Impact of Telemedicine on Blood Glucose Control and Ophthalmic Screenings for Patients with Diabetes in Remote Areas During the COVID-19 Pandemic: A Real-World Study in Northern Taiwan.

Introduction: The purpose of this study was to assess the impact of telemedicine on ophthalmic screening and blood glucose control for patients with diabetes in remote areas of Northern Taiwan during the coronavirus disease 2019 (COVID-19) pandemic. Methods: Telemedicine was implemented in Shiding and Wanli Districts using a 5G platform from April 2021 to December 2022. Patients with poorly controlled diabetes received real-time consultations from endocrinologists at Far Eastern Memorial Hospital, 50 km away, for medication adjustment, diet control, and lifestyle recommendations. The study also provided cloud-upload blood glucose meters for self-monitoring and regular medical advice from hospital nurses. Ophthalmic screenings included fundus imaging, external eye image, and intraocular pressure measurement, with instant communication and diagnosis by ophthalmologists through telemedicine. A satisfaction questionnaire survey was conducted. Results: The study enrolled 196 patients with diabetes. Blood glucose and glycosylated hemoglobin levels were significantly reduced after applying telemedicine (p = 0.01 and p = 0.005, respectively). Ophthalmic screenings led to hospital referrals for 16.0% with abnormal fundus images, 15.6% with severe cataract or anterior segment disorders, and 27.9% with ocular hypertension or glaucoma. Fundus screening rates remained high at 86.3% and 80.4% in 2022, mainly using telemedicine, comparable with the traditional screening rate in the past 5 years. The overall satisfaction rate was 98.5%. Conclusions: Telemedicine showed effectiveness and high satisfaction in managing diabetes and conducting ophthalmic screenings in remote areas during the COVID-19 pandemic. It facilitated early diagnosis and treatment of ocular conditions while maintaining good blood glucose control and fundus screening rates.

Adherence to visual field examination in glaucoma patients during the Coronavirus disease 2019 outbreak.

We described the proportion of adherence to the scheduled visual field (VF) examination and the associated factors in glaucoma patients in a tertiary referral center during the Coronavirus disease 2019 (COVID-19) outbreak in Taiwan. Patients with scheduled VF examinations during May 25th to July 12th, 2021, were retrospectively evaluated. Clinical characteristics including type of glaucoma, intraocular pressure (IOP) at the day of arranging VF examinations, prescriptions of anti-glaucoma medications, non-medical glaucoma treatment, length of glaucoma history, mean deviation (MD) of VF defect, and announcement of glaucoma progression were recorded. The associations between the adherence and the clinical factors were analyzed by univariate and multivariate logistic regression. There were 204 patients included, of which 37 patients (18.14%) adhered to VF examinations. A total of 161 patients (78.9%) were diagnosed with open-angle glaucoma (OAG), 27 patients (13.2%) with angle closure glaucoma, and 16 patients (7.8%) with glaucoma suspect. Most of the participants (41.2%) had mild VF defect and had been prescribed with no more than 1 bottle of anti-glaucoma medication. In the multivariate analysis, diagnosis of glaucoma suspect (P = .02) and history of SLT (P = .04) were significantly associated with better adherence. Glaucoma severity and the announcement of glaucoma progression were not significantly associated with adherence to VF examination. The COVID-19 pandemic had greatly influenced the adherence to VF examination in glaucoma patients. This study demonstrated that patients with the diagnosis of glaucoma suspect and history of SLT were more likely to adhere to VF examinations even during the COVID-19 pandemic.

Automated Age-Related Macular Degeneration Detector on Optical Coherence Tomography Images Using Slice-Sum Local Binary Patterns and Support Vector Machine.

Artificial intelligence has revolutionised smart medicine, resulting in enhanced medical care. This study presents an automated detector chip for age-related macular degeneration (AMD) using a support vector machine (SVM) and three-dimensional (3D) optical coherence tomography (OCT) volume. The aim is to assist ophthalmologists by reducing the time-consuming AMD medical examination. Using the property of 3D OCT volume, a modified feature vector connected method called slice-sum is proposed, reducing computational complexity while maintaining high detection accuracy. Compared to previous methods, this method significantly reduces computational complexity by at least a hundredfold. Image adjustment and noise removal steps are excluded for classification accuracy, and the feature extraction algorithm of local binary patterns is determined based on hardware consumption considerations. Through optimisation of the feature vector connection method after feature extraction, the computational complexity of SVM detection is significantly reduced, making it applicable to similar 3D datasets. Additionally, the design supports model replacement, allowing users to train and update classification models as needed. Using TSMC 40 nm CMOS technology, the proposed detector achieves a core area of 0.12 mm2 while demonstrating a classification throughput of 8.87 decisions/s at a maximum operating frequency of 454.54 MHz. The detector achieves a final testing classification accuracy of 92.31%.

