Usability of the SB11 Pre-filled Syringe (PFS) in Patients with Retinal Diseases.

INTRODUCTION: SB11 (Byooviz™; Samsung Bioepis Co., Ltd.) is a ranibizumab (Lucentis®; Genentech, Inc.) biosimilar targeting vascular endothelial growth factor A for the treatment of retinal diseases. The pre-filled syringe (PFS) presentation of SB11 offers an alternative administration method to the vial, with the potential for enhanced safety and efficient syringe preparation. The objective of this study was to assess the ability of healthcare professionals (HCPs) to follow the instructions for use to prepare and administer SB11 PFS intravitreal (IVT) injections to patients with neovascular age-related macular degeneration (nAMD) or macular edema secondary to retinal vein occlusion (RVO). METHODS: This study was an open-label, single-arm, single-dose clinical study to evaluate the usability of the SB11 PFS in patients with nAMD or macular edema secondary to RVO. Four HCPs prepared and administered 0.5 mg SB11 PFS IVT injections to 34 patients. Product use task completion (12 tasks in total) was assessed by independent observers. Safety was assessed up to 7 days after injection of the investigational product. RESULTS: A total of 34 patients were enrolled and completed the study. All 12 tasks were successfully completed in 34 (100%) patients without a use-related failure. Most patients (32 patients, 94.1%) experienced no adverse events (AEs), whereas 2 (5.9%) patients experienced three treatment-emergent AEs (TEAEs) which were mild to moderate in severity. There were no severe or serious TEAEs reported during the study. CONCLUSIONS: This study showed that HCPs were able to successfully prepare and administer the SB11 PFS via IVT injection. No unexpected safety issues were identified. The SB11 PFS is a promising alternative for therapeutic administration of SB11 in patients with retinal disease. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT06176963; EudraCT number 2021-003566-12.

Effective intravitreal gene delivery to retinal pigment epithelium with hyaluronic acid nanospheres.

Inherited retinal degeneration (IRD) can cause a wide range of different forms of vision loss and blindness, and in spite of extensive advancements in gene therapy research, therapeutic approaches for targeting IRDs are still lacking. We have recently developed an approach for the intravitreal co-delivery of hyaluronic-acid nanospheres (HA-NSs) with sulfotyrosine (ST), effectively reaching the outer retina from the vitreal cavity. Here, our goal was to understand whether DNA-filled HA-NSs could generate gene expression in the outer retina. TxRed-labeled HA-NSs were compacted with plasmid DNA carrying a GFP reporter gene and intravitreally injected into the mouse retina. Follow-up at 4 weeks showed widespread gene expression in the outer retina and reduced, albeit present, expression at 8 weeks post-injection. Further analysis revealed this expression to be largely localized to the retinal pigment epithelium (RPE). These data show that intravitreal delivery of HA-NSs is a promising non-viral platform for the delivery of therapeutic genes and can generate pan-tissue, persistent gene expression in the RPE.

Acute Noninfectious Anterior Ocular Inflammation Following Ranibizumab Biosimilar Intravitreal Injection in a Patient With Recent COVID-19 Vaccination.

