Association of sodium-glucose cotransporter-2 inhibitors and the risk of retinal vascular occlusion: A real-world retrospective cohort study in Taiwan.

AIMS: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are proposed to alleviate the development of inflammatory eye diseases. However, the association between SGLT2i and retinal vascular occlusion remains unclear. Therefore, this study aims to explore the effects of SGLT2i on the incidence of retinal vascular occlusion. MATERIALS AND METHODS: This retrospective cohort study analysed electronic medical records data from the largest multi-institutional database in Taiwan. Individuals who initiated SGLT2is and dipeptidyl peptidase 4 inhibitors (DPP4is) between 2016 and 2019 were included in our analysis. To conduct a homogenous comparison, inverse probability of treatment weighting with propensity scoring was employed. The primary outcome was retinal vascular occlusion, and the secondary outcomes were retinal vascular occlusion-related complications (macular oedema, vitreous haemorrhage, and tractional retinal detachment) and conditions requiring vitreoretinal intervention (intravitreal injection, retinal laser therapy, and vitrectomy). RESULTS: In total, 12,074 SGLT2i users and 39,318 DPP4i users were included. The incidence rate of retinal vascular occlusion in the SGLT2i and DPP4i groups was 1.2 (95% confidence interval [CI], 0.9-1.4) and 1.6 (95% CI, 1.3-1.8) events per 1000 person-years, respectively, which yielded a subdistribution hazard ratio (SHR) of 0.74 (95% CI, 0.55-0.99). Similar risk reductions were observed in the retinal vascular occlusion-related complications (SHR, 0.76; 95% CI, 0.69-0.84) and conditions requiring vitreoretinal intervention (SHR, 0.84; 95% CI, 0.77-0.94). CONCLUSIONS: In this multi-institutional study in Taiwan, SGLT2i use was associated with a reduced risk of retinal vascular occlusion. Further prospective studies are required to ascertain this association.

A comparative study of stereopsis in term and preterm children with and without retinopathy of prematurity.

PURPOSE: To evaluate stereopsis in term-born, preterm, and preterm children with and without retinopathy of prematurity (ROP) and its treatment. METHODS: The cross-sectional study included 322 children between 3 and 11 years of age born term or preterm, with or without ROP, and with or without treatment for ROP. The ROP treatments were laser therapy, intravitreal injection (IVI) of anti-vascular endothelial growth factor, or their combination. Stereoacuity was measured using the Titmus Stereo Test, and the results among various age groups were analyzed. RESULTS: Stereopsis was found to improve with increasing age at testing (P < 0.001) across the entire study population. The term group exhibited significantly better stereoacuity than the preterm group (P < 0.001). At 3-5 years and 6-8 years, the preterm children without ROP exhibited significantly better stereoacuity than did those with ROP (P < 0.001 and P = 0.02, respectively); however, at 9-11 years, both groups exhibited similar stereoacuity (P = 0.34). The stereoacuity in the children with untreated ROP was similar to that of the children with treated ROP in all age groups (P > 0.05). No significant differences in stereopsis were identified between children with ROP treated with laser versus with IVI (P > 0.05). From multivariate analysis, younger age at testing (P = 0.001) and younger gestational age (P < 0.001) were associated with poorer stereopsis. CONCLUSIONS: Stereopsis development gradually improved with age in all groups. The children born preterm exhibited poorer stereoacuity than those born term. Children with ROP treated with laser photocoagulation versus IVI may exhibit similar levels of stereoacuity. Younger age at testing and gestational age were independent risk factors for poorer stereoacuity.

LONGITUDINAL CHANGES IN CHOROIDAL THICKNESS IN CHILDREN WITH A HISTORY OF PREMATURITY: An 18-Month Prospective Cohort Study.