Phylogeny, ancestral ranges and reclassification of sand dollars.

Classification of the Class Echinoidea is under significant revision in light of emerging molecular phylogenetic evidence. In particular, the sister-group relationships within the superorder Luminacea (Echinoidea: Irregularia) have been considerably updated. However, the placement of many families remains largely unresolved due to a series of incongruent evidence obtained from morphological, paleontological, and genetic data for the majority of extant representatives. In this study, we investigated the phylogenetic relationships of 25 taxa, belonging to eleven luminacean families. We proposed three new superfamilies: Astriclypeoidea, Mellitoidea, and Taiwanasteroidea (including Dendrasteridae, Taiwanasteridae, Scutellidae, and Echinarachniidae), instead of the currently recognized superfamily Scutelloidea Gray, 1825. In light of the new data obtained from ten additional species, the historical biogeography reconstructed shows that the tropical western Pacific and eastern Indian Oceans are the cradle for early sand dollar diversification. Hothouse conditions during the late Cretaceous and early Paleogene were coupled with diversification events of major clades of sand dollars. We also demonstrate that Taiwan fauna can play a key role in terms of understanding the major Cenozoic migration and dispersal events in the evolutionary history of Luminacea.

Hyperbaric oxygen therapy as rescue therapy for pediatric frosted branch angiitis with Purtscher-like retinopathy: A case report.

Introduction: Frosted branch angiitis (FBA) is an uncommon uveitis characterized by fulminant retinal vasculitis. Purtscher-like retinopathy (PuR) is a rare retinal angiopathy associated with a non-traumatic etiology. Both FBA and PuR can cause profound visual impairments. Case report: We describe the case of a 10-year-old male who presented with sudden bilateral painless visual loss due to FBA with concurrent PuR, with notable viral prodrome 1 month prior to presentation. Systemic investigations revealed a recent herpes simplex virus 2 infection with a high titer of IgM, positive antinuclear antibody (ANA) (1:640), and abnormal liver function tests. After administration of systemic corticosteroids, anti-viral agents, and subsequent immunosuppressive medications, the FBA was gradually alleviated. However, fundoscopy and optical coherence tomography (OCT) revealed persistent PuR and macular ischemia. Hence, hyperbaric oxygen therapy was administered as a rescue strategy, which resulted in gradual bilateral visual acuity improvement. Conclusion: Hyperbaric oxygen therapy may be a beneficial rescue treatment for retinal ischemia secondary to FBA with PuR.

Bilateral Retinal Artery Occlusions and Uveitis as the First Manifestation of Crohn's Disease.

PURPOSE: To present a case of newly diagnosed Crohn's disease, in which retinal artery occlusion (RAO) with uveitis was the first clinical manifestation. CASE DESCRIPTION: A 55-year-old man presented with bilateral blurred vision, with decreased best corrected visual acuity (BCVA) to light perception (right eye, RE) and 20/40 (left eye, LE). Ophthalmological examination revealed bilateral iritis, vitritis, disc edema, and retinal vascular occlusions. Because of concurrent fever and leukocytosis, a systemic infection was highly suspected. However, whole-body imaging was unrevealing. Subsequently, the patient presented with massive bloody stool. Histopathological specimen from emergent hemicolectomy confirmed transmural granulomatous inflammation. Crohn's disease was finally diagnosed. Following treatment, the BCVA recovered to 20/40 (RE) and 20/22 (LE). The systemic condition remained stable after a 3-year follow-up. CONCLUSION: RAO with uveitis is a possible manifestation of Crohn's disease. In complex uveitis cases, clinicians should be aware of inflammatory bowel diseases as an important differential diagnosis.

Computed Tomography Morphology of Affected versus Unaffected Sides in Patients with Unilateral Primary Acquired Nasolacrimal Duct Obstruction.

