Efficacy and Safety of Biosimilar QL1207 vs. the Reference Aflibercept for Patients with Neovascular Age-Related Macular Degeneration: A Randomized Phase 3 Trial.

INTRODUCTION: This trial aimed to compare the efficacy and safety between biosimilar QL1207 and the reference aflibercept for the treatment of neovascular age-related macular degeneration (nAMD). METHODS: This randomized, double-blind, phase 3 trial was conducted at 35 centers in China. Patients aged ≥ 50 years old with untreated subfoveal choroidal neovascularization secondary to nAMD and best-corrected visual acuity (BCVA) letter score of 73-34 were eligible. Patients were randomly assigned to receive intravitreous injections of QL1207 or aflibercept 2 mg (0.05 ml) in the study eye every 4 weeks for the first 3 months, followed by 2 mg every 8 weeks until week 48, stratified by baseline BCVA ≥ or < 45 letters. The primary endpoint was BCVA change from baseline at week 12. The equivalence margin was ± 5 letters. The safety, immunogenicity, pharmacokinetics (PK), and plasma vascular endothelial growth factor (VEGF) concentration were also evaluated. RESULTS: A total of 366 patients were enrolled (QL1207 group, n = 185; aflibercept group, n = 181) from Aug 2019 to Jan 2022 with comparable baseline characteristics. The least-squares mean difference in BCVA changes was - 1.1 letters (95% confidence interval - 3.0 to 0.7; P = 0.2275) between the two groups, within the equivalence margin. The incidences of treatment-emergent adverse events (TEAE; QL1207: 71.4% [132/185] vs. aflibercept: 71.8% [130/181]) and serious TEAE (QL1207: 14.1% [26] vs. aflibercept: 12.7% [23]) appeared comparable between treatment groups, and no new safety signal was found. Anti-drug antibody, PK profiles, and VEGF concentration were similar between the two groups. CONCLUSIONS: QL1207 has equivalent efficacy to aflibercept for nAMD with similar safety profiles. It could be used as an alternative anti-VEGF agent for clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05345236 (retrospectively registered on April 25, 2022); National Medical Products Administration of China: CTR20190937 (May 20, 2019).

Safety profile of 0.0015% tafluprost eye drops in China: a post-marketing observational study.

AIM: To investigate the treatment pattern and safety of tafluprost for glaucoma and ocular hypertension (OH) in clinical practice in China. METHODS: This post-marketing observational study included patients who received tafluprost to lower intraocular pressure (IOP) within 30d between September 2017 and March 2020 in 20 hospitals in China. Adverse drug reactions (ADRs) during tafluprost treatment and within 30d after the treatment were collected. RESULTS: A total of 2544 patients were included in this study, of them 58.5% (1488/2544) had primary open angle glaucoma (POAG), 21.9% (556/2544) had OH and 19.7% (500/2544) used tafluprost for other reasons. Of 359 ADRs occurred in 10.1% (258/2544) patients, and no serious adverse event occurred. The most common ADR was conjunctival hyperemia (128 ADRs in 124 patients, 4.9%). Totally 1670 participants (65.6%) combined tafluprost with carbonic anhydrase inhibitors (CAIs; 37.1%, 620/1670), sympathomimetics (33.5%, 559/1670), ß-blockers (33.2%, 555/1670), other prostaglandin analogs (PGAs; 15.6%, 260/1670) and other eye drops (15.1%, 253/1670). The highest incidence of conjunctival hyperemia was noted in patients who received tafluprost in combination with other PGAs (23 ADRs in 23 patients, 8.8%, 23/260) and the lowest was in combination with CAIs (16 ADRs in 16 patients, 2.6%, 16/620). Tafluprost was applied in primary angle-closure glaucoma (41.6%, 208/500), after glaucoma surgery (17.8%, 89/500) and after non-glaucoma surgery (15.8%, 79/500). CONCLUSION: Tafluprost is safe for POAG and OH, and tolerable when combined with other eye drops and under various clinical circumstances.

Endovascular Hyaluronidase Application Through Superselective Angiography to Rescue Blindness Caused by Hyaluronic Acid Injection.