Even in the post-coronavirus disease 2019 (COVID-19) era, it is prudent to exercise caution regarding the timing between intravitreal anti-vascular endothelial growth factor (VEGF) injections and COVID-19 vaccinations, as ocular inflammation can occur following both procedures. However, this perspective has not been sufficiently discussed thus far. Herein, we report a case of acute noninfectious anterior ocular inflammation following an intravitreal injection of ranibizumab biosimilar (RBZ BS, Senju Pharmaceuticals, Japan) in a patient recently vaccinated against COVID-19. A 74-year-old male with myopic choroidal neovascularization (CNV) in the left eye was treated with RBZ BS intravitreal injection. He received his fourth COVID-19 vaccination with messenger ribonucleic acid (mRNA)-1273 (Moderna) two days prior to his second RBZ BS intravitreal injection. He reported no systemic symptoms associated with the fourth COVID-19 vaccination. The second RBZ BS intravitreal injection was safely performed without complications. However, a few hours later, he experienced blurred vision without ocular pain in his left eye, a symptom not observed after the first injection. He visited a local ophthalmologic clinic the following day and was subsequently referred to our hospital due to anterior ocular inflammation in the left eye. His vision in the left eye was 0.3 decimal best-corrected visual acuity. Examination revealed non-granulomatous anterior ocular inflammation with 3+ cells and 2+ flare in the left eye. Anterior vitreous inflammation, keratic precipitates, or conjunctivitis was absent. Fundus examination also showed no signs of posterior inflammation. Both fluorescence angiography and indocyanine green angiography revealed staining corresponding to CNV without retinal vasculature leakage. There is nothing abnormal with the right eye based on the examination. Given that the noninfectious ocular inflammation was likely, based on the acute onset of symptoms within less than 24 hours following the RBZ BS intravitreal injection, and the presence of non-granulomatous inflammation only in the anterior segment without ocular pain, betamethasone eye drops four times daily was initiated in the left eye on the first day following the second RBZ BS intravitreal injection. Then, his ocular inflammation improved to mild by the fourth day post-injection. His eye eventually cleared, with no cells or flare in the anterior chamber at five months. Eventually, given the clinical course of good response to only topical steroid therapy, the diagnosis of noninfectious anterior ocular inflammation following RBZ BS in the case of a recent episode of COVID-19 vaccination was retrospectively confirmed. Although this case represents one of the initial instances of noninfectious ocular inflammation following RBZ BS (Senju Pharmaceuticals) administration, sterile ocular inflammation after other intravitreal anti-VEGF therapy has already been well-reported. In addition, given the recent COVID-19 vaccination, the ocular inflammation might be influenced by the vaccination, synergistically leading to vaccine-associated uveitis with similar signs and symptoms. In conclusion, to prevent such a complex situation, it is advisable to consider an adequate interval between COVID-19 vaccination and intravitreal anti-VEGF injections.

The impact of music on anxiety, pain, and blood pressure in ophthalmic surgery: A systematic review and meta-analysis.

OBJECTIVES: To evaluate the effectiveness of music therapy in reducing anxiety, pain, and vital sign changes in ophthalmic surgery patients. METHODS: An extensive search of databases, including PubMed, Embase, Cochrane, Web of Science, and Google Scholar, identified relevant studies up to Jan 2024. Selection of studies was conducted based on the PICOS criteria. The quality of methodology was assessed using the Cochrane risk-of-bias assessment tool and Review Manager 5.4. Meta-analysis comparing the control group and the music therapy group was performed using R and Stata/SE 15.1 random or fixed effects model. RESULTS: This meta-analysis included fifteen studies comprising 2098 participants. The analysis revealed that music therapy significantly reduced the risk of high anxiety levels as measured by Visual Analogue Scale (VAS) (I2 = 0 %, RR(95 %CI): 0.75(0.63, 0.88), p = 0.0006), indicating a substantial effect without heterogeneity. The Anxiety scores determined by State-Trait Anxiety Inventory-State (STAI-S) also showed a significant decrease (SMD(95 %CI): -0.75(-0.88, -0.61), p < 0.0001), albeit with moderate heterogeneity (I² = 36 %). Additionally, music therapy was associated with a reduction in intraoperative pain levels, with no observed heterogeneity (I2 = 0 %, SMD(95 %CI): -0.74(-0.93, -0.56), p < 0.0001). In contrast, music intervention did not significantly influence self-reported nervousness, relaxation, or satisfaction levels as determined by VAS. Regarding to physiological parameters, a marginal decrease in systolic blood pressure (SBP) was observed (SMD(95 %CI): -0.42(-0.79, -0.04), p = 0.0286), with considerable heterogeneity (I² = 92 %). Diastolic blood pressure (DBP) experienced a slight reduction (I² = 90 %, SMD(95 %CI): -0.45(-0.79, -0.11), p = 0.0088). However, no significant effect was observed on patients' heart rate (p = 0.0864). CONCLUSION: Music therapy effectively reduced anxiety and pain, and moderately improved vital signs in patients undergoing ophthalmic surgery, highlighting its role in enhancing patient well-being. Further in-depth RCTs are needed to confirm its efficacy.

Efficacy of anti-VEGF intravitreal injection in traumatic submacular hemorrhage: a retrospective study.