BACKGROUND: This study aimed to describe the anatomical details of the bony nasolacrimal duct (BNLD) and adjacent nasal structures by analyzing computed tomography (CT) images, and to investigate their effects on the development of primary acquired nasolacrimal duct obstruction (PANDO). METHODS: A total of 50 patients with unilateral PANDO who underwent dacryocystorhinostomy, with a mean age of 57.96 years, were included. The preoperative CT images were reviewed to measure the anteroposterior and transverse diameters of the BNLD at the entrance and exit levels, as well as the minimum transverse diameter along the tract. The sagittal CT images were analyzed to classify the shape of the bony canals into columnar, funnel, flare, and hourglass. The associated paranasal abnormalities, including nasal septum deviation (NSD), sinusitis, angle between the bony inferior turbinate and medial wall of the maxillary sinus, and mucosal thickness of the inferior turbinate, were investigated. RESULTS: Fifty CT images were analyzed, and all parameters measured on both sides of the BNLD were not significantly different between the PANDO and non-PANDO sides, except for the minimum transverse diameter, which was significantly smaller on the PANDO side (p = 0.002). Columnar-shaped BNLD was the most common on both sides. No significant difference was observed in the incidence of paranasal abnormalities between sides; however, deviation of the septum toward the non-PANDO side was more common (67.9%). CONCLUSIONS: A small minimum transverse diameter of the BNLD may be a risk factor for PANDO. The association between nasal abnormalities and PANDO was not remarkable.

Ethambutol optic neuropathy with correspondent chiasmitis manifestation in magnetic resonance imaging.

We present a case of an older patient with toxic chiasmatic optic neuropathy accompanied by bitemporal hemianopia associated with ethambutol use. The patient experienced gradual visual defect recovery that was concurrent with an improvement of chiasmal enhancement in the repeat magnetic resonance imaging performed at his 6-month follow-up. However, his visual field pattern sharply changed to left inferior homonymous quadrantanopia because of a new episode of occipital lobe infarction. After 2 years, the patient's visual function reached the best-corrected visual acuity of 20/20 in both eyes, although he had the sequela of homonymous quadrantanopia related to the infarction. Optical coherence tomography revealed that the loss on the macular ganglion cell-inner plexiform layer was related to retrograde transsynaptic degeneration caused by ethambutol-related chiasmopathy.

The IOP lowering effects of "planning" selective laser trabeculoplasty in open angle glaucoma.

Purpose: To investigate whether the planning of selective laser trabeculoplasty (SLT) influences the intraocular pressure (IOP) in patients with open angle glaucoma (OAG). Methods: In this retrospective case-control study conducted on patients with OAG who planned to undergo SLT treatment (SLT group) or a visual field examination (VF group), we collected the demographic data, IOP on the planning day and on the scheduled day of the SLT treatment or VF examination. ΔIOP was defined as the IOP change between the planning day and the scheduled day. We used multivariable regression analyses and linear mixed model to evaluate the association between the abovementioned factors and ΔIOP in the VF group and the treatment eye (SLTt) and fellow eye (SLTf) of the SLT group. Results: One hundred and fifty-three eyes of 102 patients with OAG were included, of which 51 patients in the SLT group and 51 patients in the VF group. The ΔIOP was -1.92 ± 2.77 mmHg in the SLTt, -0.65 ± 2.47 mmHg in the SLTf and -0.08 ± 1.73 mmHg in the VF group (P < 0.05). Both multivariable regression analysis between the VF and SLTt group and linear mixed model in the SLT group showed significant negative association between the ΔIOP and SLT arrangement (P < 0.05). There was no significant association between ΔIOP and age, gender, baseline IOP, IOP fluctuation, nor SE. Conclusions: The IOP was significantly reduced in patients with OAG after "planning" of SLT treatment, even without actual performing the laser treatment in our retrospective case-control study.

Neuromyelitis Optica Spectrum Disorder: From Basic Research to Clinical Perspectives.

Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory disease of the central nervous system characterized by relapses and autoimmunity caused by antibodies against the astrocyte water channel protein aquaporin-4. Over the past decade, there have been significant advances in the biologic knowledge of NMOSD, which resulted in the IDENTIFICATION of variable disease phenotypes, biomarkers, and complex inflammatory cascades involved in disease pathogenesis. Ongoing clinical trials are looking at new treatments targeting NMOSD relapses. This review aims to provide an update on recent studies regarding issues related to NMOSD, including the pathophysiology of the disease, the potential use of serum and cerebrospinal fluid cytokines as disease biomarkers, the clinical utilization of ocular coherence tomography, and the comparison of different animal models of NMOSD.

