Short-Term Safety and Efficacy of Intravitreal Brolucizumab Injections for Neovascular Age-Related Macular Degeneration: A Multicenter Retrospective Real-World Study.

INTRODUCTION: The aim of the study was to determine the short-term real-world safety and efficacy of intravitreal brolucizumab injections in Korean patients with neovascular age-related macular degeneration (nAMD). METHODS: This multicenter retrospective study involved 294 eyes (treatment naïve 20 eye [6.8%] and nontreatment naïve 274 eyes [93.2%]) of 290 patients from 13 hospitals or retinal centers in South Korea. Patients with nAMD who received brolucizumab injection(s) between April 1 and November 30, 2021, with a follow-up ≥1 month, were included. Primary outcomes were safety, incidence of intraocular inflammation (IOI), and potential risk factors. The secondary outcome was efficacy, i.e., change in best-corrected visual acuity (BCVA) and optical coherence tomography-measured macular thickness and retinal fluid. RESULTS: The mean age was 71.63 ± 8.66. The follow-up period was 2.38 ± 0.79 months. The mean number of brolucizumab injections during the follow-up was 1.52 ± 0.58. The overall incidence of IOI was 13.9% (n = 41 eyes). Most IOI cases were of anterior uveitis (8.8%, 26 eyes), followed by retinal vasculitis (2.4%, seven eyes) and occlusive retinal vasculitis (0.3%, one eye). Most eyes showed IOI resolution (n = 40, 97.5%) and BCVA restoration (n = 39, 95.1%) with or without corticosteroid treatment during the follow-up. Age, sex, IOI history, or other anti-vascular endothelial growth factor injection histories were not associated with the occurrence of IOI. However, only thin subfoveal choroidal thickness (SFCT) was associated with the occurrence of IOI (odds ratio = 0.995, p = 0.020). BCVA at 1 month improved from baseline (baseline 0.518 ± 0.356 vs. 1 month 0.503 ± 0.383, p = 0.023), but the improvement was not maintained. Anatomical improvement was significant after 3 months. CONCLUSION: In Korean patients with nAMD, the incidence of IOI following brolucizumab injections was 13.9%. IOI was well-controlled with or without steroid treatment. Most IOI eyes (95.1%) were restored to the level of vision before. IOI occurrence and occlusive vasculitis was rare. In the short term, brolucizumab injection effectively improved vision at 1 month and dried retinal fluid for 3 months.

Brain-derived neurotrophic factor levels and macular ganglion cell-inner plexiform layer thickness in macular telangiectasia type 2.

PURPOSE: To determine brain-derived neurotrophic factor (BDNF) levels in the serum and aqueous humor (AH) and assess the relationship between BDNF levels and the thickness of the macular ganglion cell-inner plexiform layer (GCIPL) in macular telangiectasia type 2 (MacTel). METHODS: This study included 25 patients with MacTel (MacTel group) and 25 control subjects (control group). The levels of BDNF in the serum and AH were tested using an enzyme-binding immunosorbent assay. GCIPL thickness was measured by segmentation analysis using optical coherence tomography (OCT). RESULTS: There was no significant difference in the mean serum BDNF levels between the MacTel and control groups (p = 0.145). The average BDNF level in the AH was significantly lower than that in the control group (p = 0.026). OCT segmentation analyses revealed that the minimum GCIPL thickness was significantly lower in the MacTel group than in the control group (p = 0.039). In the correlation analysis of BDNF levels with GCIPL thickness, significant correlations existed between the BDNF level of the AH and minimum GCIPL thickness in the MacTel group. CONCLUSION: The concentration of BDNF in the AH was decreased in the MacTel group, and this reduction was related to the minimum GCIPL thickness. The low BDNF levels detected in the MacTel group may have resulted in thinning of the GCIPL due to the loss of retinal ganglion cells.

Serum and aqueous humor levels of brain-derived neurotrophic factor in patients with primary open-angle glaucoma and normal-tension glaucoma.

