Association of polymorphisms in the HTRA1 gene with myopia.

PURPOSE: To evaluate the associations of single-nucleotide polymorphisms (SNPs) in the high-temperature requirement protease A 1 (HTRA1) gene with myopia. METHODS: 25 SNPs in HTRA1 were selected, including 23 haplotype-tagging SNPs, SNP rs2142308 from a previous genome-wide association study (GWAS) of myopia and rs11200638, a SNP strongly associated with age-related macular degeneration (AMD). All SNPs were genotyped in a Hong Kong Chinese cohort of 533 myopia subjects (including 175 high myopia, 189 moderate myopia and 189 mild myopia) and 280 non-myopic controls. The association of individual SNPs were evaluated in overall myopia and different subgroups of myopia using logistic regression. RESULTS: A tagging SNP, rs11200647, was significantly associated with myopia (p=2.17×10-4, OR=0.67). Nominal associations were detected for the AMD-associated SNP rs11200638 (p=0.0042, OR=1.37) and tagging SNPs rs12266322 (p=0.0048, OR=0.59) and rs17103569 (p=0.047, OR=1.34). The association of rs11200647 with myopia remained significant after adjusting for rs11200638, rs12266322 and rs17103569. In sub-group analysis, two tagging SNPs, rs11200647 (p=2.24×10-4, OR=0.58) and rs12266322 (p=8.31×10-4, OR=0.39), showed significant association with moderate myopia. In haplotype association analysis, haplotypes AT (p=1.00×10-4, OR=1.77) and haplotype GT (p=0.0019, OR=0.64), defined by rs11200647 and rs66884382, were significantly associated with myopia. CONCLUSIONS: This study provided new evidence to support HTRA1 as an associated gene for myopia, especially moderate myopia. The findings suggested that myopia and AMD may have shared genetic components.

COMPLEX MACULAR HOLE CLOSURE BY TEMPORAL INTERNAL LIMITING MEMBRANE FLAP WITHOUT ENDOTAMPONADE.

PURPOSE: To evaluate the safety, efficacy, and imaging features of a novel surgical technique without endotamponade in repairing complex macular hole (MH). METHODS: Retrospective review of consecutive cases with complex MH underwent pars plana vitrectomy with temporal internal limiting membrane flap, which was stabilized using perfluorocarbon liquid and viscoelastics. At the conclusion of surgery, perfluorocarbon liquid was removed, and no endotamponade agent would be used. Complex MH was defined as a basal linear diameter of ≥400 µm and/or associated with high myopia. Visual acuity, pattern of MH closure on optical coherence tomography, formation of epiretinal membrane, and operative complications were reported. RESULTS: Twenty-four eyes were included, and the mean basal linear diameter was 988.3 µm. MH closure was achieved in 24 (100%), of which, 8 (33%) achieved type 1A closure. The mean postoperative logarithm of the minimum angle of resolution visual acuity improved from 0.93 at baseline to 0.74, 0.51, 0.55, and 0.52 at 1-month, 3-month, 6-month, and last follow-up, respectively. Foveal gliosis was observed in 3 eyes (12.5%), and 10 (41.7%) developed nasal epiretinal membrane. One eye developed vitreous hemorrhage, which resolved spontaneously. CONCLUSION: This novel surgical technique that requires no endotamponade is effective in achieving complex MH closure. A substantial proportion of patients developed epiretinal membrane, and its clinical significance requires further investigation.

Preoperative Intravitreal Conbercept Injection Reduced Both Angiogenic and Inflammatory Cytokines in Patients With Proliferative Diabetic Retinopathy.

