Earticle

Choroidal neovascularization (CNV) is the primary cause of visual defect for the most of patients severely suffering from age-related macular degeneration (AMD). Recent research on drug delivery to the choroid where CNV originates demonstrates that has limitation on a drug penetrated into the outer retina. The objective of this study was to improve a drug delivery system for an integrin-antagonist peptide to the sub-retinal region. We developed nanoparticles that were fabricated by blending polylactic acid/polylactic acid-polyethylene oxide(PLA/PLA-PEO), and water-soluble integrin-antagonist peptide, C16Y, were encapsulated in nanoparticles(C16Y-NP). The PLA/PLA-PEO nanoparticles were 302 ± 85. 1-sized and continuously released C16Y encapsulated into NPs for over 2 weeks in in vitro. The nanoparticles did not exhibit any retinal toxicity as examined by histopathology. Either C16Y-NPs or C16Y peptide solution were separately injected to rodent models 5 or 9 days post laser photocoagulation. Both intravitreal injections of C16Y peptide and C16Y-NPs statistically suppressed CNV (p<0.05) at 5days and 9 days post laser photocoagulation. In the case of C16Y-NPs injection on day 12, however, the area of choroidal neovascularization on the day 12 was smaller than single injection of C16Y peptide solution (p<0.05) due to the short half-life in vitreous body. The result in this paper indicates that sustained release type of drug delivery is important to treat CNV derived from AMD. The intravitreally administered PLA/PLA-PEO nanoparticles encapsulating coumarin were revealed to penetrate the retina and localize to the RPE. These results propose that nanoparticles fabricated by biodegradable polymers are promising materials as carrier and potential drug delivery system may be established for treatment of AMD.

Purpose: To assess the effect of intravitreal and posterior subtenon injections of triamcinolone acetonide (TA) on intraocular pressure (IOP). Methods: we reviewed 42 consecutive eyes after intravitreal TA injection (IVTA) and 43 eyes following posterior subtenon TA injection (PSTA). All cases had a minimum follow-up time of three months. After injection, the value and time of the maximal IOP, the amount of IOP elevation and the needs of the medication were assessed. Results: The IOP increased significantly (p<0.001) from 16.3±2.5 mmHg preoperatively to a mean maximum of 21.7±5.3 mmHg in the IVTA group, and from 15.3±4.5 mmHg to 20.6±3.0 mmHg in the PSTA group. An elevation in the IOP of more than 5 mmHg from the baseline IOP was seen in 52.4% of the IVTA group at a mean time of 3.1 weeks postoperatively, and 44.2% of the PSTA group displayed an IOP elevation at 5.9 weeks. Conclusions: Both developed significant elevations of IOP, but this appeared at a later date in the PSTA group. Careful follow-up after local injection of steroids is necessary.

Purpose: To report the frequency and clinical features of sterile inflammation after intravitreal aflibercept injection in a Korean population. Methods: A single-center, retrospective study was performed in patients who received intravitreal aflibercept from July 2013 through January 2015. Results: A total of four cases of post-injection sterile inflammation were identified from 723 aflibercept injections in 233 patients. Patients presented 1 to 13 days after intravitreal aflibercept injection (mean, 5 days). The mean baseline visual acuity was 20 / 60, which decreased to 20 / 112 at diagnosis but ultimately recovered to 20 / 60. Three cases had inflammatory cells in the anterior chamber (mean, 2.25+; range, 0 to 4+), and all cases had vitritis (mean, 3+; range, 2+ to 4+). No patients had pain. Only one patient underwent anterior chamber sampling (culture negative) and injection of antibiotics. Three of four patients were treated with a topical steroid, and all experienced improvement in their symptoms and signs of inflammation. Conclusions: The overall incidence of sterile inflammation after intravitreal aflibercept injection in a Korean population was 4 of 723 injections (0.55%), or 4 of 233 patients (1.79%). Sterile inflammation after intravitreal aflibercept injection typically presents without pain, and the visual outcomes are generally favorable.