PURPOSE: To evaluate choroidal changes over time in school-age children with a history of prematurity. METHODS: A study of 416 eyes of 208 eligible participants, including 88, 190, 36, 56, and 46 eyes in the full-term control, preterm, spontaneously regressed retinopathy of prematurity, intravitreal bevacizumab (injection of bevacizumab)-treated retinopathy of prematurity, and laser-treated retinopathy of prematurity groups, respectively, were enrolled in this study. The choroidal thickness was measured 4 times at 6-month intervals using optical coherence tomography. RESULTS: Of all the groups, the laser-treated children had the thinnest choroid compared with full-term children (-52.3 µ m, P = 0.04). Preterm children exhibited greater attenuation in choroidal thickness over time than did full-term children (-6.3 ± 26.9 and -1.1 ± 12.8 µ m/year, P = 0.03), whereas no difference was observed between injection of bevacizumab and laser treatments (-4.6 ± 18.9 and -2.0 ± 15.7 µ m/year, P = 0.46). In all groups, the changes in axial length were negatively associated with the changes in choroidal thickness (all P < 0.05). CONCLUSION: A greater attenuation in choroid thickness over time was observed in preterm children than in full-term children, but this attenuation did not differ between injection of bevacizumab and laser treatments. Axial elongation was associated with choroidal thinning in school-age children.

Exploring the Location of Corneal Pigmented Arc and Myopia Control Efficacy in Orthokeratology-Treated Children Using Pentacam Measurements.

OBJECTIVES: To determine the location and intensity of the corneal pigmented arc in orthokeratology (ortho-k)-treated children and its relationship with annual axial length (AL) change using Pentacam. METHODS: This retrospective cohort study enrolled children aged 9 to 15 years who had been followed up for at least one year after ortho-k treatment for myopia control. A Pentacam was used to determine the location and intensity of pigmented arc after lens wear. Annual AL changes were further used as the outcome measurement to determine their relationships with the location and intensity of pigmented arc using generalized estimating equations (GEE). RESULTS: In total, 62 eyes from 33 patients (mean age 10.9 years) were included in our final analysis. The mean follow-up time was 30.6 months. The mean annual AL changes were 0.10 mm. Age statistically correlated with annual AL change (GEE, P= 0.033). In addition, the annual AL change was negatively associated with the relative vertical distance of the lowest density of pigmented arc point based on the visual center, pupil center, and corneal thinnest point after adjustment with age ( P =0.005, P =0.004, and P< 0.001, respectively). CONCLUSIONS: Pentacam could be a useful tool for evaluating the location and intensity of the corneal pigmented arc. In addition, there was a negative correlation between the vertical distance of the pigmented arc and annual AL change. These findings may provide important information regarding myopia control, next-generation ortho-k design, and prescription.

Taiwan ocular inflammation society consensus recommendations for the management of juvenile idiopathic arthritis-associated uveitis.

We presented the development of a consensus guideline for managing juvenile idiopathic arthritis-associated uveitis (JIAU) in Taiwan, considering regional differences in manifestation and epidemiology. The Taiwan Ocular Inflammation Society (TOIS) committee formulated this guideline using a modified Delphi approach with two panel meetings. Recommendations were based on a comprehensive evidence-based literature review and expert clinical experiences, and were graded according to the Oxford Centre for Evidence-Based Medicine's "Levels of Evidence" guideline (March 2009). The TOIS consensus guideline consists of 10 recommendations in four categories: screening and diagnosis, treatment, complications, and monitoring, covering a total of 27 items. These recommendations received over 75% agreement from the panelists. Early diagnosis and a coordinated referral system between ophthalmologists and pediatric rheumatologists are crucial to prevent irreversible visual impairment in children with JIAU. However, achieving a balance between disease activity and medication use remains a key challenge in JIAU management, necessitating further clinical studies.

MicroRNA-152-3p and MicroRNA-196a-5p Are Downregulated When Müller Cells Are Promoted by Components of the Internal Limiting Membrane: Implications for Macular Hole Healing.