Aims: To investigate the impact of intravitreal injection of conbercept, a recombinant fusion protein with decoy receptors for the vascular endothelial growth factor (VEGF) family, on intraocular concentrations of angiogenic and inflammatory mediators in patients with proliferative diabetic retinopathy (PDR), analyzed its potential impact on surgical outcomes. Methods: Forty eyes from 40 patients with PDR were included in this prospective study. Patients received intravitreal injection of conbercept followed by vitrectomy or phacovitrectomy in 1 week. Aqueous humor samples were collected before and 1 week after the conbercept injection. The concentrations of angiogenic and inflammatory cytokines and chemokines were measured by flow cytometry. Follow-up clinical data were collected and analyzed. Results: Intravitreal conbercept injection significantly decreased aqueous concentrations of VEGF (325.5 (baseline) versus 22.3 pg/mL (postinjection), p < 0.0001), PlGF (39.5 versus 24.5 pg/mL, p < 0.0001), and PDGF-A (54.1 versus 47.0 pg/mL, p = 0.0016), while no impact on bFGF levels. For inflammatory mediators, the concentration of TNF-α (0.79 versus 0.45 pg/mL, p = 0.0004) and IL-8 (180.6 versus 86 pg/mL, p < 0.0001) were decreased, while IL-6 (184.1 versus 333.7 pg/mL, p = 0.0003) and IL-10 (1.1 versus 1.5 pg/mL, p = 0.0032) were increased. No significant changes in IFN-γ or MCP-1 were detected. Three months after surgery, the mean best-corrected visual acuity improved from a baseline of 1.8 ± 0.1 logMAR to 0.7 ± 0.1 logMAR (p < 0.0001), with 36 eyes (90%) achieving an improvement of visual function. Conclusions: Intravitreal conbercept injection presents dual effects of antiangiogenesis and anti-inflammation and can be served as an adjuvant treatment to vitrectomy for PDR patients.

Associations of genetic variants for refractive error and axial length in adults with ocular endophenotypes in children: a cross-sectional and longitudinal study.

AIMS: To investigate the associations of genetic variants previously linked to axial length (AL) and spherical equivalent refraction (SE) in adults with refractive error and related endophenotypes in children, at baseline and 3-year follow-up. METHODS: 15 candidate single-nucleotide polymorphisms (SNPs), selected from previous Genome-Wide Association Studies and meta-analyses, were genotyped in 2819 Chinese children, who had undergone baseline and 3-year follow-up cycloplegic refraction, ocular biometry and ocular health examinations. Linear regression analyses were conducted to assess the associations of the SNPs with baseline measurements and longitudinal changes in SE, spherical power (SPH), AL, corneal radius of curvature (CR) and AL/CR ratio. RESULTS: SNPs ZMAT4 rs7829127, ZMAT4 rs16890057, TOX rs7837791, GRIA4 rs11601239 and RDH5 rs3138142 were associated with SE (ß=0.233, p=4.21×10-4; ß=0.221, p=7.87×10-4; ß=0.106, p=0.0076; ß=0.084, p=0.041; ß=0.14, p=0.013, respectively) and SPH (ß=0.24, p=2.3×10-4; ß=0.232, p=3.8×10-4; ß=0.088, p=0.025; ß=0.086, p=0.034; ß=0.14, p=0.012, respectively). Among them, ZMAT4 rs7829127 and rs16890057, were also associated with AL (ß=-0.128, p=5.6×10-4; ß=-0.128, p=5.21×10-4) and AL/CR ratio (ß=-0.014, p=0.0028; ß=-0.014, p=0.0034), whereas TOX rs7837791 was associated with AL (ß=-0.062, p=0.0058) and GRIA4 11 601 239 with AL/CR ratio (ß=-0.0058, p=0.049). Additionally, CD55 rs1652333 and RDH5 rs3138142 were associated with 3-year longitudinal changes in AL (ß=0.062, p=0.018; ß=-0.079, p=0.029) and CR (ß=0.014, p=0.027; ß=-0.018, p=0.035). CONCLUSION: Among SNPs previously associated with AL and SE in adults, variants in ZMAT4, TOX and GRIA4 were associated with AL, SE, SPH, and/or AL/CR ratio, while variants in RDH5 and CD55 showed associations with AL and CR changes in children.

Oxidative [4+2] Annulation of Pyrrole-2-carbaldehyde Derivatives with o-Hydroxyphenyl Propargylamines: Syntheses of 5,6,7-Trisubstituted Indolizines.

A base promoted oxidative [4+2] annulation of pyrrole-2-carbaldehyde derivatives with o-hydroxyphenyl propargylamines for the synthesis of highly substituted indolizines has been developed. Using DBN as base, a broad range of 5,6,7-trisubstituted indolizines have been prepared in good to excellent yields under mild conditions, and many useful functional groups can be tolerated.

Heritability and Genetic Factors of Astigmatism and Corneal Curvature: A Systematic Review and Meta-analysis.