Inhibition of Rho-associated protein kinase activity enhances oxidative phosphorylation to support corneal endothelial cell migration.

Corneal endothelial cell (CEC) dysfunction causes corneal edema and severe visual impairment that require transplantation to restore vision. To address the unmet need of organ shortage, descemetorhexis without endothelial keratoplasty has been specifically employed to treat early stage Fuchs endothelial corneal dystrophy, which is pathophysiologically related to oxidative stress and exhibits centrally located corneal guttae. After stripping off central Descemet's membrane, rho-associated protein kinase (ROCK) inhibitor has been found to facilitate CEC migration, an energy-demanding task, thereby achieving wound closure. However, the correlation between ROCK inhibition and the change in bioenergetic status of CECs remained to be elucidated. Through transcriptomic profiling, we found that the inhibition of ROCK activity by the selective inhibitor, ripasudil or Y27632, promoted enrichment of oxidative phosphorylation (OXPHOS) gene set in bovine CECs (BCECs). Functional analysis revealed that ripasudil, a clinically approved anti-glaucoma agent, enhanced mitochondrial respiration, increased spare respiratory capacity, and induced overexpression of electron transport chain components through upregulation of AMP-activated protein kinase (AMPK) pathway. Accelerated BCEC migration and in vitro wound healing by ripasudil were diminished by OXPHOS and AMPK inhibition, but not by glycolysis inhibition. Correspondingly, lamellipodial protrusion and actin assembly that were augmented by ripasudil became reduced with additional OXPHOS or AMPK inhibition. These results indicate that ROCK inhibition induces metabolic reprogramming toward OXPHOS to support migration of CECs.

Changing surface ocean circulation caused the local demise of echinoid Scaphechinus mirabilis in Taiwan during the Pleistocene-Holocene transition.

Abundant fossil specimens of Scaphechinus mirabilis, now occurring mostly in temperate waters, have been found in the Toukoshan Formation (Pleistocene) in Miaoli County, Taiwan. Environmental changes leading to its extirpation (local extinction) have thus far been elusive. Here, we reconstruct past environmental and oceanic conditions off northwest Taiwan by analyzing clumped isotopes, as well as stable oxygen isotopes, of well-preserved fossil echinoid tests collected from the Toukoshan Formation. Radiocarbon dates suggest that these samples are from Marine Isotope Stage 3 (MIS 3). Paleotemperature estimates based on clumped isotopes indicate that fossil echinoids were living in oceanic conditions that range from 9 to 14 °C on average, comparable with the estimate derived for a modern sample from Mutsu Bay, Japan. Notably, this temperature range is ~ 10 °C colder than today's conditions off northwest Taiwan. The substantially lower temperatures during ~ 30 ka (MIS 3) compared to the modern conditions might be due to the rerouting of surface currents off northwest Taiwan when the sea level was ~ 60 m lower than today, in addition to the cooling caused by a lower atmospheric CO2 level during the Last Glacial Period. Colder waters brought here by the China Coastal Current (CCC) and the existence of shallow subtidal zones termed "Miaoli Bay" (mainly located in the present-day Miaoli county) during MIS 3 plausibly sustained generations of S. mirabilis, yielding tens of thousands of fossil specimens in the well-preserved fossil beds. The likely extirpation driver is the drastic change from a temperate climate to much warmer conditions in the shallow sea during the Pleistocene-Holocene transition.

Predictability of 6 Intraocular Lens Power Calculation Formulas in People With Very High Myopia.