Müller cells play a critical role in the closure of macular holes, and their proliferation and migration are facilitated by the internal limiting membrane (ILM). Despite the importance of this process, the underlying molecular mechanism remains underexplored. This study investigated the effects of ILM components on the microRNA (miRNA) profile of Müller cells. Rat Müller cells (rMC-1) were cultured with a culture insert and varying concentrations of ILM component coatings, namely, collagen IV, laminin, and fibronectin, and cell migration was assessed by measuring cell-free areas in successive photographs following insert removal. MiRNAs were then extracted from these cells and analyzed. Mimics and inhibitors of miRNA candidates were transfected into Müller cells, and a cell migration assay and additional cell viability assays were performed. The results revealed that the ILM components promoted Müller cell migration (p < 0.01). Among the miRNA candidates, miR-194-3p was upregulated, whereas miR-125b-1-3p, miR-132-3p, miR-146b-5p, miR-152-3p, miR-196a-5p, miR-542-5p, miR-871-3p, miR-1839-5p, and miR-3573-3p were significantly downregulated (p < 0.05; fold change > 1.5). Moreover, miR-152-3p and miR-196a-5p reduced cell migration (p < 0.05) and proliferation (p < 0.001), and their suppressive effects were reversed by their respective inhibitors. In conclusion, miRNAs were regulated in ILM component-activated Müller cells, with miR-152-3p and miR-196a-5p regulating Müller cell migration and proliferation. These results serve as a basis for understanding the molecular healing process of macular holes and identifying potential new target genes in future research.

A Surgical Approach for Managing Refractory Macular Holes Using the Human Amniotic Membrane Patch Technique.

To introduce a novel surgical technique using the human amniotic membrane (hAM) patch technique to address refractory macular holes (MHs). After vitrectomy, the hAM patch was positioned on top of the MH with the chorion side facing downward. Viscoat (Alcon Laboratories) was applied on top of the hAM patch for better fixation. Fluid-air exchange was then performed and 20% SF6 or 10% C3F8 tamponade was administered after the surgery. Five patients with refractory MHs larger than 400 µm underwent the hAM patch technique. After a minimum 2-year follow-up, results showed 100% closure of MHs, 80% improvement in visual acuity, and a notable enhancement in best-corrected logMAR visual acuity from 0.98 to 0.72 (P = 0.039). Dislocation of hAM patch occurred among 3 out of 5 patients (60%). The hAM patch technique appears to be a promising approach for addressing refractory MHs. [Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.].

Trocar blade-assisted skewer technique for phacoemulsification of a dislocated lens.

A posteriorly dislocated lens is often managed with a fragmatome through a pars plana approach because it is difficult to manage anteriorly. The lens often sinks to the surface of the retina or floats around in the vitreous cavity during pars plana lensectomy. Mechanical trauma can occur while removing the dislocated lens fragments. However, sometimes the lens can be confined to the anterior vitreous cavity even though the zonules are completely disrupted. It would be ideal if there was a simple way to stabilize and support the lens so that the lens could remain in the posterior chamber while phacoemulsification is performed through a corneal incision as usual. We describe a technique using a trocar blade to stabilize the lens while performing phacoemulsification through a corneal incision. We found it to be a useful and safe instrument to support the subluxated lens during phacoemulsification.

Increased late-onset glaucoma risk following vitrectomy for macular pucker or hole.

OBJECTIVES: The long-term risk of developing glaucoma after vitrectomy remains uncertain. This retrospective population-based cohort study aimed to explore this risk following vitrectomy for macular pucker or hole. METHODS: Utilizing Taiwan's National Health Insurance Research Database (NHIRD), we included patients who were older than 18 years and had undergone vitrectomy surgery between 2011 and 2019. Exclusions were made for patients with prior diagnoses of glaucoma, congenital or secondary glaucoma, as well as those who had received previous vitreoretinal treatments or had undergone multiple vitrectomies. RESULTS: After an average follow-up period of 51 and 53 months respectively for the vitrectomized and non-vitrectomized group, our results showed a relative risk of 1.71 for glaucoma development in the vitrectomized group. Higher adjusted hazard ratios were also observed for open-angle glaucoma and normal tension glaucoma. Increased risks were associated with male sex, obstructive sleep apnoea, and migraine. In the subgroup analysis, phakic eyes at baseline and those who had undergone cataract surgery post-vitrectomy were associated with a lower risk of glaucoma development during follow-up. Among all glaucoma events, pseudophakic status at baseline had the shortest interval to glaucoma development following vitrectomy. CONCLUSIONS: These findings underscore the potential relationship between vitrectomy and glaucoma onset, emphasizing the need for vigilant monitoring and early detection of glaucoma in post-vitrectomy patients.

Association Between Pentoxifylline Use and Diabetic Retinopathy in Patients with Type 2 Diabetes Mellitus and Chronic Kidney Disease: A Multi-Institutional Cohort Study.

