with diabetic retinopathy and diabetic macular edema.

PURPOSE: To evaluate the associations of the TIE2 gene with diabetic retinopathy (DR) and diabetic macular edema (DME). METHODS: This study included a Chinese cohort of 285 non-proliferative DR patients and 433 healthy controls. The DR patients were classified further into those with or without DME. Thirty haplotype-tagging single-nucleotide polymorphisms (SNPs) in TIE2 were genotyped using TaqMan technology. Associations of DR and subtypes were analyzed by logistic regression adjusted for age and sex. Stratification association analysis by sex was performed. RESULTS: TIE2 rs625767 showed a nominal but consistent association with DR [odds ratio (OR) = 0.71, P = 0.005] and subtypes (DR without DME: OR = 0.69, P = 0.016; DME: OR = 0.73, P = 0.045). SNP rs652010 was consistently associated with overall DR (OR = 0.74, P = 0.011) and DR without DME (OR = 0.70, P = 0.016), but not with DME. Moreover, SNPs rs669441, rs10967760, rs549099 and rs639225 showed associations with overall DR, whilst rs17761403, rs664461 and rs1413825 with DR without DME. In stratification analysis, three SNPs, rs625767 (OR = 0.62, P = 0.005), rs669441 (OR = 0.63, P = 0.006) and rs652010 (OR = 0.64, P = 0.007), were associated with DR in females, but not in males. Moreover, one haplotype T-T defined by rs625767 and rs669441 was significantly associated with DR in females only. CONCLUSIONS: This study revealed TIE2 as a susceptibility gene for DR and DME in Chinese, with a sex-specific association in females. Further validation should be warranted.

Risk factors for diabetic retinopathy, diabetic macular edema, and sight-threatening diabetic retinopathy.

OBJECTIVE: To identify the risk factors for the development of diabetic retinopathy (DR), diabetic macular edema (DME), and sight-threatening DR (STDR) based on a city-wide diabetes screening program. RESEARCH DESIGN AND METHODS: Diabetic patients were prospectively recruited between June 2016 and December 2022. All patients underwent dilated fundus photography centered on the disc and macula or macular spectral domain optical coherence tomography (SD-OCT) scan. Complete medical history was documented. Systematic examination, blood analysis, and urinalysis were performed. Multivariate logistic regression analysis adjusting for age and sex was conducted. RESULTS: Out of 7274 diabetic patients, 6840 had gradable images, among which 3054 (42.0%) were graded as DR, 1153 (15.9%) as DME, and 1500 (20.6%) as STDR. The factors associated with DR, DME, and STDR included younger age (odds ratio [OR]: 0.96, 0.97, and 0.96 respectively), lower BMI (OR: 0.97, 0.95, and 0.95 respectively), longer duration of diabetes (OR: 1.07, 1.03, and 1.05 respectively) and positive of urinary albumin (OR: 2.22, 2.56, and 2.88 respectively). Other associated factors included elevated blood urea nitrogen (OR: 1.22, 1.28, and 1.27 respectively), higher LDL-cholesterol, lower blood hemoglobin (OR: 0.98, 0.98, and 0.98), insulin intake, presence of diabetic foot pathologies and diabetic peripheral neuropathy. We also identified novel risk factors, including high serum potassium (OR: 1.37, 1.46, and 1.55 respectively), high-serum sodium (OR: 1.02, 1.02, and 1.04 respectively). Better family income was a protective factor for DR, DME, and STDR. Alcohol consumption once a week was also identified as a protective factor for DR. CONCLUSIONS: Similar risk factors for DR, DME, and STDR were found in this study. Our data also indicates high serum sodium, high serum potassium, low blood hemoglobin, and level of family income as novel associated factors for DR, DME, and STDR, which can help with DR monitoring and management.

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

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

Performance, safety and efficiency comparison between 10,000 and 5000 cuts per minute vitrectomy using a 25G cutter: a prospective randomized controlled study.

PURPOSE: This study aims to compare the performance of the 25+® UltraVit® 5000 cuts per minute (cpm) vitrectomy probe versus the 25+ ® Ultravit 10,000 cpm® beveled tip, dual drive vitrectomy probe. METHOD: In this prospective randomised controlled clinical trial, 52 eyes of 52 consecutive patients were randomized into either the 10,000 cpm (25 patients) or 5000 cpm vitrectomy group (27 patients). Patients were evaluated preoperatively, intraoperatively, and postoperatively on the first day, and at 1 week, 1 month and 3 months. The main outcome measures were vitrectomy time, and secondary endpoints were time to induction of posterior vitreous detachment, intraoperative complications, and number of instruments used. RESULTS: The vitrectomy time was shorter in the 10,000 cpm group (413.7 s) compared to the 5000 cpm group (463.4 s), although there was no significant difference (p = 0.5999). One patient had an iatrogenic retinal break in the 10,000 cpm group while two patients had an iatrogenic retinal break in the 5000 cpm group. The time for posterior vitreous detachment (PVD) induction and the number of instruments used were not significantly different between the two groups. CONCLUSION: The difference in vitrectomy times between the 10,000 cpm vitrectomy probe and the 5000 cpm cutter were not statistically significant. This may suggest that other factors affect efficiency rather than the limitations of equipment.