Purpose: To investigate the accuracy of 6 intraocular lens (IOL) power calculation formulas in predicting refractive outcomes in extremely long eyes. Setting: Department of Ophthalmology, Far Eastern Memorial Hospital, Taiwan. Design: Retrospective comparative study. Methods: In this retrospective single-center study, we reviewed 70 eyes of 70 patients with axial length (AL) ≥ 28 mm who had received an uneventful 2.2 mm corneal wound phacoemulsification and in-the-bag IOL placement. The actual postoperative refractive results were compared to the predicted refraction calculated with 6 formulas (Haigis, Hoffer Q, Holladay 1, SRK/T, T2, Barrett Universal II formulas) using IOLMaster 500 as optical biometry in the User Group for Laser Interference Biometry (ULIB) constants. Results: Overall, the Haigis and Barrett formulas achieved the lowest level of mean prediction error (PE) and median absolute error (MedAE). Hoffer Q, Holladay 1, SRK/T, and T2 had hyperopic prediction errors (p < 0.05). The Hoffer Q and Holladay 1 had significantly more MedAE between the 6 formulas. After the mean PE was zeroed out, the MedAE had no significant difference between each group. The absolute error tends to be larger in patients with longer AL. The absolute errors were 30.0-37.1% and 60.0-64.3% within 1.0 D of all patients compared to predicted refraction calculated using various formulas. Conclusion: The Haigis and Barrett Universal II formulas had a better success rate in predicting IOL power in high myopic eyes with AL longer than 28 mm using the ULIB constant in this study. The postoperative refractive results were inferior to the benchmark standards, which indicated that the precision of IOL power calculation in patients with high myopia still required improvement.

Ranibizumab reimbursement and treatment patterns for neovascular age-related macular degeneration in Taiwan - Results from the 12-month, observational RENOWNED study.

BACKGROUND: The RENOWNED study investigated the treatment patterns, real-world effectiveness and safety of ranibizumab in Taiwanese patients with neovascular age-related macular degeneration (nAMD) treated with ranibizumab 0.5 mg in accordance with the first reimbursement scheme effective from 2012 to 2014. METHODS: This study was a Phase IV, 12-month, open-label, prospective, observational study conducted in Taiwan. Patients with visual impairment due to nAMD initiating treatment with ranibizumab 0.5 mg were included. The primary endpoint was mean change in best-corrected visual acuity (BCVA) from Baseline at Month 3. RESULTS: Overall, 202 patients with nAMD were included. Mean (standard deviation [SD]) BCVA Early Treatment Diabetic Retinopathy Study letters improved from Baseline (49.6 [21.5] letters) at Month 3 (+4.9 [11.8], P < 0.0001), and at Month 12 (+3.5 [14.1], P = 0.0043). The proportion of patients with nAMD who lost ≥5 letters at Months 3 and 12 was 13.6% (n = 27) and 26.6% (n = 37), respectively. Mean (SD) central retinal thickness decreased from Baseline (320.1 [127.2] µm) with a mean reduction of 49.1 (107.3) µm at Month 3 (P < 0.0001), but was not significant at Month 12 with a mean reduction of 11.6 (115.6) µm (P = 0.2861). Mean (SD) number of ranibizumab injections over 12 months was 3.1 (1.0). A mean treatment interval of 109.5 days was observed between the third and fourth injections. After limited reimbursed ranibizumab injections, 43.8% patients received other treatments. The safety findings are consistent with previous studies. CONCLUSION: Ranibizumab 0.5 mg treatment for 12 months under real-world settings improved visual outcomes in Taiwanese patients with nAMD.

Clinical Manifestations and Implications of Nonneoplastic Uveitis Masquerade Syndrome.

PURPOSE: To investigate the clinical manifestations and systemic and ocular implications of nonneoplastic uveitis masquerade syndrome (NNUMS). DESIGN: Retrospective case series. METHODS: The clinical data of 830 consecutive patients who presented with uveitis at a tertiary referral center in northern Taiwan between August 2013 and August 2020 were analyzed. The clinical characteristics and outcomes of patients with NNUMS were evaluated. RESULTS: Overall, 3.7% of patients were determined to have uveitis masquerade syndrome. Among them, 24 patients (77%; 34 eyes) were diagnosed as having NNUMS. The main presenting anatomical location was posterior uveitis (58.8%). In the NNUMS group, a high chorioretinal involvement rate (94.1%) and delayed diagnosis from symptom onset (45.8% cases were diagnosed after more than 90 days) were found. Multimodal imaging was the major decisive diagnostic factor. Systemic condition alterations requiring urgent treatment were noted in 29.2% of cases. Ocular complications were noted in 58.8% of cases; 60% of those were observed on referral. Following appropriate treatment, visual acuity could be maintained in 88.3% of cases. The 5 major categories of NNUMS were retinal vascular disorders, rhegmatogenous retinal detachment, retinal dystrophy, central serous chorioretinopathy, and uveal effusion syndrome. CONCLUSION: NNUMS is a group of heterogeneous diseases with a complex diagnostic process and significant ocular and systemic effects. High awareness regarding common clinical manifestations is crucial for physicians to make the appropriate diagnosis and management.