Purpose: This study aims to analyze the annual trends of intravitreal injection (IVI) in South Korea. Methods: This retrospective study examined data from the Health Insurance Review and Assessment Service (HIRA)’s Health and Medical Big Data Open Portal. We investigated the number of patients who underwent IVIs and the total number of IVIs in Korea using the procedure code from 2014 to 2023, categorized by age group and type of healthcare facility. Patients aged under 40 years were excluded from the analysis. Additionally, trends in healthcare expenditures were analyzed. Results: The number of patients undergoing IVI and the total number of IVI increased steadily, resulting in 92,124 patients (178.1 patients per 100,000 persons) and 291,784 injections in 2023, which contributed to an increase in medical expenses. The analysis of 10-year age intervals revealed that patients in their 70s were the most frequent recipients of IVI. The prevalence of IVI at primary healthcare facilities has been steadily increasing, from 20% in 2014 to 33% in 2023. Conclusions: The patients receiving IVI and the total number of IVI have been steadily increasing, particularly in primary healthcare settings. Overall, medical expenses continue to rise. The findings of this study provide valuable evidence for the efficient allocation of medical resources in the future.

Purpose: To evaluate the visual and anatomical outcomes for neovascular age-related macular degenerationwith submacular hemorrhage after intravitreal injections of tenecteplase (TNK), anti-vascular endothelialgrowth factor (VEGF) and expansile gas. Methods: This study was a retrospective clinical case series following 25 eyes of 25 patients. All patients receiveda triple injection using 0.05 mL TNK (50 μg), 0.05 mL anti-VEGF and 0.3 mL of perfluoropropane gas. Retreatment with anti-VEGF was performed as needed. Preoperative and postoperative best-corrected visualacuity and central retinal thickness were analyzed. Results: The mean logarithm of the minimum angle of resolution of best-corrected visual acuity improved significantlyfrom 1.09 ± 0.77 at baseline to 0.52 ± 0.60 at 12 months (p < 0.001). The mean central retinal thicknessalso improved significantly from 545 ± 156 at baseline to 266 ± 107 at 12 months (p < 0.001). A visualimprovement of 0.3 logarithm of the minimum angle of resolution unit or more was achieved in 15 eyes (60%). During the 12 postoperative months, an average of 4.04 intravitreal anti-VEGF injections was applied. Conclusions: A triple injection of TNK, anti-VEGF, and a gas appears to be safe and effective for the treatmentof submacular hemorrhage secondary to neovascular age-related macular degeneration.

Purpose: This study compared serum vascular endothelial growth factor (VEGF) concentration between patientsgiven the bilateral and unilateral intravitreal injections of bevacizumab. Methods: In a prospective manner, serum VEGF levels in treatment-naive patients with age-related macular degenerationwho underwent bilateral or unilateral intravitreal injections of bevacizumab were investigated. Afterinformed consent, peripheral blood was collected from in patients who underwent bilateral or unilateral intravitrealinjection of bevacizumab before and 1 month after the injection. Serum VEGF levels were measured byenzyme-linked immunosorbent assay after centrifugation. In addition, best-corrected visual acuity (BCVA) andcentral retinal thickness (CRT) before and 1 month after the injection were compared between each group. Results: Twenty patients received bilateral injections (40 eyes) and 20 patients received unilateral injections. The VEGF concentrations (pg/mL) before the bilateral injection were 235.75 ± 183.16 and 252.53 ± 233.52 forthe unilateral injection. They were significantly reduced to 153.88 ± 113.26 and 189.42 ± 251.72 after 1 month,respectively (p = 0.037 and 0.019), which are showing no significant difference between the two groups (p =0.771). And there were no significant intergroup difference in pre- and postoperative BCVA and CRT. Conclusions: The bilateral simultaneous intravitreal injection of bevacizumab did not differ greatly from unilateralintravitreal injection in the influence on serum VEGF levels and the therapeutic outcome.