PURPOSE: This study was designed to compare the levels of brain-derived neurotrophic factor (BDNF) in the serum and aqueous humor (AH) of patients with primary open-angle glaucoma (POAG) and normal-tension glaucoma (NTG). METHODS: This prospective, observational study consists of 30 patients with POAG, 30 patients with NTG, and 30 healthy controls. The serum and AH BDNF levels were assessed using an enzyme-linked immunosorbent assay. RESULTS: BDNF levels in serum and AH were markedly lower in the glaucoma groups (POAG and NTG) than in the control group (p < 0.05). When comparing the NTG and POAG groups, the average serum BDNF level was significantly lower in the NTG group than in the POAG group (p < 0.05). The difference in the mean BDNF levels in AH between the POAG and NTG groups was not statistically significant. (p = 0.538). CONCLUSION: We confirmed that serum BDNF levels were lower in patients with NTG than in those with POAG. BDNF could be a causative systemic biomarker in NTG.

23-gauge transconjunctival vitrectomy in eyes with pre-existing functioning filtering blebs.

BACKGROUND: We investigated the outcome of 23-gauge transconjunctival pars plana vitrectomy (23G PPV) for the treatment of vitreoretinal disorder in patients with prior trabeculectomy. METHODS: We retrospectively reviewed medical records of 23G PPV in 11 eyes that had functioning filtering blebs after trabeculectomy. The main outcome measures were the visual acuity, intraocular pressure (IOP) and subconjunctival fluid height in bleb by anterior segment optical coherence tomography (OCT) before and after the surgery. RESULTS: Eyes that had 23G PPV showed improvement of visual acuity after the surgery (P =0.003). Mean IOP was 13.82 mmHg before 23G PPV and 15.82 mmHg at 6 months postoperatively, which was statistically insignificant (P = 0.758). The bleb was observed before and after surgery using anterior segment OCT, and the difference in subconjunctival fluid was not statistically significant (P =0.172). CONCLUSIONS: 23G PPV did not adversely affect bleb function in eyes with prior trabeculectomy.

Long-term efficacy and safety of brolucizumab in neovascular age-related macular degeneration: A multicentre retrospective real-world study.

PURPOSE: To investigate the long-term efficacy and safety of intravitreal brolucizumab (BRZ) injections in patients with typical neovascular age-related macular degeneration (typical nAMD) and polypoidal choroidal vasculopathy (PCV). METHODS: This multicentre retrospective study included 401 eyes of 398 patients with nAMD who received BRZ injection(s), with a follow-up duration of ≥12 months. Changes in best-corrected visual acuity (BCVA), retinal fluid evaluation and central subfield thickness (CST) on optical coherence tomography were assessed. The efficacy of BRZ was compared between typical nAMD and PCV groups. RESULTS: Analyses were conducted with 280 eyes of 278 patients with typical nAMD and 121 eyes of 120 patients with PCV (mean age, 71.1 ± 8.6 years). 29 eyes (7.2%) were treatment naïve. The mean follow-up period was 15.3 ± 2.8 months; the mean number of BRZ injections within 1 year was 4.5 ± 1.7. BCVA was maintained during the follow-up period, and CST significantly improved from the first injection month and was maintained for 12 months in both the typical nAMD and PCV groups. The dry macula proportion increased from 2.7% at baseline to 56.1% at 1 month and 42.9% at 12 months. Among the 18 eyes that underwent indocyanine green angiography both before and after treatment, 10 (55.6%) showed polyp regression. Overall, the incidence of intraocular inflammation (IOI), retinal vasculitis and occlusive retinal vasculitis was 9.4% (38 eyes), 1.2% (5 eyes) and 0.5% (2 eyes), respectively. IOI occurred from the first to the sixth injections, with an average IOI onset of 28.5 ± 1.4 days. All eyes achieved IOI resolution, although the two eyes with occlusive retinal vasculitis showed a severe visual decline after IOI resolution. CONCLUSION: Brolucizumab was effective in maintaining BCVA and managing fluid in eyes with nAMD for up to 1 year, exhibiting a high polyp regression rate. However, the not uncommon incidence of IOI and the severe visual decline caused by the rare occlusive retinal vasculitis following BRZ treatment underscore the importance of careful monitoring and timely management.