OBJECTIVE: In this study we investigated the efficacy of short-term intravitreal injections of anti-vascular endothelial growth factors (anti-VEGF) in treating traumatic submacular hemorrhage. METHODS: A total of 115 patients were diagnosed with submacular hemorrhage between 2018 and 2022 at Shenzhen Eye Hospital. In a retrospective analysis, we examined 13 of these patients who presented with submacular hemorrhage and choroidal rupture due to ocular trauma. Eight patients were treated with intravitreal anti-VEGF injection and 5 with oral drugs. We systematically analyzed changes in their ocular conditions pre and post-treatment. The evaluations encompassed best-corrected visual acuity (BCVA), optical coherence tomography, fundus fluorescein angiography, and retinal imaging. RESULTS: The 13 patients diagnosed with submacular hemorrhage comprised of 10 males and 3 female, with their age ranging between 27 and 64 years, with an average age of 38.1 years (standard deviation [SD]: 11.27). A statistically significant reduction in central foveal thickness (CFT) was observed following intravitreal injections of anti-VEGF drugs (P = 0.03). In control group, the CFT was reduced without statistical significance (P = 0.10). The BCVA of the patients in treatment group improved significantly from 1.15 (SD: 0.62. Range: 0.4-2) to 0.63 (SD: 0.59. Range: 0.1-1.6), indicating an average increase of 4.13 lines (SD: 3.36. Range: 0-9) as measured by the visual acuity test using an eye chart (P = 0.01). The difference between baseline visual acuity and final visual acuity was not statistically significant in control group (P = 0.51). CONCLUSION: Short-term administration of anti-VEGF drugs exhibited significant efficacy in reducing submacular hemorrhage following ocular trauma and enhancing visual acuity.

Phase 1 Study of JNJ-81201887 Gene Therapy in Geographic Atrophy Secondary to Age-related Macular Degeneration.

OBJECTIVE: To evaluate the safety and tolerability of a single intravitreal injection of JNJ-81201887 (JNJ-1887) in patients with geographic atrophy (GA) secondary to advanced dry age-related macular degeneration (AMD). DESIGN: Phase 1, open-label, single-center, first-in-human clinical study. SUBJECTS: Adult patients (aged ≥50 years) with GA secondary to AMD in the study-treated eye (treated eye) with a best corrected visual acuity (BCVA) Snellen equivalent of 20/200 or worse in the treated eye (20/80 or worse after the first 3 patients), a total GA lesion size between 5 and 20 mm2 (2-8 disc area), and BCVA of 20/800 or better in fellow, non-treated eye were included. METHODS: Patients (N=17) were sequentially enrolled into low (3.56×1010 viral genome [vg]/eye; n=3), intermediate (1.07×1011 vg/eye; n=3), and high (3.56×1011 vg/eye; n=11) dose cohorts without steroid prophylaxis and assessed for safety and tolerability over 24 months. MAIN OUTCOME MEASURES: Safety and tolerability outcomes included assessment of ocular and non-ocular treatment-emergent adverse events (AEs) over 24 months. Secondary outcomes included GA lesion size and growth rate. RESULTS: Baseline patient characteristics were consistent with the disease under study, and all enrolled patients had foveal center-involved GA. JNJ-1887 was well tolerated across all cohorts, with no dose-limiting AEs. There were no serious or systemic AEs related to study intervention. Overall, 5/17 (29%) patients experienced 6 events of mild ocular inflammation related to study treatment; exam findings in all resolved, and AEs resolved in 4 of 5 patients following topical steroids or observation. One unresolved vitritis event, managed with observation, occurred in a patient with an unrelated fatal AE. No endophthalmitis or new-onset choroidal neovascularization was reported. GA lesion growth rate was similar among all cohorts over 24 months. For treated eyes in the high-dose cohort, GA lesion growth rate showed continued decline through 24 months, with a reduction in mean square root lesion growth from 0.211 mm at months 0-6 to 0.056 mm at months 18-24. CONCLUSIONS: All 3 studied doses of JNJ-1887 had a manageable safety profile through 24 months of follow-up. Further investigation of JNJ-1887 for the treatment of GA is warranted.

Endogenous Endophthalmitis: A 10-Year Review of Cases on the East Coast of Malaysia.