BACKGROUND: Blindness is a rare but catastrophic complication of facial hyaluronic acid (HA) injection. Although various means to rescue visual impairment have been employed, no consensus regarding effective treatment has yet been reached. We organized a multidisciplinary team to address this emergency situation by means of endovascular hyaluronidase application. OBJECTIVES: The aim of this study was to investigate the direct delivery of hyaluronidase to ophthalmic artery occlusion through endovascular cannulation to resolve HA-induced blindness. METHODS: Four patients with visual impairments caused by HA filler embolization were subjected to sequential treatments. Through superselective angiography, a microcatheter was introduced along a guidewire from the femoral artery to the ophthalmic artery to directly deliver hyaluronidase to the HA embolism. The safety and efficiency of this treatment were systematically analyzed. RESULTS: Selective cerebral angiography demonstrated that the endovascular application of hyaluronidase significantly alleviated occlusion in 3 patients. One patient showed slight visual improvement, whereas the other patients showed no improvement in their visual function during a follow-up period of more than 3 months. One patient suffered from cerebral infarction in the left middle cerebral artery during the intervention surgery. Moreover, 2 patients showed multiple lacunar cerebral infarctions after the operation, whereas none exhibited symptoms of hemiplegia during follow-up. CONCLUSIONS: Although the endovascular application of hyaluronidase could partially recanalize the occluded branches of the ophthalmic artery, it had limited effects on restoring vision. Considering the risks of vascular intervention surgery, this approach should be considered with caution.

Nerve growth factor promotes the proliferation of Müller cells co-cultured with internal limiting membrane by regulating cell cycle via Trk-A/PI3K/Akt pathway.

BACKGROUND: Nerve growth factor (NGF), produced by Müller cells, and internal limiting membrane (ILM) have fundamental roles in the development of full-thickness macular hole (FTMH). However, the potential crosstalk between NGF and ILM in FTMH is unclear. This study aimed to explore the mechanism and effects of NGF on the proliferation of Müller cells co-cultured with ILM. METHODS: Primary Müller cells and ILM from New Zealand rabbits were extracted and authenticated with specific staining. Müller cells co-cultured with or without ILM were exposed to NGF and then analysed. Müller cell viability was estimated using cell counting kit-8. Cell cycle analysis was performed by flow cytometry. The levels of cell cycle-related gene were detected using qRT-PCR. The TrK-A/Akt signal axis and downstream signaling cascades such as p21, CyclinE, CDK2, CyclinD1, and CDK4 were investigated by western blotting. RESULTS: ILM treatment alone induced the proliferation of Müller cells following the promotion of phosphorylated Akt, while growth of Müller cells was enhanced by activation of the Trk-A/Akt pathway under the stimulation of NGF or NGF + ILM. Additionally, the ratio of S-phase cells was increased, while G2-phase cells decreased upon the treatment with either ILM or NGF alone, or with NGF + ILM co-treatment. Cell cycle-related genes such as CyclinD1, CyclinE, CDK2, and CDK4 were all upregulated, but p21 expression was downregulated in the presence of NGF, ILM, or NGF + ILM. There was an additive effect on cell proliferation and cell cycle in the group of Müller cells exposed to NGF co-cultured with ILM compared with either NGF or ILM treatment alone. However, both K252ɑ (inhibitors of Trk-A) and LY294002 (inhibitor for Akt) counteracted the effect of NGF or NGF + ILM on the protein levels of Trk-A, Akt, CyclinD1, CyclinE, CDK2, and p21. CONCLUSIONS: Müller cells co-cultured with ILM or NGF promoted cell proliferation by regulating cell cycle-correlated proteins via the PI3K/Akt pathway. ILM + NGF further amplified the PI3K/Akt signaling pathway by binding to Trk-A, leading to more cell growth. This study provides new insight into the potential mechanism of NGF-mediated proliferation of Müller cells co-cultured with or without ILM, which may have considerable impact on therapies for FTMH.

Riboflavin and ultraviolet A irradiation for the prevention of progressive myopia in a guinea pig model.

In this study, we evaluated the effect of oral administration of riboflavin combined with whole-body ultraviolet A (UVA) irradiation on the biochemical and biomechanical properties of sclera in a guinea pig model to control the progression of myopia. Experimental groups were administered 0.1% riboflavin solution with or without vitamin C by gavage from 3 days before myopic modeling and during the modeling process. Guinea pigs underwent 30 min of whole-body UVA irradiation after each gavage for 2 weeks. For control groups, guinea pigs were administered vitamin C and underwent either whole-body UVA irradiation without 0.1% riboflavin solution or whole-body fluorescent lamp irradiation with or without 0.1% riboflavin solution. Resultantly, myopia models were established with an increased axial length and myopic diopter. Compared with myopic eyes in the control groups, the net increase in axial length, diopter and strain assessment decreased significantly, and the net decrease in sclera thickness, ultimate load, and stress assessment decreased significantly in experimental groups. MMP-2 expression showed a lower net increase, while TIMP-2 expression showed a lower net decrease. In addition, hyperplasia of scleral fibroblasts was more active in myopic eyes of experimental groups. Overall, our results showed that oral administration of riboflavin with whole-body UVA irradiation could increase the strength and stiffness of sclera by altering the biochemical and biomechanical properties, and decreases in axial elongation and myopic diopter are greater in the guinea pig myopic model.