PURPOSE: To systematically review and meta-analyze all reported heritability studies of refractive astigmatism (RA), corneal astigmatism (CA) and corneal curvature (CC), and evaluate the existing genetic associations of RA, CA and CC. DESIGN: Systematic review and meta-analysis (PROSPERO ID: CRD42023447370). METHODS: Studies that reported the heritability and genetic associations of RA, CA and/or CC were identified from PubMed, Web of Science and EMBASE (from inception to October 1, 2023). Newcastle-Ottawa Scale criteria was used to assess the risk of bias. Meta-analyses of heritability were conducted using random-effects model for mean difference. All current genetic associations were catalogued according to level of statistical significance. RESULTS: Pooled heritabilities were moderate for RA (h2 = 0.46, 95% CI: 0.27-0.65), CA (h2 = 0.48, 95% CI: 0.38-0.58) and CC (h2 = 0.64, 95% CI: 0.53-0.76). Subgroup analyses revealed significant differences between analysis methods (CA: P < .01; CC: P = .03) and populations (CA: P < .01; CC: P < .01) in both CA and CC, and between age groups in CA (P < .01). Totally 50 single-nucleotide polymorphisms (SNPs) in 10 genes have been reported with overlapping associations with RA, CA, and/or CC, with BMP3, FMNL2, HERC2, PROX1-AS1, and ZC3H11B associated with RA and CA, FBN1, NHSL1, and PDGFRA with CA and CC, TRAF3IP1 with RA and CC, and CASC15 with RA, CA, and CC. CONCLUSIONS: This study confirms moderate heritabilities of RA, CA and CC. Through evaluating overlapping SNPs or genes between these three phenotypes, we prioritized 50 SNPs in 10 genes as candidate variants for further validation. These findings highlight the complex genetic architecture of astigmatism and indicate shared and distinct genetic markers for different astigmatism-related corneal parameters. Future studies in different populations and functional studies evaluating the roles of the involved genes in astigmatism are warranted.

Integrated image-based deep learning and language models for primary diabetes care.

Primary diabetes care and diabetic retinopathy (DR) screening persist as major public health challenges due to a shortage of trained primary care physicians (PCPs), particularly in low-resource settings. Here, to bridge the gaps, we developed an integrated image-language system (DeepDR-LLM), combining a large language model (LLM module) and image-based deep learning (DeepDR-Transformer), to provide individualized diabetes management recommendations to PCPs. In a retrospective evaluation, the LLM module demonstrated comparable performance to PCPs and endocrinology residents when tested in English and outperformed PCPs and had comparable performance to endocrinology residents in Chinese. For identifying referable DR, the average PCP's accuracy was 81.0% unassisted and 92.3% assisted by DeepDR-Transformer. Furthermore, we performed a single-center real-world prospective study, deploying DeepDR-LLM. We compared diabetes management adherence of patients under the unassisted PCP arm (n = 397) with those under the PCP+DeepDR-LLM arm (n = 372). Patients with newly diagnosed diabetes in the PCP+DeepDR-LLM arm showed better self-management behaviors throughout follow-up (P < 0.05). For patients with referral DR, those in the PCP+DeepDR-LLM arm were more likely to adhere to DR referrals (P < 0.01). Additionally, DeepDR-LLM deployment improved the quality and empathy level of management recommendations. Given its multifaceted performance, DeepDR-LLM holds promise as a digital solution for enhancing primary diabetes care and DR screening.

Etiology including epigenetic defects of retinoblastoma.

Retinoblastoma (RB), originating from the developing retina, is an aggressive intraocular malignant neoplasm in childhood. Biallelic loss of RB1 is conventionally considered a prerequisite for initiating RB development in most RB cases. Additional genetic mutations arising from genome instability following RB1 mutations are proposed to be required to promote RB development. Recent advancements in high throughput sequencing technologies allow a deeper and more comprehensive understanding of the etiology of RB that additional genetic alterations following RB1 biallelic loss are rare, yet epigenetic changes driven by RB1 loss emerge as a critical contributor promoting RB tumorigenesis. Multiple epigenetic regulators have been found to be dysregulated and to contribute to RB development, including noncoding RNAs, DNA methylations, RNA modifications, chromatin conformations, and histone modifications. A full understanding of the roles of genetic and epigenetic alterations in RB formation is crucial in facilitating the translation of these findings into effective treatment strategies for RB. In this review, we summarize current knowledge concerning genetic defects and epigenetic dysregulations in RB, aiming to help understand their links and roles in RB tumorigenesis.