BACKGROUND: Pentoxifylline is administrated to improve the hemodynamics of patients with chronic kidney disease (CKD). Despite the improvement of capillary blood flow velocity in retina after pentoxifylline use, no evidence has been provided to prove the protective effect for diabetic retinopathy (DR). Therefore, this study aimed to assess the risk of DR in pentoxifylline users with CKD and diabetes mellitus (DM). MATERIAL AND METHODS: In this retrospective cohort study, Chang Gung Research Database, which includes the data of patients with CKD and DM from 2003 to 2019, was used. Each calendar year was divided into 4 data units with 3 months each for every patient and every year during the follow-up. The ocular outcomes were new-onset DR, DR-related complications, and vitreoretinal interventions. RESULTS: Total 56,439 patients without preexisting DR and 5,039 patients with preexisting DR were included in this study. Exposure to pentoxifylline was associated with elevated risk of new-onset DR (adjusted hazard ratio = 1.24, 95% confidence interval = 1.13-1.36) in patients without preexisting DR. Additionally, exposure to pentoxifylline was associated with elevated risk of DR-related complications and vitreoretinal interventions in patients with or without preexisting DR. CONCLUSIONS: Exposure to pentoxifylline is associated with elevated risk of DR, regardless of whether patients have preexisting DR.

Noncontact optical device for measuring blood glucose in aqueous humor: a pilot clinical study investigating correlation with blood glucose levels.

Significance: Monitoring blood glucose levels is crucial for individuals with diabetes. Noninvasive methods for measuring serum glucose levels have been explored to aid in blood glucose control for diabetes management. Aim: We introduced a noncontact optical glucometer (NCGM) for measuring glucose levels in the aqueous humor of the human eye. We also investigated the correlation between glucose levels in the NCGM and the aqueous humor, blood samples, and self-monitoring blood glucose devices. Approach: The optical system used in this study measured both the near-infrared absorption and polarized rotatory distribution of glucose molecules in the human aqueous humor. This prospective study's outcomes were eye aqueous glucose level, preoperative blood glucose level, intraoperative blood glucose level, and NCGM reading of patients in a single center in Taiwan. Results: The NCGM's measurements showed a strong correlation with blood glucose levels (intra-class correlation [ICC]: 0.95 to 0.98) and aqueous humor glucose levels (ICC: 0.76), indicating its ability to noninvasively measure blood glucose levels in human subjects. Conclusions: This NCGM may offer a convenient, pain-free, and rapid tool for measuring blood glucose levels in diabetic patients. The device could represent a significant advancement in noncontact hybrid optical glucose measurement systems.

Diagnosis and treatment of syphilitic uveitis: Taiwan experts consensus.

A recent resurgence in the incidence of syphilis has sparked a new interest in this old disease. Syphilitic uveitis remains a challenging disease, among the variable syphilis infections, due to the diagnostic complexity and the wide clinical manifestations. Here, we provide recommendations regarding clinical manifestations, diagnosis, and treatment for patients with syphilitic uveitis in Taiwan based on an expert meeting and consensus from experienced uveitis specialists.

Use of corticosteroids in non-infectious uveitis - expert consensus in Taiwan.

PURPOSE: To offer consensus on the utilization of corticosteroids (CS) for treating non-infectious uveitis in the context of clinical practice in Taiwan. This entails examining the different administration methods, their advantages and disadvantages, and considering alternative treatments according to the prevailing evidence and health policies. METHODS: Ten ophthalmologists and one rheumatologist convened on December 11, 2022, to review and discuss literature on the topic. The databases explored were the Central Cochrane library, EMBASE, Medline, PUBMED, and Web of Science using relevant keywords. The search spanned from January 1996 to June 2023. After the initial results of the literature review were presented, open voting determined the final statements, with a statement being accepted if it secured more than 70% agreement. This consensus was then presented at significant meetings for further discussions before the final version was established. RESULTS: A flow chart and nine statements emerged from the deliberations. They address the importance of CS in uveitis management, guidelines for using topical CS, indications for both periocular or intravitreal and systemic therapies, and tapering and discontinuation methods for both topical and systemic CS. CONCLUSION: While CS are a cornerstone for non-infectious uveitis treatment, their administration requires careful consideration, depending on the clinical situation and the specific type of uveitis. The consensus generated from this article provides a guideline for practitioners in Taiwan, taking into account local health policies and the latest research on the subject. It emphasizes the significance of strategic tapering, the potential for alternative therapies, and the importance of patient-centric care.