Binocular indirect ophthalmo microscope-assistant gas-perfused pars plana vitrectomy: A novel technique for vitreous sample acquisition.

The vitreous sample has been used for the diagnosis of uveitis and intraocular malignancy for decades. The sample volume is usually limited to 1 mL with current techniques. In the present study, a novel technique for higher amount of vitreous sample acquisition, that is, Binocular Indirect Ophthalmo Microscope-assistant gas-perfused pars plana vitrectomy (BAG-PPV) was invented.For diagnostic purpose, BAG-PPV with 23-ga vitrectomy system was performed on a 54-year-old Chinese male with the symptom of bilateral atypical uveitis. More than 3 mL of vitreous sample per eye was collected without any significant complications. Cytopathology was confirmed on the basis of cell surface markers and released cytokines by flow cytometry analysis and cytokine assays respectively.A monoclonal B-cell population with the pattern of CD5, CD10, cyKi67, CD71, FMC7, CD23, and kappa light chain single expression for the right eye and a monoclonal B-cell pattern with CD5, CD10, cyKi67, and kappa light chain restriction for the left eye were identified. The cytokine assay revealed high levels of interleukin (IL)-10 (90,838.30 and 41,098.0 pg/mL for the right and left eyes, respectively) and IL10/IL6 ratios for both eyes (with 90.78 and 63.26 for the IL10/IL6 ratios of the right and left eyes, respectively), while those for the cerebrospinal fluid were low (4.77 pg/mL for the IL10 level and 0.65 for the IL10/IL6 ratio). Based on the results, the patient was diagnosed with primary intraocular lymphoma for bilateral eyes.Our results demonstrated that diagnostic vitrectomy with BAG-PPV using the 23-ga vitrectomy system was safe, efficient, and able to provide useful diagnostic information for suspicious intraocular malignancy and other atypical uveitis.

23-Gauge vitrectomy with external drainage therapy as a novel procedure to displace massive submacular hemorrhage secondary to polypoidal choroidal vasculopathy.

INTRODUCTION: Massive subretinal hemorrhage (SRH) due to polypoidal choroidal vasculopathy (PCV) remains a challenging field and the best treatment is still not certain. In the present study, we performed a novel surgical method which combined 23-gauge vitrectomy with external drainage therapy for displace massive SRH secondary to PCV. METHODS: From April 2015 to July 2015, 4 consecutive patients with massive SRH secondary to PCV received 23-gauge transconjunctival sutureless vitrectomy with external drainage therapy. Massive SRH was drained by scleral tunnel which was created using 30-gauge ultrathin needles during vitrectomy. We assessed the feasibility and safety of this procedure by analyzing best-corrected vision acuity (BCVA), central foveal thickness (CFT), and complication. RESULTS: Four patients had a mean age of 63.8 ±â€Š6.4 years (range: 59-73 years). The average interval between onset of symptoms of SRH and surgery was 23.8 ±â€Š11.1 days (range: 10-35 days). Mean follow-up duration was 7.0 ±â€Š0.8 months. All patients completed 6 months follow-up. Mean BCVA gradually improved during the follow-up period. At 6 months after treatment, mean BCVA was significantly improved in comparison to preoperative findings (P = 0.043, paired t test). One month after treatment, mean CFT was significantly thinner than baseline (P = 0.002, paired t test). No serious ocular or systemic adverse events were observed to be associated with combination of 23-gauge vitrectomy with external drainage therapy during the 6 months follow-up period. CONCLUSIONS: Our results show that a combination of 23-gauge vitrectomy with external drainage therapy is a novel effective and safe procedure that may be a good alternative for massive SRH due to PCV.

[Laparoscopic operations for benign ovarian cysts: report of 50 cases].

OBJECTIVE: To investigate the surgical indications and techniques of laparoscopic operation for benign ovarian cysts. METHODS: Fifty patients with benign ovarian cysts underwent laparoscopic operations of cyst decollement, ovariotomy and adnexectomy. RESULTS: There were 46 cases (92%) of decollement, 2 cases (4%) of adnexectomy and 3 cases (6%) of ovariotomy. The operation time was 30-120 min, and the intraoperative blood loss 20 ml. CONCLUSION: Laparoscopic operation of benign ovarian cysts has advantages of minimal invasive surgery.