RIP3-mediated microglial necroptosis promotes neuroinflammation and neurodegeneration in the early stages of diabetic retinopathy.

Diabetic retinopathy (DR) is a leading cause of blindness that poses significant public health concerns worldwide. Increasing evidence suggests that neuroinflammation plays a key role in the early stages of DR. Microglia, long-lived immune cells in the central nervous system, can become activated in response to pathological insults and contribute to retinal neuroinflammation. However, the molecular mechanisms of microglial activation during the early stages of DR are not fully understood. In this study, we used in vivo and in vitro assays to investigate the role of microglial activation in the early pathogenesis of DR. We found that activated microglia triggered an inflammatory cascade through a process called necroptosis, a newly discovered pathway of regulated cell death. In the diabetic retina, key components of the necroptotic machinery, including RIP1, RIP3, and MLKL, were highly expressed and mainly localized in activated microglia. Knockdown of RIP3 in DR mice reduced microglial necroptosis and decreased pro-inflammatory cytokines. Additionally, blocking necroptosis with the specific inhibitor GSK-872 improved retinal neuroinflammation and neurodegeneration, as well as visual function in diabetic mice. RIP3-mediated necroptosis was activated and contributed to inflammation in BV2 microglia under hyperglycaemic conditions. Our data demonstrate the importance of microglial necroptosis in retinal neuroinflammation related to diabetes and suggest that targeting necroptosis in microglia may be a promising therapeutic strategy for the early stages of DR.

Mapping nanoscale topographic features in thick tissues with speckle diffraction tomography.

Resolving three-dimensional morphological features in thick specimens remains a significant challenge for label-free imaging. We report a new speckle diffraction tomography (SDT) approach that can image thick biological specimens with ~500 nm lateral resolution and ~1 µm axial resolution in a reflection geometry. In SDT, multiple-scattering background is rejected through spatiotemporal gating provided by dynamic speckle-field interferometry, while depth-resolved refractive index maps are reconstructed by developing a comprehensive inverse-scattering model that also considers specimen-induced aberrations. Benefiting from the high-resolution and full-field quantitative imaging capabilities of SDT, we successfully imaged red blood cells and quantified their membrane fluctuations behind a turbid medium with a thickness of 2.8 scattering mean-free paths. Most importantly, we performed volumetric imaging of cornea inside an ex vivo rat eye and quantified its optical properties, including the mapping of nanoscale topographic features of Dua's and Descemet's membranes that had not been previously visualized.

Acute postoperative endophthalmitis after cataract operation: result of early vitrectomy within 24 hours of presentation.

OBJECTIVES: To evaluate result of early pars plana vitrectomy (PPV) within 24 hours of presentation for acute postoperative endophthalmitis after cataract operation, and to determine factors that predict visual outcome. METHODS: Consecutive patients who developed acute postoperative endophthalmitis within 6 weeks after cataract operation were reviewed. Patients were divided into two groups for analysis: (1) those receiving PPV within 24 hours of presentation (early PPV group), and (2) those receiving initial intravitreal antibiotics only without PPV within 24 hours of presentation (IVA group). RESULTS: Out of 41,411 cataract operations, 22 eyes developed acute postoperative endophthalmitis. Presenting VA was hand-movement or worse in 72.7%. The most common organisms were Staphylococcus (40.9%), Streptococcus (13.6%) and Enterococcus (13.6%). 22.7% of eyes had good final VA ≥ 20/30 and 27.3% had poor final VA < 20/400. Early PPV group had significantly lower rate of requiring additional treatments to control infection (25% versus 80%, P = 0.030), higher rate of retinal detachment (25% versus 0%, P = 0.221) and similar final logMAR VA (1.08 ± 1.08 versus 0.80 ± 0.80, P = 0.489) compared to IVA. Multivariate linear regression analysis showed that worse final VA was significantly associated with Streptococcus (ß = 1.92, P = 0.007) and retinal detachment (ß = 1.72, P = 0.005) but not with early PPV (P = 0.225). CONCLUSION: Early PPV was superior to initial intravitreal antibiotics alone as it required fewer additional treatments to control infection. Visual outcome was similar between early PPV and initial intravitreal antibiotics alone despite high number of poor presenting VA of light-perception in early PPV group. Streptococcal infection and retinal detachment were major poor prognostic factors for vision.