Systemic effects of anti-VEGF intravitreal injection in patients with age-related macular degeneration: A multi-institutional real-world study.

PURPOSE: In individuals aged >50 years, age-related macular degeneration (AMD) is the leading cause of irreversible blindness. Intravitreal injections of antivascular endothelial growth factor (VEGF) agents (bevacizumab, ranibizumab, and aflibercept) show good efficacy and similar incidences of systemic adverse events (SAEs). However, comparative studies between agents are limited. Our study aimed to compare the real-world SAE risks of bevacizumab, ranibizumab, and aflibercept users. METHODS: This retrospective cohort study identified new bevacizumab, ranibizumab, and aflibercept users in a multi-institutional database in Taiwan between 2014 and 2019. Inverse probability of treatment weights (IPTW) with propensity scores was conducted to achieve homogeneity among groups. The Fine and Gray model was utilized to estimate the subdistribution hazard ratio and 95% confidence interval. RESULTS: This study included 701 bevacizumab, 463 ranibizumab, and 984 aflibercept users. After IPTW, all covariates were well-balanced. All three anti-VEGF agents had a low and comparable number per 100 person-years of major adverse cardiac events, heart failure, thromboembolic events, major bleeding, all-cause admission, and all-cause death (all P > 0.05). No significant differences in long-term change of systolic and diastolic blood pressure, low-density lipoprotein, estimated glomerular filtration rate, and alanine transaminase (all P for interaction > 0.05) were observed among groups. CONCLUSION: Bevacizumab, ranibizumab, and aflibercept had a good systemic safety profile in this study. All groups showed a low and similar SAE risk and no differences in their long-term change of laboratory data. Therefore, these anti-VEGF agents could be prescribed safely to patients with AMD.

Corneal Endothelial Morphology and Ocular Biometric Indexes in Premature Children With and Without Retinopathy of Prematurity.

Purpose: The purpose of this study was to analyze human corneal endothelial cells (HCECs) morphology and ocular biometrics in premature (PM) children with or without retinopathy of prematurity (ROP). Methods: Retrospective data on patient demographics, HCECs status, and ocular biometrics with at least 2 visits between 2016 and 2021 were reviewed. The main outcomes were endothelial cell density (ECD), coefficient of variation (CV), hexagonal cell ratio (HEX), central corneal thickness (CCT), axial length, anterior chamber depth, keratometry, corneal diameter, pupil diameter, and refraction status. Generalized estimating equation was used to evaluate the differences between PM no-ROP and ROP groups. We also analyzed the trend of ECD, CV, HEX, and CCT change with age between groups. Results: The study included 173 PM patients without ROP and 139 patients with ROP. A total of 666 and 544 measurements were recorded in the PM no-ROP and ROP groups, respectively. The ROP group had higher spherical power, myopic spherical equivalent (SE), and steeper steep keratometry (K; P < 0.05). The ROP group had higher CV (P = 0.0144), lower HEX (P = 0.0012) and thicker CCT (P = 0.0035). In the HCECs parameters, the ROP group had slower ECD decrement (P < 0.0001), faster CV decrement (P = 0.0060), and faster HEX increment (P = 0.0001). A difference in corneal morphology changes between the ROP and PM no-ROP groups were prominent in patients with lower gestational age (GA) in the subgroup analysis. Conclusions: Worse HCECs morphology and higher myopic status were initially observed in patients with prior ROP but not in PM patients with no-ROP. ECD and HCECs morphology improved with age, especially in patients with low GA.

Cross-sectional Analysis of Outer Retinal Tubulation in Inherited Retinal Diseases: A Multicenter Study.