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

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

Advances in myopia control strategies for children.

Myopia has long been a global threat to public health. Timely interventions are likely to reduce the risk of vision-threatening complications. There are both established and rapidly evolving therapeutic approaches to slow myopia progression and/or delay its onset. The effective methods for slowing myopia progression include atropine eye-drops, defocus incorporated multiple segments (DIMS) spectacle lenses, spectacle lenses with highly aspherical lenslets target (HALT), diffusion optics technology (DOT) spectacle lenses, red light therapy (RLT), multifocal soft contact lenses and orthokeratology. Among these, 0.05% atropine, HALT lenses, RLT and +3.00 peripheral addition soft contact lenses yield over 60% reduction in myopia progression, whereas DIMS, DOT and MiSight contact lenses demonstrate at least 50% myopia control efficacy. 0.05% atropine demonstrates a more optimal balance of efficacy and safety than 0.01%. The efficacy of 0.01% atropine has not been consistent and requires further validation across diverse ethnicities. Combining atropine 0.01% with orthokeratology or DIMS spectacles yields better outcomes than using these interventions as monotherapies. Increased outdoor time is an effective public health strategy for myopia prevention while recent studies suggest that 0.05% low-concentration atropine and RLT therapy have promising potential as clinical myopia prevention interventions for high-risk groups. Myopia control spectacle lenses, being the least invasive, are safe for long-term use. However, when considering other approaches, it is essential to ensure proper instruction and regular follow-ups to maintain safety and monitor any potential complications. Ultimately, significant advances have been made in myopia control strategies, many of which have shown meaningful clinical outcomes. However, regular use and adequate safety monitoring over extended durations are imperative to foster confidence that can only come from extensive clinical experience.

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.

Genetic Associations of Primary Angle-Closure Disease: A Systematic Review and Meta-Analysis.

Importance: Effects of genetic variants on primary angle-closure disease remained uncertain. Objective: To systematically review the associations of common single-nucleotide variants (SNVs) and rare coding variants with primary angle-closure disease, its subtypes (including primary angle-closure glaucoma, primary angle-closure suspect, and primary angle-closure) and progression. Data Sources: Eligible studies from PubMed, Embase, and Web of Science were retrieved up to April 3, 2023. SNV information was extracted from eligible reports and 2 genome-wide association studies summary statistics, UK BioBank and FinnGen. Study Selection: Studies providing analyzable genotype or allele data in a case-control design for primary angle-closure disease association and longitudinal case-only design for primary angle-closure disease progression. Data Extraction and Synthesis: PRISMA guidelines were used for literature screening and the Newcastle Ottawa Scale for data quality assessment. Pooled effect size with 95% CIs of SNV associations were calculated using fixed- or random-effect models according to I2 statistics. Main Outcomes and Measures: SNVs reported in 2 or more studies were meta-analyzed to generate pooled odds ratios and P values. Common and rare coding variants from single reports were summarized. Results: Sixty-nine citations were eligible for meta-analysis on overall primary angle-closure disease, involving 206 SNVs in 64 genes or loci. Seventeen SNVs in 15 genes or loci showed associations with primary angle-closure disease, and 15 SNVs in 13 genes or loci showed associations with primary angle-closure glaucoma. Two SNVs, ABCA1 rs2422493 and ZNRF3 rs3178915, were associated only with primary angle-closure disease. Two SNVs, PCMTD1-ST18 rs1015213 and COL11A1 rs3753841, were associated with primary angle-closure suspect, and 1 SNV, MMP9 rs3918249, was associated with primary angle-closure. This systematic review and meta-analysis newly confirmed 7 genes or loci associated with primary angle-closure glaucoma: ATOH7, CALCRL, FBN1, IL6, LOXL1, MMP19, and VAV3. Common and rare coding variants in 16 genes or loci that have been associated with primary angle-closure disease were cataloged. Stratification analysis revealed different primary angle-closure disease-associated genes in different ethnic populations. Only 1 study regarding the genetic association of primary angle-closure glaucoma progression was identified. Conclusions and Relevance: This study revealed the genetic complexity of primary angle-closure disease, involving common SNVs and rare coding variants in more than 30 genes or loci, with ethnic and phenotypic diversities. Further replication, genotype-phenotype correlation, and pathway analyses are warranted.