Clinical and Epidemiological Profiles of Retinal Vasculitis in Northern Taiwan.

PURPOSE: To investigate the epidemiological and clinical profiles in retinal vasculitis in an Asian cohort. METHODS: A 5-year retrospective study of 487 uveitis patients in a tertiary referral center at northern Taiwan. RESULTS: Overall, 18.5% of the cases were associated with retinal vasculitis (RV). Sarcoidosis and cytomegalovirus retinitis were two leading diagnoses. Cases with RV were younger (mean: 39.7 years), less unilateral (50%), and had more chorioretinal involvement (95.5%). Definite diagnosis was reached in 86.7% of RV cases, of which 38.5% had infectious uveitis. While sole arteritis was presented in 8.9% of cases, 63.3% showed phlebitis, and 27.8% involved both. Three distinctive patterns were associated with a higher likelihood of infection: nodular sheathing, continuous perivascular sheathing (OR 4.79), and continuous fluorescein leakage (OR 4.11). CONCLUSION: The presence of RV, especially arteritis, is highly suggestive of identifiable etiology. Distinctive clinical patterns help differentiation of infectious versus noninfectious causes.

Ocular inflammatory manifestations following COVID-19 vaccinations in Taiwan: A case series.

As a continuing demand for booster shots against SARS-CoV-2, ocular adverse events following the coronavirus disease-2019 (COVID-19) vaccines can cause significant visual impairment, and they warrant a high awareness and detailed documentation of possible ocular inflammatory manifestations. We present a case series of 11 patients presenting with ocular manifestations relevant to vaccine-associated autoimmune response within 6 weeks after the vaccination of the Oxford-AstraZeneca, the Moderna, and Pfizer-BioNTech vaccines at the main tertiary referral center in the most populated and most vaccinated city in Taiwan. Their diagnosis included five acute anterior uveitis, two multiple evanescent white dot syndrome, one probable Vogt-Koyanagi-Harada disease, one anterior scleritis, one relapsed idiopathic panuveitis, and one autoantibody-related central retinal artery occlusion. This report presented a broad spectrum of the ocular inflammatory events following the vaccination of COVID-19. Early recognition of the clinical manifestations mentioned herein with prompt management is crucial in recovering the patients' vision.

Combined intravitreal ranibizumab and posterior subtenon triamcinolone acetonide injections for patients with diabetic macular edema refractory to intravitreal ranibizumab monotherapy.

PURPOSE: The purpose of this study is to compare the efficacy of intravitreal ranibizumab (IVR) alone and concurrent IVR with posterior subtenon triamcinolone acetonide (PSTA) injection for patients with diabetic macular edema (DME) refractory to IVR monotherapy. MATERIALS AND METHODS: We enrolled 43 eyes of 43 patients with DME who received at least three times of IVR, which resulted in poor anatomical responses, with central foveal thickness (CFT) reduction <10% and postinjection CFT >300 µm. All the eyes received initial 3 monthly then pro re nata (PRN) IVR 0.5-mg injections. Twenty eyes continued PRN injections and 23 eyes received combined IVR 0.5 mg and PSTA 40 mg with at least 1-year follow-up. Best-corrected visual acuity (BCVA) and CFT were recorded from 1-month to 1-year follow-up. RESULTS: Following switch to combined therapy, the mean BCVA significantly improved from 0.61 ± 0.32 logarithm of the minimum angle of resolution (logMAR) to 0.45±0.39 logMAR at 6 month (P = 0.003), 0.43±0.35 logMAR at 9 months (P < 0.001), and 0.48±0.45 logMAR at 1 year (P = 0.03). In eyes with IVR alone, no significant VA improvement was noted throughout the year. Significantly better BCVA was noted in the combined group at 6-month, 9-month, and 1-year follow-up compared to IVR-alone group. The timing of combined therapy showed a significant association with 1-year BCVA (t = 3.25, P = 0.018). CONCLUSION: Concurrent IVR and PSTA resulted in significantly better visual outcomes in 1-year follow-up for those refractory to preceding ranibizumab monotherapy for DME. Early addition of PSTA predicted a better visual outcome.