PURPOSE: This study aims to explore genetic variants that potentially lead to outer retinal tubulation (ORT), estimate the prevalence of ORT in these candidate genes, and investigate the clinical etiology of ORT in patients with inherited retinal diseases (IRDs), with respect to each gene. DESIGN: Retrospective cohort study. METHODS: A retrospective cross-sectional review was conducted on 565 patients with molecular diagnoses of IRD, confirming the presence of ORT as noted in each patient's respective spectral-domain optical coherence tomography (SD-OCT) imaging. Using SD-OCT imaging, the presence of ORT was analyzed in relation to specific genetic variants and phenotypic characteristics. Outcomes included the observed ORT frequencies across two gene-specific cohorts: non- retinal pigment epithelium (RPE)-specific genes, and RPE-specific genes; and to investigate the analogous characteristics caused by variants in these genes. RESULTS: Among the 565 patients included in this study, 104 exhibited ORT on SD-OCT. We observed ORT frequencies among the following genes from our patient cohort: 100% (23/23) forCHM, 100%(2/2) forPNPLA6, 100% (4/4) forRCBTB1, 100% formtDNA[100% (4/4) forMT-TL1and 100% (1/1) formtDNAdeletion], 100% (1/1) forOAT, 95.2% (20/21) forCYP4V2, 72.7% (8/11) forCHMfemale carriers, 66.7% (2/3) forC1QTNF5, 57.1% (8/14) forPROM1, 53.8% (7/13) forPRPH2, 42.9% (3/7) forCERKL, 28.6% (2/7) forCDHR1, 20% (1/5) forRPE65, 4% (18/445) forABCA4.In contrast, ORT was not observed in any patients with photoreceptor-specific gene variants, such asRHO(n=13),USH2A(n=118),EYS(n=70),PDE6B(n=10),PDE6A(n=4),and others. CONCLUSION: These results illustrate a compelling association between the presence of ORT and IRDs caused by variants in RPE-specific genes, as well as non-RPE-specific genes. In contrast, IRDs caused by photoreceptor-specific genes are typically not associated with ORT occurrence. Further analysis revealed that ORT tends to manifest in IRDs with milder intraretinal pigment migration (IPM), a finding that is typically associated with RPE-specific genes. These findings regarding ORT, genetic factors, atrophic patterns in the fundus, and IPM provide valuable insight into the complex etiology of IRDs. Future prospective studies are needed to further explore the association and underlying mechanisms of ORT in these contexts.

Association of serum levels of inflammatory cytokines with retinopathy of prematurity in preterm infants.

Introduction: Retinopathy of prematurity (ROP) is a retinal vascular developmental disease associated with risks factors such as supplementary oxygen use or low birth weight/early gestational age. Multiple studies have reported associations between ROP and systemic inflammation. In this study, we investigated serum cytokines associated with ROP development and severity and assessed their applicability as potential biomarkers of ROP. Methods: This prospective study was conducted at an institutional referral center between 2019 and 2021. To measure the serum levels of 40 inflammatory cytokines in eligible premature patients, we collected their serum samples during the enrollment of patients or the intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents and after 2 and 4 weeks. Results: Fifty patients were enrolled. In patients with type 1 ROP who received anti-VEGF agents (n = 22), the levels of serum intercellular adhesion molecule-1 decreased significantly (p < 0.05) at 4 weeks compared with the baseline level, whereas those of serum granulocyte-macrophage colony-stimulating factor increased significantly (p < 0.05). In patients with ROP who did not require any treatment (n = 14), no significant change was noted in the level of any of the 40 inflammatory cytokines. In control infants without ROP (n = 14), the serum levels of tumor necrosis factor-α, interleukin (IL)-15, and IL-12p40 increased significantly (p < 0.05) at 4 weeks. The changes in the levels of serum inflammatory cytokines did not vary significantly among the aforementioned three groups. A generalized estimating equation indicated that zone 1 ROP, stage 3 ROP, older postmenstrual age, respiratory distress syndrome, necrotizing enterocolitis, and sepsis were associated with the changes in serum cytokine levels. Conclusions: Although significant changes (compared with baseline) were observed in the serum levels of certain inflammatory cytokines in patients with type 1 ROP and infants without ROP, no significant difference in cytokine level fluctuations were noted among the three groups. Changes in serum inflammatory cytokine levels may not predict ROP development or severity. Additional comprehensive studies are warranted to establish their definitive role and significance in ROP, emphasizing the need for continued research in this area.