Comparison of brain-derived neurotrophic factor among subtypes of exudative age-related macular degeneration.

PURPOSE: To compare the levels of brain-derived neurotrophic factor (BDNF) in serum and aqueous humor (AH) in eyes with typical neovascular age-related macular degeneration (tAMD), polypoidal choroidal vasculopathy (PCV), and retinal angiomatous proliferation (RAP). METHODS: This prospective study included 20 patients with tAMD, 20 patients with PCV, 20 patients with RAP, and 20 healthy controls. BDNF levels in the serum and AH were assessed using enzyme-linked immunosorbent assay. RESULTS: Serum and AH BDNF levels were significantly lower in the age-related macular degeneration groups (tAMD, PCV, and RAP) than in the control group (p < 0.05). There was no significant difference in the mean BDNF levels in the serum and AH among the different nAMD subtypes (p = 0.538). CONCLUSIONS: We confirmed that serum and AH BDNF levels were independent of the nAMD subtype.

Brain-derived neurotrophic factor in non-proliferative diabetic retinopathy with diabetic macular edema.

PURPOSE: To investigate aqueous humor (AH) and serum levels of brain-derived neurotrophic factor (BDNF) in non-proliferative diabetic retinopathy (NPDR) patients with diabetic macular edema (DME). METHODS: The prospective study consists of 20 patients with DME NPDR, 20 patients with no-DME NPDR, and 20 healthy control subjects. Serum and AH samples were obtained during cataract surgery and intravitreal injection. Serum and AH levels of BDNF were measured by enzyme-linked immunosorbent assay. RESULTS: The mean serum levels of BDNF were lower in both NPDR groups compared to the control group (DME NPDR group, p = 0.015; no-DME NPDR group, p = 0.024). Furthermore, the mean serum level of BDNF was lower in the DME NPDR group compared to the no-DME NPDR group (p = 0.041). The mean AH levels of BDNF were significantly reduced in both NPDR groups compared to the control group (DME NPDR group, p < 0.001; no-DME NPDR group, p = 0.006). Further, the mean AH level of BDNF was significantly lower in the DME NPDR group compared to the no-DME NPDR group (p = 0.037). CONCLUSION: Serum and AH levels of BDNF were reduced in NPDR patients with DME than without DME.

Differential Expression of BDNF and BIM in Streptozotocin-induced Diabetic Rat Retina After Fluoxetine Injection.

BACKGROUND: Chronic diabetic retinopathy (DR) is a diabetic complication that causes blindness. Brain-derived neurotrophic factor (BDNF) expression is induced by fluoxetine. We observed the effects of fluoxetine on a streptozotocin (STZ)-induced diabetic rat model in this study. MATERIALS AND METHODS: Rats were divided into three groups: Control, diabetic (65 mg/kg STZ injection), and diabetic with fluoxetine injection (20 mg/kg/week, six times). Western blotting was performed using anti-BDNF and anti-hexaribonucleotide-binding protein-3. Expression of BCL2 apoptosis regulator-like protein 11 (BIM) was analysed using a reverse transcription-polymerase chain reaction. RESULTS: BDNF levels were significantly higher in the diabetic group treated with fluoxetine than in the untreated diabetic group. BIM expression was higher in the diabetic group than in the control group. BIM gene expression was lower in fluoxetine-treated diabetic group than in the untreated diabetic group. CONCLUSION: Fluoxetine had an anti-apoptotic effect with upregulation of BDNF expression in retina of rats with STZ-induced diabetes.

Methodology and Rationale for Ophthalmic Examinations in the Seventh and Eighth Korea National Health and Nutrition Examination Surveys (2017-2021).