Purpose Our study aimed to describe the clinical profile of endogenous endophthalmitis, focusing on patient demographics, infection sources, microbial profiles, clinical outcomes, and factors affecting the final visual outcome. Methods A retrospective review was performed on data from 68 eyes of 60 patients diagnosed with endogenous endophthalmitis and hospitalized in two tertiary hospitals on the East Coast of Peninsular Malaysia from January 2011 to December 2020. The analysis encompassed evaluating patient age, gender, laterality, risk factors, infection origins, presenting and final visual acuity, microbial results, treatment responses, and factors affecting final visual outcomes. Results The average age of the patient cohort was 54.9 ± 13.3 years. Females were more likely to have endogenous endophthalmitis than males (33, 55.0% vs. 27, 45.0%). Twenty-seven patients (45.0%) presented with endogenous endophthalmitis in the left eye, while 25 patients (41.7%) had it in the right eye, and eight patients (13.3%) had bilateral involvement. Most patients had underlying predisposing conditions, predominantly diabetes mellitus (53, 88.3%). Infection sources were identified in 42 patients (70.0%), out of which urinary tract infections account for the majority (11, 18.3%). Klebsiella species(14, 22.7%) were the leading pathogens and were significantly associated with liver abscess cases. In this series, the majority of patients had poor presenting and final visual acuity of worse than 3/60 (56, 82.4% and 53, 77.9%, respectively). Thirty-six eyes (52.9%) underwent vitrectomy, resulting in only four eyes (11.11%) achieving final visual acuity better than 6/12. Presenting visual acuity was identified as the factor contributing to the blind final visual outcome (r = 0.707, p < 0.001). Conclusion Females were found to be more commonly affected by endogenous endophthalmitis than males. Klebsiella species were the most commonly isolated microorganisms and were typically associated with liver abscesses. Urinary tract infection was the most common predisposing factor. A majority of the patients had poor presenting and final visual acuity, in which poor visual acuity is a significant indicator of blind visual outcomes.

The effect of intravitreal cidofovir injection on end-stage glaucoma in dogs: a retrospective study of 153 eyes.

OBJECTIVE: To evaluate the long-term efficacy, prognostic factors, and complications of intravitreal cidofovir injection in dogs with end-stage glaucoma. ANIMALS: 130 client-owned dogs. METHODS: Medical records of dogs that underwent intravitreal cidofovir injections were reviewed. A minimum follow-up period of 6 months was required as the inclusion criterion. Signalment, type of glaucoma, preinjection intraocular pressure (IOP), types of applied glaucoma eye drop, coexisting ocular diseases, outcomes, and complications were recorded. Success was defined as IOP of ≤ 25 mm Hg at the 2-week recheck that remained to the 6-month recheck. RESULTS: The overall success rate of intravitreal cidofovir injection was 91.5% (140/153). The success rate of a single injection was 69.3% (106/153), of a second injection was 59.5% (25/42), of a third injection was 42.9% (6/14), of a fourth injection was 33.3% (2/6), and of a fifth injection was 50.0% (1/2). Intraocular pressures at 6 months after injection were relatively higher when the injection was repeated, fewer types of glaucoma eye drop were applied prior to the injection, and cataract stages were advanced at the time of injection (P < .05). The most common complications were phthisis bulbi (42.5%), cataract progression (30.1%), and intraocular hemorrhage (16.3%). Six eyes were enucleated, and 3 were enucleated due to corneal perforation. CLINICAL RELEVANCE: Intravitreal cidofovir injection had a high long-term success rate in lowering IOP in dogs with end-stage glaucoma.

Background diseases and the number of previous intravitreal aflibercept injections on immediate intraocular pressure increase and vitreous reflux rate in phakic eyes.