Currently, the two primary patient-derived xenograft (PDX) models of glioblastoma are established through intracranial or subcutaneous injection. In this study, a novel PDX model of glioblastoma was developed via intravitreal injection to facilitate tumor formation in a brain-mimicking microenvironment with improved visibility and fast development. Glioblastoma cells were prepared from the primary and recurrent tumor tissues of a 39-year-old female patient. To demonstrate the feasibility of intracranial tumor formation, U-87 MG and patient-derived glioblastoma cells were injected into the brain parenchyma of Balb/c nude mice. Unlike the U-87 MG cells, the patient-derived glioblastoma cells failed to form intracranial tumors until 6 weeks after tumor cell injection. In contrast, the patientderived cells effectively formed intraocular tumors, progressing from plaques at 2 weeks to masses at 4 weeks after intravitreal injection. The in vivo tumors exhibited the same immunopositivity for human mitochondria, GFAP, vimentin, and nestin as the original tumors in the patient. Furthermore, cells isolated from the in vivo tumors also demonstrated morphology similar to that of their parental cells and immunopositivity for the same markers. Overall, a novel PDX model of glioblastoma was established via the intravitreal injection of tumor cells. This model will be an essential tool to investigate and develop novel therapeutic alternatives for the treatment of glioblastoma.

Purpose: To improve the treatment efficiency of optic nerve diseases by delivering therapeutic materials to the optic nerve directly. Methods: We tried to optimize liposomal composition to deliver a payload to the optic nerve efficiently when it is injected intravitreally. After loading dexamethasone into this liposome, we tested the therapeutic effect of liposomes in this treatment using a murine model of ischemic optic neuropathy. Results: Our optimized liposome can deliver its payload to the optic nerve more efficiently than other tested compositions. Moreover, dexamethasone-loaded liposomes had a significant therapeutic effect in a murine model of ischemic optic neuropathy. Conclusions: Here, we demonstrate the optimal composition of liposomes that could efficiently deliver intravitreally injected exogenous compounds to the optic nerve. We expect that the intravitreal injection of liposomes with the suggested composition would improve the delivery efficacy of therapeutic compounds to the optic nerve.

Purpose: To evaluate the effects of posterior subtenon triamcinolone acetonide injection on refractory diabeticmacular edema (DME) after intravitreal bevacizumab (IVB) injection failure. Methods: Patients with DME and central subfield thickness (CST) >300 μm who did not respond to IVB injectionswere retrospectively included. Specifically, we enrolled patients who were diagnosed with refractoryDME and who experienced an increase in CST after 1 to 2 IVB injections or no decrease after ≥3 consecutiveIVB injections. One clinician injected 20 mg of triamcinolone acetonide into the posterior subtenon space. Allpatients received ophthalmic examinations at baseline and at 2, 4, and 6 months post-baseline. Examinationsincluded Snellen visual acuity, intraocular pressure, and spectral-domain optical coherence tomography. Results: Forty eyes of 34 patients were included. The average baseline CST was 476 μm. The average CSTdecreased to 368 μm at 2 months, 374 μm at 4 months, and 427 μm at 6 months (p < 0.001 for all results, Wilcoxonsigned-rank test). The average intraocular pressure increased from 15.50 to 16.92 mmHg at 2 monthsbut decreased to 16.30 mmHg at 4 months and 15.65 mmHg at 6 months. Logarithm of the minimum angle ofresolution visual acuity improved from 0.56 to 0.50 at 2 months (p = 0.023), 0.50 at 4 months (p = 0.083), and0.48 at 6 months (p = 0.133, Wilcoxon signed-rank test). No complications were detected. Conclusions: Posterior subtenon triamcinolone acetonide is an effective and safe treatment for reducing CSTin DME refractory to IVB.

Purpose: To compare the long-term efficacy and safety of intravitreal triamcinolon with or without rescue lasertherapy (intravitreal triamcinolone injection [IVTA] group), bevacizumab with or without rescue laser treatment(intravitreal bevacizumab injection [IVB] group), or a combination of both with or without rescue laser therapy(IVTA + IVB group), with standard care for patients with macular edema secondary to branch retinal vein occlusion(BRVO). Methods: We reviewed the medical records of 151 patients treated with intravitreal injection with or without rescuelaser for treatment of macular edema caused by BRVO, and who were followed up at 1, 3, 6, 12, and 24months. During the observation period, rescue grid laser or repeated intravitreal injection with initial drug wasperformed if recurrence of macular edema was confirmed. Visual acuity, change in visual acuity, and intraocularpressure were compared in each phase. Results: Totals of 16%, 5.6%, and 0% of participants in the three groups showed significant visual loss of morethan three lines of the Snellen chart at last follow-up. The IVTA group was the least effective treatment modality,with statistical significance. The development rates of elevated intraocular pressure were similar among thegroups. Conclusions: Although IVTA yielded effects similar to those of standard grid photocoagulation based on theStandard Care vs Corticosteroid for Retinal Vein Occlusion study, IVB or IVTA + IVB with or without rescuelaser treatment resulted in improvement in visual acuity at 24 months after the start of treatment and was associatedwith few serious adverse side effects. Thus, these approaches could be useful for treating macularedema arising secondary to BRVO.