This report provides a detailed description of the methodology for ophthalmic examinations according to the Korea National Health and Nutrition Examination Survey (KNHANES) VII and VIII (from 2017 to 2021). The KNHANES is a nationwide survey which has been performed since 1998 in representatives of whole Korean population. During the KNHANES VII and VIII, in addition to the ophthalmic questionnaire, intraocular pressure measurement, visual field test, auto refractometry, axial length and optical coherence tomography measurements were included. This new survey will provide not only provide normative and pathologic ophthalmic data including intraocular pressure, refractive error, axial length, visual field and precise measurement of anterior segment, macula and optic nerve with optical coherence tomography, but also a more accurate diagnosis for major adult blindness diseases, including age-related macular degeneration, diabetic retinopathy, glaucoma, and other ocular diseases, for the national Korean population.

Methotrimeprazine-induced corneal deposits and cataract revealed by urine drug profiling test.

Two schizophrenic patients who had been taking medication for a long period presented with visual disturbance of 6-month duration. Slit-lamp examination revealed fine, discrete, and brownish deposits on the posterior cornea. In addition, bilateral star-shaped anterior subcapsular lens opacities, which were dense, dust-like granular deposits, were noted. Although we strongly suspected that the patient might have taken one of the drugs of the phenothiazine family, we were unable to obtain a history of medications other than haloperidol and risperidone, which were taken for 3 yr. We performed a drug profiling test using urine samples and detected methotrimeprazine. The patient underwent surgery for anterior subcapsular lens opacities. Visual acuity improved in both eyes, but the corneal deposits remained. We report an unusual case of methotrimeprazine-induced corneal deposits and cataract in a patient with psychosis, identified by using the urine drug profiling test.

Immunoreactivity of MAPK Signaling in a Rat Model of Intrauterine Growth Retardation Induced by Uterine Artery Ligation.

BACKGROUND/AIM: Intrauterine growth retardation (IUGR) causes very low birth weight and is related to the morbidity and mortality of the newborn. In our previous study, expression of brain-derived neurotrophic factor (BDNF) was found reduced in the cerebral cortex and dentate gyrus of fetuses with IUGR. BDNF protected cortical neurons against hypoxic injury via activation of the extracellular signal-related kinase (ERK) pathway. The aim of the current study was to observe the immunoreactivity of ERK in mature neurons and proliferating cells. MATERIALS AND METHODS: Uterine artery ligation was performed at 17 days of gestation (dg). Rat fetuses were obtained at 21 dg using cesarean section. Fetuses were designated either to the growth retardation (GR) group when removed from the horn with uterine artery ligation, or to the control group when removed from the other horn with the untied artery. Immunohistochemistry was performed with primary antibodies on paraffin-embedded forebrain sections. RESULTS: The density and proportion of cells expressing PCNA, ERK, and phosphate ERK in the subventricular zone (SVZ) was not different between the control and GR group. The density and proportion of NeuN- and phosphate ERK-positive cells in the cerebral parietal cortex was lower in the GR group, compared to the control group. CONCLUSION: Although IUGR had no effect on the proliferation of cells in the SVZ, it reduced neuronal survival in the cerebral parietal cortex, which was associated with the decrease of pERK-positive cell density and proportion in the cerebral cortex.

Differential Expression of Vascular Endothelial Growth Factor in the Cortex and Hippocampus upon Cerebral Hypoperfusion.

BACKGROUND/AIM: Vascular endothelial growth factor (VEGF) provides tolerance against ischemic brain injury, yet, the pattern of VEGF expression in the neurogenic zones following chronic cerebral hypoperfusion has not been studied. Here we evaluated the immunoreactivity of VEGF in a rat model of chronic cerebral hypoperfusion. MATERIALS AND METHODS: Chronic hypoperfusion was induced by bilateral common carotid artery ligation in rats. Immunohistochemistry was performed against hypoxia-inducible factor-1α (HIF-1α) and VEGF on brain sections. RESULTS: The density of HIF1α-positive cells in the hypoxia group was increased in the cerebral cortex and hippocampus. Further, the density of VEGF-positive cells was significantly higher in the hypoxia group compared to the control group in the cerebral cortex whereas it was similar in the subventricular zone, and in the dentate gyrus in the hippocampus between the two groups. CONCLUSION: The pattern of VEGF expression varies in different brain regions following chronic cerebral hypoperfusion.