AIM: To evaluate the effect of background diseases and number of previous intravitreal aflibercept injections (IVAIs) on immediate intraocular pressure (IOP) increase and vitreous reflux (VR) rate and to evaluate the correlation of both age and axial length with immediate IOP increase and VR rate. METHODS: This study included 105 patients with cystoid macular edema secondary to retinal vein occlusion, 35 patients with diabetic macular edema, 69 patients with neovascular age-related macular degeneration (nAMD), and 12 patients with myopic choroidal neovascularization, which underwent first-time IVAI. The correlation of immediate IOP increase and VR rates with the four background diseases was investigated. Moreover, the correlation of age with immediate IOP increase and VR rate as well as correlation of axial length with immediate IOP increase and VR rate were evaluated. Further, 54 patients with nAMD were treated with IVAI>10 times (multiple IVAIs). Moreover, the correlation of immediate IOP increase and VR rates with first-time and multiple IVAIs in nAMD was determined. RESULTS: The immediate IOP increase (P=0.16) and VR rates (P=0.50) were almost similar among the four background diseases. The immediate postinjection IOP and age, VR rate and age, immediate postinjection IOP and axial length, or VR rate and axial length were not correlated in the four background diseases. The immediate IOP increase (P=0.66) and VR rates (P=0.28) did not significantly differ between first-time and multiple IVAIs in nAMD. CONCLUSION: Background diseases and number of previous IVAIs have no effect on immediate IOP increase and VR rate. Further, age and axial length have no correlation on immediate IOP increase and VR rate.

[Changes in intraocular pressure and biometric parameters of the anterior segment of the eye after intravitreal injections]. / Izmeneniya urovnya vnutriglaznogo davleniya i biometricheskikh pokazatelei perednego segmenta glaza posle intravitreal'nykh in"ektsii.

PURPOSE: This study compares the changes in the parameters of the anterior chamber of the eye using anterior segment optical coherence tomography (AS-OCT) in patients with a natural and artificial lens after treatment of neovascular age-related macular degeneration (nAMD) by multiple intravitreal injections (IVI) of anti-VEGF drugs. MATERIAL AND METHODS: The patients were divided into 2 groups: group 1 (control) included 30 patients (30 eyes) with a natural lens, group 2 - 30 patients (30 eyes) with an intraocular lens (IOL). AS-OCT was performed using the Revo NX tomograph (Optopol, Poland) to analyze anterior chamber depth (ACD) and the parameters of anterior chamber angle (ACA). Intraocular pressure (IOP) was measured with a contact tonometer ICare Pro. RESULTS: In patients with an IOL, the IOP level 1 minute after intravitreal injection (IVI) of an anti-VEGF drug was statistically lower than in the control group, on average by 17.8% during the first IVI and by 28.7% after 1 year of observation (p<0.001). ACD before treatment was statistically significantly higher in patients with IOL compared to patients of group 1 by an average of 39.3% (p<0.001). ACA from the nasal and temporal sides in the meridian 0°-180° before the start of treatment was statistically significantly wider in phakic patients than in the control group, by an average of 15.9±9.3° (p<0.001) and 16.9±8.2° (p<0.001), respectively. According to AS-OCT, there was no shift of the iris-lens diaphragm in patients with an IOL after multiple IVI of an anti-VEGF drug, in contrast to the control group. CONCLUSIONS: AS-OCT was used to determine for the first time the changes in the parameters of the anterior chamber of the eye in patients with a natural and artificial lens after multiple injections of an anti-VEGF drug in the treatment of nAMD.

Activation of Shh/Smo is sufficient to maintain oligodendrocyte precursor cells in an undifferentiated state and is not necessary for myelin formation and (re)myelination.

Myelination is the terminal step in a complex and precisely timed program that orchestrates the proliferation, migration and differentiation of oligodendroglial cells. It is thought that Sonic Hedgehog (Shh) acting on Smoothened (Smo) participates in regulating this process, but that these effects are highly context dependent. Here, we investigate oligodendroglial development and remyelination from three specific transgenic lines: NG2-CreERT2 (control), Smofl/fl/NG2-CreERT2 (loss of function), and SmoM2/NG2-CreERT2 (gain of function), as well as pharmacological manipulation that enhance or inhibit the Smo pathway (Smoothened Agonist (SAG) or cyclopamine treatment, respectively). To explore the effects of Shh/Smo on differentiation and myelination in vivo, we developed a highly quantifiable model by transplanting oligodendrocyte precursor cells (OPCs) in the retina. We find that myelination is greatly enhanced upon cyclopamine treatment and hypothesize that Shh/Smo could promote OPC proliferation to subsequently inhibit differentiation. Consistent with this hypothesis, we find that the genetic activation of Smo significantly increased numbers of OPCs and decreased oligodendrocyte differentiation when we examined the corpus callosum during development and after cuprizone demyelination and remyelination. However, upon loss of function with the conditional ablation of Smo, myelination in the same scenarios are unchanged. Taken together, our present findings suggest that the Shh pathway is sufficient to maintain OPCs in an undifferentiated state, but is not necessary for myelination and remyelination.