Five-Year Clinical Trial of the Low-Concentration Atropine for Myopia Progression (LAMP) Study: Phase 4 Report.

PURPOSE: To evaluate (1) the long-term efficacy of low-concentration atropine over 5 years, (2) the proportion of children requiring re-treatment and associated factors, and (3) the efficacy of pro re nata (PRN) re-treatment using 0.05% atropine from years 3 to 5. DESIGN: Randomized, double-masked extended trial. PARTICIPANTS: Children 4 to 12 years of age originally from the Low-Concentration Atropine for Myopia Progression (LAMP) study. METHODS: Children 4 to 12 years of age originally from the LAMP study were followed up for 5 years. During the third year, children in each group originally receiving 0.05%, 0.025%, and 0.01% atropine were randomized to continued treatment and treatment cessation. During years 4 and 5, all continued treatment subgroups were switched to 0.05% atropine for continued treatment, whereas all treatment cessation subgroups followed a PRN re-treatment protocol to resume 0.05% atropine for children with myopic progressions of 0.5 diopter (D) or more over 1 year. Generalized estimating equations were used to compare the changes in spherical equivalent (SE) progression and axial length (AL) elongation among groups. MAIN OUTCOMES MEASURES: (1) Changes in SE and AL in different groups over 5 years, (2) the proportion of children who needed re-treatment, and (3) changes in SE and AL in the continued treatment and PRN re-treatment groups from years 3 to 5. RESULTS: Two hundred seventy (82.8%) of 326 children (82.5%) from the third year completed 5 years of follow-up. Over 5 years, the cumulative mean SE progressions were -1.34 ± 1.40 D, -1.97 ± 1.03 D, and -2.34 ± 1.71 D for the continued treatment groups with initial 0.05%, 0.025%, and 0.01% atropine, respectively (P = 0.02). Similar trends were observed in AL elongation (P = 0.01). Among the PRN re-treatment group, 87.9% of children (94/107) needed re-treatment. The proportion of re-treatment across all studied concentrations was similar (P = 0.76). The SE progressions for continued treatment and PRN re-treatment groups from years 3 to 5 were -0.97 ± 0.82 D and -1.00 ± 0.74 D (P = 0.55) and the AL elongations were 0.51 ± 0.34 mm and 0.49 ± 0.32 mm (P = 0.84), respectively. CONCLUSIONS: Over 5 years, the continued 0.05% atropine treatment demonstrated good efficacy for myopia control. Most children needed to restart treatment after atropine cessation at year 3. Restarted treatment with 0.05% atropine achieved similar efficacy as continued treatment. Children should be considered for re-treatment if myopia progresses after treatment cessation. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

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.

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.

Light exposure therapy for myopia control: a systematic review and Bayesian network meta-analysis.

AIMS: To compare and rank the myopia control effects of different light wavelengths in children using a systematic review and Bayesian network meta-analysis (Bayesian NMA). METHODS: The review protocol was registered with PROSPERO. We searched PubMed, EMBASE and MEDLINE for relevant clinical and animal studies published as of 2 February 2023. We included studies comparing red, violet or full-spectrum light with controls. Data extracted included descriptive statistics and study outcomes (axial length (AL) elongation and progression of spherical equivalent (SE) refraction). After quality assessment, estimates of treatment effect outcomes (mean differences (MDs) and 95% CIs) were first pooled for the animal and clinical studies in a traditional meta-analysis. To compare and rank the different light wavelengths, the Bayesian NMA was then conducted for all the included clinical studies (12 studies) and separately for only randomised controlled trials (8 studies). MDs, 95% credible intervals (CrIs) and ranks of the various light wavelengths were estimated in the Bayesian NMA. RESULTS: When all clinical studies were included in the Bayesian NMA (12 studies), only red-light significantly slowed AL elongation, MD (95% CrI), -0.38 mm (-0.59 mm to -0.16 mm)/year and SE refraction progression, 0.72D (0.35D to 1.10D)/year compared with controls. It remained the only significant intervention when effect sizes from only RCTs (eight studies) were separately combined, (-0.28 mm (-0.40 mm to -0.15 mm)/year and 0.57D (0.22D to 0.92D)/year, for AL and SE refraction, respectively). CONCLUSION: Myopia control efficacy varied among different wavelengths of light, with red light ranked as the most effective. PROSPERO REGISTRATION NUMBER: Clinical studies: CRD42022368998; animal studies: CRD42022368671.