Purpose: To investigate cases of vitreous opacity (VO) similar to asteroid hyalosis (AH) after intravitreal brolucizumab injection. Methods: A retrospective chart review was conducted to identify cases showing VO similar to AH among patients who received intravitreal brolucizumab injections at our retinal clinic from January 2022 to January 2023. Results: A total of 220 brolucizumab injections were administered at our hospital. VO, showing yellow-white brilliant reflective particles, was found in six patients (2.7%). When VO occurred, all patients complained of floaters, although none of them complained of other symptoms including decreased visual acuity, pain, or conjunctival redness. The mean number of brolucizumab injections was 2.57 ± 2.38. No significant visual impairment was observed while VO was present. VO improved in all cases, and four cases improved without any treatment. The mean interval from onset to disappearance of VO was 8.0 ± 3.1 weeks. Conclusions: VO, similar to AH, can occur with a relatively high probability after intravitreal brolucizumab injections. Patients complained of severe floaters, but VO was not accompanied by other symptoms including vision impairment, injection, and pain. The VO disappeared after approximately 4 to 14 weeks. In case that other inflammatory findings are not severe, close follow-up without treatment may be sufficient. If a patient complains of floaters after an intravitreal brolucizumab injection, close fundus observation is necessary to evaluate the VO.

We report a case of cytomegalovirus (CMV) retinitis after intravitreal bevacizumab injection. A 61-year-old woman with diabetic macular edema developed dense vitritis and necrotizing retinitis 3 weeks after intravitreal bevacizumab injection. A diagnostic vitrectomy was performed. The undiluted vitreous sample acquired by vitrectomy was analyzed by polymerase chain reaction and culture. Polymerase chain reaction of the vitreous was positive for CMV DNA. Other laboratory results did not show evidence of other infectious retinitis and systemic immune dysfunction. Human immunodeficiency virus antibodies were also negative. After systemic administration of ganciclovir, retinitis has resolved and there has been no recurrence of retinitis during the follow-up period of 12 months. Ophthalmologists should be aware of potential risk for CMV retinitis after intravitreal bevacizumab injection.

A 56-year-old Korean woman presented with decreased visual acuity of the right eye. She had a history of two pho-todynamic therapy treatments for choroidal neovascularization (CNV) due to angioid streaks in her left eye with cen-tral scarring and low visual acuity. She was diagnosed with subfoveal CNV due to angioid streaks in her right eye and treated with six intravitreal bevacizumab (1.25 mg / 0.05 mL) injections over one year. Best corrected visual acuity improved from 20 / 125 at baseline to 20 / 50 at the final visit. The area of CNV had changed into a fibrotic scar by the final visit, and fluorescein angiography and indocyanine green angiography revealed no evidence of leakage. Optical coherence tomography showed that central macular thickness decreased from 311 μm at baseline to 203μm with complete resolution of subretinal and intraretinal fluid at the final visit. Intravitreal bevacizumab for CNV as-sociated with angioid streaks prevented the progression of disease and resulted in the improvement of visual acuity after one year of follow-up in our patient.

Purpose: To investigate the short-term effects of panretinal photocoagulation (PRP) combined with an intravitreal injection of Avastin® (bevacizumab) as an adjuvant to high-risk proliferative diabetic retinopathy (PDR). Methods: The data was collected retrospectively from the eyes of high-risk PDR patients, which were divided into two groups. One eye was treated with only PRP (PRP only group) and the fellow eye of same patient was treated with both PRP and intravitreal bevacizumab injection (Adjuvant group). Best corrected visual acuity (BCVA), IOP (intraocular pressure), and new vessel (NV) size in fluorescein angiography were recorded immediately and at the six-week follow- up visit. Adverse events associated with intravitreal injection were investigated. Results: Of 12 patients with high-risk PDR, five were male and seven were female. There were no statistically significant BCVA or IOP changes after treatment in either group (p=0.916, 0.888). The reduction of NV size was found in both groups, but NV size in the adjuvant group showed a greater decrease than that of the PRP only group (p=0.038). Three patients had adverse events after intravitreal injection. Two patients had mild anterior uveitis and one patient had a serious complication of branched retinal artery obstruction (BRAO). Conclusions: Intravitreal bevacizumab injection with PRP resulted in marked regression of neovascularization compared with PRP alone. One serious side effect, BRAO, was noted in this study. Further studies are needed to determine the effect of repeated intravitreal bevacizumab injections and the proper number of bevacizumab injections as an adjuvant.