The differential effects of blocking retinal orexin receptors on the expression of retinal c-fos and hypothalamic Vip, PACAP, Bmal1, and c-fos in Male Wistar Rats.

Orexin A and B (OXA and OXB) and their receptors are expressed in the majority of retinal neurons in humans, rats, and mice. Orexins modulate signal transmission between the different layers of the retina. The suprachiasmatic nucleus (SCN) and the retina are central and peripheral components of the body's biological clocks; respectively. The SCN receives photic information from the retina through the retinohypothalamic tract (RHT) to synchronize bodily functions with environmental changes. In present study, we aimed to investigate the impact of inhibiting retinal orexin receptors on the expression of retinal Bmal1 and c-fos, as well as hypothalamic c-fos, Bmal1, Vip, and PACAP at four different time-points (Zeitgeber time; ZT 3, 6, 11, and ZT-0). The intravitreal injection (IVI) of OX1R antagonist (SB-334867) and OX2R antagonist (JNJ-10397049) significantly up-regulated c-fos expression in the retina. Additionally, compared to the control group, the combined injection of SB-334867 and JNJ-10397049 showed a greater increase in retinal expression of this gene. Moreover, the expression of hypothalamic Vip and PACAP was significantly up-regulated in both the SB-334867 and JNJ-10397049 groups. In contrast, the expression of Bmal1 was down-regulated. Furthermore, the expression of hypothalamic c-fos was down-regulated in all groups treated with SB-334867 and JNJ-10397049. Additionally, the study demonstrated that blocking these receptors in the retina resulted in alterations in circadian rhythm parameters such as mesor, amplitude, and acrophase. Finally, it affected the phase of gene expression rhythms in both the retina and hypothalamus, as identified through cosinor analysis and the zero-amplitude test. This study represents the initial exploration of how retinal orexin receptors influence expression of rhythmic genes in the retina and hypothalamus. These findings could provide new insights into how the retina regulates the circadian rhythm in both regions and illuminate the role of the orexinergic system expression within the retina.

[Translated article] Syringes for intraocular administration: A systematic review.

OBJECTIVE: The off-label use in clinical practice of non-approved syringes for intravitreal drug administration has resulted in the detection of silicone oil drops in the vitreous of some patients. This situation derives from the lack of approved syringes for intraocular use in the Spanish market. The aim of this work is to review the use of syringes for intraocular administration, as well as to search for alternatives that meet the legal requirements for these unmet needs. METHOD: A systematic review was performed following the PRISMA 2020 guidelines by searching PubMed with the descriptors: (silicone) AND (syringes) AND ((intraocular) OR (intravitreal)) and filtering all existing publications from January 2006 to December 2023, including all those articles dealing with silicone oil release in intravitreal injections and analysing the possible consequences. RESULTS: Sixty-eight results were found, 23 of which were excluded because they did not deal with the subject under study, leaving a total of 45 articles for the systematic review. These were classified according to the conclusions obtained in 4 groups: the adverse reactions produced by silicone; the administration technique; the physicochemical aspects of silicone release; and the characteristics of the medical device. After reviewing the current manufacturers and technical data sheets of commercialised syringes, the existing syringes for this use have been collected, finding 2 that will probably be commercialised in Spain at the beginning of 2024: Zero Residual™ 0.2 ml SiO-free and VitreJect® Ophthalmic. CONCLUSIONS: From the results obtained, it can be interpreted that the use of syringes and needles with silicone for intravitreal use is a concern for health professionals due to the implications and consequences that may arise in patients, the most important being adverse reactions, so it is necessary to have silicone-free syringes on the market that are specific for intraocular use. Safety and legality in the use of intraocular syringes and needles is essential to guarantee ocular integrity and patient health.

Treatment Effects of Switching to Faricimab in Eyes with Diabetic Macular Edema Refractory to Aflibercept.