Combined treatment of phacoemulsification and single-port limited pars plana vitrectomy in acute angle-closure glaucoma.

AIM: To evaluate the efficacy of combined treatment of phacoemulsification (PE) and micro-incisional single-port transconjunctival limited pars plana vitrectomy (PPV) in acute angle-closure glaucoma (AACG). METHODS: A retrospective study included 26 patients who underwent PE diagnosed with AACG. Among them, 16 patients (16 eyes) underwent PE alone, 10 patients (10 eyes) underwent combined limited vitrectomy and PE. Then we compared intraocular pressure (IOP), anterior chamber angle, anterior chamber depth, central corneal thickness and corneal endothelial cell count before and after surgery, and effective PE time during cataract surgery. RESULTS: Effective PE time was shorter in the combined surgery group than in the single surgery group (P=0.040). There was no statistically significant difference in IOP and best-corrected visual acuity between the two groups postoperatively. At 6mo postoperatively, there was no difference in the anterior chamber angle, anterior chamber depth, and central corneal thickness between two groups, but corneal endothelial cell count was higher in the combined surgery group than in the single surgery group (P=0.046). No complication such as vitreoretinal disease, endophthalmitis, bullous keratopathy was noted. CONCLUSION: Combined micro-incisional single-port transconjunctival limited PPV and PE are more effective and safer than PE alone because of less operation time and fewer complications for management of AACG.

Correlation between macular ganglion cell-inner plexiform layer thickness and visual acuity after resolution of the macular edema secondary to central retinal vein occlusion.

AIM: To examine the thickness of the ganglion cell-inner plexiform layer (GCIPL) in eyes with resolved macular edema (ME) in non-ischemic central retinal vein occlusion (CRVO), applying spectral-domain optical coherence tomography (SD-OCT), and its relationship with visual acuity. METHODS: The retrospective observational case-control study included 30 eyes of non-ischemic CRVO patients with resolved ME (ME eyes) after treatment, and 30 eyes of non-ischemic CRVO patients without ME (non-ME eyes). The macular GCIPL thickness, peripapillary retinal nerve fiber layer (pRNFL) thickness and central macular thickness (CMT) were measured on a SD-OCT scan. Linear regression analyses were performed to determine the correlation between the thickness of each and the visual acuity (VA). RESULTS: No significant difference in average GCIPL thickness, mean pRNFL thickness and CMT were observed between ME group and non-ME group (P=0.296, 0.183, 0.846). But, minimum GCIPL thickness was reduced in ME eyes compared with non-ME eyes (P=0.022). Final VA significantly correlated with the minimum GCIPL thickness in ME eyes (r=-0.482, P=0.007), whereas no correlation was found with average GCIPL thickness, average pRNFL thickness and mean CMT. CONCLUSION: Minimum GCIPL thickness is reduced in ME eyes compared with non-ME eyes, and correlated with the VA in non-ischemic CRVO. These results propose that inner retinal damage occurring in patients with ME secondary to non-ischemic CRVO may lead to permanent visual defect after treatment.

Comparative quantification of plasma TDRD7 mRNA in cataract patients by real-time polymerase chain reaction.