Purpose: To evaluate 2-year outcomes of intravitreal aflibercept injection for neovascular age-related macular degeneration (nAMD) treated with “observe before treat-and-extend (O-TAE)” strategy in the real-world setting. Methods: This retrospective study included treatment-naive nAMD patients treated with aflibercept using O-TAE regimen and followed up for more than 2 years. Patients were observed bimonthly to check recurrence after three monthly loading injections. In case of recurrence, treatment was resumed using the TAE regimen starting from the fourth injection. In case of nonrecurrence, observation was continued. Best-corrected visual acuity (BCVA), central macular thickness (CMT), number of injections, TAE intervals, and proportion of recurrence after dry-up following three loadings were analyzed. Results: A total of 38 eyes of 34 patients were included. Follow-up period was 37.0 ± 11.0 months. BCVA by logarithm of minimal angle of resolution improved from 0.33 ± 0.29 at baseline to 0.24 ± 0.23 in the first year (p = 0.010) and 0.25 ± 0.22 in the second year (p = 0.054). CMT decreased significantly from 357.43 ± 74.53 μm at baseline to 269.62 ± 48.12 μm in the first year (p < 0.001) and 279.14 ± 54.64 μm in the second year (p < 0.001). Number of injections were 5.11 ± 1.69 in the first year and 3.84 ± 2.39 in the second year. The percentage of eyes with a TAE interval of ≥12 weeks was 37.0% in the first year and 34.4% in the second year. Of the 36 eyes that dried up after three loadings, 28 eyes (77.8%) recurred, and the average period of recurrence was 6.5 months. The remaining eight eyes (22.2%) had no recurrence during the mean follow-up period of 29.7 months. Conclusions: This study showed that the newly suggested O-TAE strategy can reduce the treatment burden significantly reducing the number of injections while improving BCVA and CMT in the first and second year.

Purpose: To evaluate the changes in multifocal electroretinogram (mfERG) and optical coherence tomography (OCT) after intravitreal bevacizumab injection in the treatment of age-related macular degeneration (AMD). Methods: Twenty-one eyes with choroidal neovascularization secondary to AMD were studied before and after intravitreal bevacizumab injection for best corrected visual acuity (BCVA), OCT, and mfERG. Results: The BCVA improved, while central macular thickness and total macular volume in OCT decreased after intravitreal bevacizumab injection (p = 0.03, 0.01, and 0.01, respectively). In mfERG, the amplitude of P1, and implicit time of P1 and N1 indicated a statistically significant improvement of retinal response after intravitreal bevacizumab injection. Conclusions: There is a potential role for mfERG in evaluating the effect on retinal function of intravitreal bevacizumab injection.

A 68-year-old woman presented with a visual field defect in her right eye. The fundus of her right eye showed multiple telangiectatic vessels, retinal hemorrhages, and subretinal exudates in the inferior peripheral retina. Nine months later, the subretinal exudates extended to the fovea despite treatment with laser photocoagulation. Cryotherapy was not possible at the time because of the posterior location of the retinal telangiectatic vessels. She was treated with a combination of photodynamic therapy (PDT) and intravitreal bevacizumab injection: three injections were given at 2-month intervals. After this combined therapy, her right fundus revealed a significant regression of abnormal retinal vessels and subretinal exudates. A fluorescein angiography showed no leakage from the abnormal retinal vessels. At 9 months after the combined therapy, she was able to maintain a stable visual acuity and visual field. This is the first case report that demonstrates the efficacy of the combined treatment of PDT and intravitreal bevacizumab injection in Coats's disease. This combined therapy is a kind of treatment modality for adult Coats’ disease in cases which cryotherapy cannot be employed and are refractory to laser photocoagulation.