Background and Objectives: Faricimab is a vascular endothelial growth factor A and angiopoietin-2 bispecific antibody. It is a novel therapeutic approach distinct from previous anti-vascular endothelial growth factor agents. This study aimed to evaluate the efficacy of switching from aflibercept to faricimab in the treatment of diabetic macular edema (DME) refractory to aflibercept, with a specific focus on the resolution of macular edema. Materials and Methods: The medical records of 29 eyes of 21 patients with DME that were refractory to intravitreal injections of aflibercept (IVAs) and who had completed the clinical follow-up of at least four intravitreal injections of faricimab (IVFs) were reviewed. The central retinal thickness (CRT), best-corrected visual acuity (BCVA), and the mean period (weeks) until the next injection were measured after the second-to-last IVA, first-to-last IVA, last IVA, and first to fourth IVFs following the transition to IVF. Results: The mean time from the first IVF to the assessment of effectiveness was significantly shorter than the time to the last IVA; however, no significant difference was found in the time from the second, third, and fourth IVFs to the assessment. The mean CRTs after the first and second IVFs were not significantly different from the CRT after the last IVA, but the mean CRT after the third and fourth IVFs was significantly thinner than that after the last IVA (p = 0.0025 and p = 0.0076, respectively). The mean BCVAs after the third and fourth IVFs significantly improved compared with that after the last IVA (p = 0.0050 and p = 0.0052, respectively). Conclusions: When switching the treatment to IVF for eyes with IVA-resistant DME, better treatment outcomes are achieved if IVF is performed three or more times.

[Topical application of hypotensive drugs for the prevention of intraocular pressure elevation after intravitreal injections of anti-VEGF drugs]. / Mestnoe primenenie gipotenzivnykh preparatov s tsel'yu profilaktiki povysheniya urovnya vnutriglaznogo davleniya posle intravitreal'nykh in"ektsii anti-VEGF-preparatov.

The management protocol for patients with neovascular age-related macular degeneration (nAMD) involves multiple intravitreal injections (IVI) of anti-VEGF drugs. The ability to reduce the peak intraocular pressure (IOP) rise is greatly important in clinical practice. PURPOSE: This study evaluates the effect of topical hypotensive drugs on the short-term IOP rise after IVI of anti-VEGF drugs in patients with nAMD. MATERIAL AND METHODS: The prospective study included 80 patients with newly diagnosed nAMD. Before the start of treatment, the patients were divided into 4 groups of 20 people each: 1st - controls, who received no prophylactic drugs, in the 2nd, 3rd and 4th groups local instillations of one drop of hypotensive drugs brinzolamide 1%, brinzolamide-timolol, brimonidine-timolol were performed in the conjunctival sac twice: 1 day before the injection (at 20:00) and on the day of the injection 2 hours before the manipulation (at 08:00), respectively. IOP was measured in each patient using ICare Pro non-contact tonometer before injection, as well as 1 min, 30 and 60 min after injection. RESULTS: Prophylactic use of hypotensive drugs was associated with a significant decrease in IOP immediately after IVI compared to the same parameter in the 1st group (p<0.001), the maximum decrease in IOP values was observed when using a fixed combination of brimonidine-timolol by 12.1 mm Hg compared to the controls (p<0.001), the combination of brinzolamide-timolol reduced IOP by 8.5 mm Hg (p<0.001), brinzolamide 1% led to the smallest decrease in IOP - by 5.1 mm Hg (p<0.001). CONCLUSION: Study patients that received instillations of brimonidine-timolol combination of one drop into the conjunctival sac 1 day before the injection and on the day of the injection showed the maximum decrease in IOP compared to patients of the other groups.

Glycemic Control in Patients After Initiation of Treatment for Vision-Threatening Diabetic Retinopathy.