Effects of firsthand tobacco smoking on retinal vessel caliber: a systematic review and meta-analysis.

PURPOSE: To review the effects of firsthand tobacco smoking on central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) of firsthand tobacco smokers. METHODS: We performed a search on EMBASE and PubMed for studies up to 15th July 2022. Two independent reviewers selected studies with baseline data of CRAE and CRVE of current smokers, nonsmokers, and former smokers. Initial search identified 893 studies, of which 10 were included in the meta-analysis. Two independent reviewers extracted data from the included studies. The quality of studies was assessed by the Newcastle-Ottawa Scale. RESULTS: In this meta-analysis, 7431 nonsmokers, 2448 current smokers and 5786 former smokers, as well as 7404 nonsmokers, 2430 current smokers and 5763 former smokers were included in CRAE and CRVE analysis respectively. Nonsmokers had narrower CRVE (Weighted mean difference [WMD], -12.15; 95% CI, -17.33 - -6.96) and CRAE (WMD, -4.77; 95% CI, -7.96 - -1.57) than current smokers, and narrower CRVE (WMD, -3.08; 95% CI, -6.06 - -0.11) than former smokers. Current smokers had wider CRVE (WMD, 10.42; 95% CI, 7.80 - 13.04) and CRAE (WMD, 7.05; 95% CI, 6.65 - 7.46) than former smokers. Subgroup analysis and sensitivity analysis were performed. CONCLUSION: Firsthand tobacco smoking resulted in wider CRAE and CRVE in current and former smokers, particularly in CRVE, and such changes may not be reversible after smoking cessation. Therefore, retinal vessel caliber may reflect the effects of firsthand tobacco smoking and be used to estimate the risk of cardiovascular diseases.

Systemic Involvement in Immunoglobulin G4-Related Ophthalmic Disease.

BACKGROUND: Immunoglobulin G4-related ophthalmic disease (IgG4-ROD) poses clinical challenges due to its heterogeneous ocular and systemic manifestations. We aim to report the systemic involvement and the clinical, serological and radiological associations of a cohort of Chinese patients. METHODS: A territory-wide, biopsy-proven, Chinese cohort. A retrospective, masked chart review of medical records, orbital images, and histopathology reports. RESULTS: A total of 122 (65 male) patients with a follow-up of 81 ± 49 (24 to 84) months were reviewed. Ninety (74%) patients presented bilaterally. Subacute upper eyelid swelling was the commonest presentation (82/122, 67%). During follow-up, 91/122 patients (75%) underwent extra-orbital imaging including computer tomography (692 films), ultrasonography (182 films), magnetic resonance imaging (76 films) and whole body FDG-PET scan (33 films). Eighty-six (95%) of these 91 patients had extra-orbital involvement radiologically (2.7 ± 1.6 regions, range: 0 to 9). Lymph node was the most prevalent (N = 60,66%), followed by salivary gland (N = 51,56%), lung (N = 49,54%), kidney (N = 22, 24%), hepatobiliary tree (N = 18, 20%) and pancreas (N = 17, 19%). Other organs include thyroid, aorta, meninges/brain and skin. Twenty-eight (23%) patients had allergic diseases (19 asthma, 16 allergic rhinitis, and 6 eczemas). Fifty-seven (48%) patients had paranasal sinusitis. Serum eosinophilia was associated with a higher number (3.24 versus 2.52, P = 0.0304) of organ involvement. Patients with deep organ involvement was associated with a higher age of IgG4-ROD onset (70 ± 12 versus 56 ± 13, P < 0.0001). CONCLUSIONS: 95% of the patients who underwent systemic imaging in our cohort had systemic organ involvement. An early physicians' assessment and radiological imaging are recommended after the diagnosis of IgG4-ROD.