PURPOSE: To investigate the relationship between plasma TDRD7 mRNA and lens transparency, and to evaluate plasma TDRD7 mRNA as a potential marker for cataracts and its sub-type by quantitatively analyzing human peripheral blood. METHODS: Plasma RNA was extracted from 40 patients with cataracts, and 30 normal controls of matched age and gender. Blood cholesterol and fasting glucose were measured, and the RNA extracted from the sample was synthesized into cDNA. After polymerase chain reaction, the results were compared after quantifying the TDRD7 mRNA using ABL1 mRNA for normalization. We analyzed the relative gene expression data via the ΔΔCt method. RESULTS: The normalized 2(-ΔΔCt) of plasma TDRD7 mRNA based on ABL1 mRNA was 1.52 ± 0.63 in the case of the control group and 1.05 ± 0.34 in the case of the cataract patients, and the TDRD7 expression level of the cataract patients was lower than that of the control group (p = 0.048). The comparison of the genetic values of different types of cataracts demonstrated that the TDRD7 expression level of the cortical type and mixed type were lower than those of the nuclear type and posterior subcapsular opacity type (p = 0.017). CONCLUSIONS: Human cataracts and the TDRD7 gene loss-of-function mutations are strongly causally related, as the expression level of plasma TDRD7 mRNA in patients with cataracts was statistically significantly lower than in the normal control group.

Mechanisms of apoptosis on human lens epithelium after ultraviolet light exposure.

PURPOSE: The purpose of this study is to understand the mechanism of apoptosis occurring on a cultured human lens epithelial cell line after exposure to ultraviolet (UV) light. We intended to confirm the presence of cellular toxicity and apoptosis and to reveal the roles of p53, caspase 3 and NOXA in these processes. METHODS: Cells were irradiated with an ultraviolet lamp. Cellular toxicity was measured by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Hoechst staining and fluorescent anti-caspase 3 antibodies were used for apoptosis investigation. The quantities of p53, caspase 3, and NOXA were measured by Western blotting for to investigate the apoptosis pathway. RESULTS: Cellular toxicity on the human lens epithelium markedly increased with time after UV exposure. On Hoechst staining, we found that apoptosis also remarkably increased after exposure to ultraviolet light, compared with a control group. In the immunochemical study using anti-caspase 3 antibodies, active caspase 3 significantly increased after exposure to ultraviolet light. On Western blotting, p53 decreased, while caspase 3 and NOXA increased. CONCLUSIONS: Exposure of cultured human lens epithelial cell lines to ultraviolet light induces apoptosis, which promotes the expression of NOXA and caspase 3 increases without increasing p53. This may suggest that UV induced apoptosis is caused by a p53-independent pathway in human lens epithelial cells.

Clinical outcomes of epi-LASIK: 1-year results of on- and off-flap procedures with and without mitomycin-C.

AIM To evaluate and compare the clinical outcomes of epi-laser in situ keratomileusis (LASIK) performed either on-flap or off-flap with or without 0.02% mitomycin-C (MMC) in terms of corneal haziness, pain scores and satisfaction scores. METHODS In this non-randomised comparative retrospective study, the charts of 198 patients (394 eyes) who had undergone an epi-LASIK procedure for myopia (-1.5 D to -8.0 D spherical equivalent) correction were reviewed. Patients were classified into four groups: Group I, on-flap without MMC, 181 eyes; Group II, on-flap with MMC, 52 eyes; Group III, off-flap without MMC, 93 eyes; Group IV, off-flap with MMC, 68 eyes. We compared the group outcomes on the first day, 1, 3 and 6 months and 1 year after the operation. RESULTS The mean uncorrected visual acuity was significantly better in the off-flap groups (III and IV) than in the on-flap groups (I and II) on day 1 (p=0.002). There was no significant difference in the spherical equivalent among all groups at 1 year (p=0.305). Some degree of haziness was present in 10 eyes (Grade II: 2; Grade I: 8), but the haziness level was not significantly different among groups at 1 year (p=0.533). Pain scores (0-10) were lower in the off-flap groups (III and IV) (p=0.010). Satisfaction scores (0-10) were higher in the off-flap groups (III and IV), but the difference was not statistically significant (p=0.248). CONCLUSIONS Myopic correction by epi-LASIK surgery with all four methods showed stable visual results in terms of the 1-year postoperative clinical outcomes. Haziness levels revealed that treatment with 0.02% MMC was less effective than expected. Overall, the off-flap method offered faster visual recovery and less postoperative pain than the on-flap method.