Purpose: To understand changes in glycemic control in patients being managed with vision-threatening diabetic retinopathy (DR). Methods: A retrospective cohort study was performed of patients with type 2 diabetes mellitus who were at least 18 years old. Patients who started treatment for vision-threatening DR were matched with controls based on age, sex, race/ethnicity, duration of diabetes, history of diabetes, and history of hypertension. The primary outcome was the difference in hemoglobin A1c (HbA1c) change after 12 months between cases and controls. Results: Four hundred fifty patients were included (225 cases paired with 225 controls); 58.7% of patients were men, and 33.8% were Hispanic. The mean (±SD) baseline HbA1c was 8.12% ± 1.57%. Patients receiving retinal interventions did not experience a significant change in HbA1c compared with controls 12 months after starting treatment (0.11% ± 1.51% vs -0.02% ± 1.52%; P = .31). In addition, there was not a significant difference in HbA1c change between cases and controls when considering the number of interventions: 2 or fewer interventions (+0.08% ± 1.30% vs -0.07% ± 1.15%; P = .46), 3 to 6 interventions (+0.41% ± 1.71% vs +0.01% ± 2.0%; P = .08), and 7 or more interventions (-0.17% ± 1.49% vs 0.0% ± 1.31%; P = .50). Conclusions: Patients who received treatment for vision-threatening DR did not experience a change in HbA1c. Increasing number of retinal interventions also did not appear to impact glycemic control. There appears to be a missed opportunity for improving diabetes management in patients with vision-threatening DR.

Clinical features, management, and outcomes of patients with sterile endophthalmitis associated with intravitreal bevacizumab injection: retrospective case series.

PURPOSE: To evaluate clinical features, treatment protocol, outcomes, and complications that developed in this case series of 24 patients who had consecutive sterile endophthalmitis after intravitreal bevacizumab (IVB) injection. METHODS: In this retrospective case series, IVB was repackaged in individual aliquots from the three batches that were used on the same day. IVB was injected into 26 eyes of 26 patients due to diabetic macular edema, age-related macular degeneration, and branch retinal vein occlusion. All patients had intraocular inflammation. Patients were divided into two groups severe and moderate inflammation according to the intraocular inflammation. The medical records of all patients were reviewed. At each follow-up visit, the complete ophthalmologic examination was performed, including best corrected visual acuity (BCVA), intraocular pressure, biomicroscopy, and posterior fundus examination. RESULTS: Twenty-four of 26 patients were included in the study. Two patients were excluded from this study since they didn't come to follow-up visits. The mean BCVA was 1.00 ± 0.52 Log MAR units before IVB. At the final visit, the BCVA was 1.04 ± 0.47 Log MAR units. These differences were not significant (p = 0.58). Of the 24 eyes, 16 eyes had severe, and 8 eyes had moderate intraocular inflammation. Eleven eyes in the severe inflammation group underwent pars plana vitrectomy due to intense vitreous opacity. Smear, culture results, and polymerase chain reaction results were negative. CONCLUSION: Sterile endophthalmitis may occur after IVB injection. Differential diagnosis of sterile endophthalmitis from infective endophthalmitis is crucial to adjust the appropriate treatment and prevent long-term complications due to unnecessary treatment.

Real-World Weekly Efficacy Analysis of Faricimab in Patients with Age-Related Macular Degeneration.

Objectives: This study entailed a weekly analysis of real-world data (RWD) on the safety and efficacy of intravitreal (IVT) faricimab in neovascular age-related macular degeneration (nAMD). Methods: A retrospective, single-centre clinical trial was conducted at the Department of Ophthalmology, University Hospital Zurich, University of Zurich, Switzerland, approved by the Cantonal Ethics Committee of Zurich, Switzerland. Patients with nAMD were included. Data from patient charts and imaging were analysed. The safety and efficacy of the first faricimab injection were evaluated weekly until 4 weeks after injection. Results: Sixty-three eyes with a complete 4-week follow-up were enrolled. Six eyes were treatment-naïve; fifty-seven eyes were switched to faricimab from another treatment. Neither group showed signs of retinal vasculitis during the 4 weeks after injection. Central subfield thickness (CST) and volume (CSV) showed a statistically significant decrease compared to the baseline in the switched group (CST: p = 0.00383; CSV: p = 0.00702) after 4 weeks. The corrected visual acuity returned to the baseline level in both groups. The macular neovascularization area decreased in both groups, but this was not statistically significant. A complete resolution of sub- and intraretinal fluid after 4 weeks was found in 40% (switched) and 75% (naïve) of the treated patients. Conclusions: The weekly follow-ups reflect the structure-function relationship beginning with a fast functional improvement within two weeks after injection followed by a return to near-baseline levels after week 3. The first faricimab injection in our cohort showed a high safety profile and a statistically significant reduction in macular oedema in switched nAMD patients.