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PurposeTo evaluate 2-year efficacy, durability, and safety of the bispecific antibody faricimab, which inhibits both angiopoietin-2 and VEGF-A.DesignTENAYA (ClinicalTrials.gov identifier, NCT03823287) and LUCERNE (ClinicalTrials.gov identifier, NCT03823300) were identically designed, randomized, double-masked, active comparator-controlled phase 3 noninferiority trials.ParticipantsTreatment-naive patients with neovascular age-related macular degeneration (nAMD) 50 years of age or older.MethodsPatients were randomized (1:1) to intravitreal faricimab 6.0 mg up to every 16 weeks (Q16W) or aflibercept 2.0 mg every 8 weeks (Q8W). Faricimab fixed dosing based on protocol-defined disease activity at weeks 20 and 24 up to week 60, followed up to week 108 by a treat-and-extend personalized treatment interval regimen.Main outcome measuresEfficacy analyses included change in best-corrected visual acuity (BCVA) from baseline at 2 years (averaged over weeks 104, 108, and 112) and proportion of patients receiving Q16W, every 12 weeks (Q12W), and Q8W dosing at week 112 in the intention-to-treat population. Safety analyses included ocular adverse events (AEs) in the study eye through study end at week 112.ResultsOf 1326 patients treated across TENAYA/LUCERNE, 1113 (83.9%) completed treatment (n = 555 faricimab; n = 558 aflibercept). The BCVA change from baseline at 2 years was comparable between faricimab and aflibercept groups in TENAYA (adjusted mean change, +3.7 letters [95% confidence interval (CI), +2.1 to +5.4] and +3.3 letters [95% CI, +1.7 to +4.9], respectively; mean difference, +0.4 letters [95% CI, -1.9 to +2.8]) and LUCERNE (adjusted mean change, +5.0 letters [95% CI, +3.4 to +6.6] and +5.2 letters [95% CI, +3.6 to +6.8], respectively; mean difference, -0.2 letters [95% CI, -2.4 to +2.1]). At week 112 in TENAYA and LUCERNE, 59.0% and 66.9%, respectively, achieved Q16W faricimab dosing, increasing from year 1, and 74.1% and 81.2%, achieved Q12W or longer dosing. Ocular AEs in the study eye were comparable between faricimab and aflibercept groups in TENAYA (55.0% and 56.5% of patients, respectively) and LUCERNE (52.9% and 47.5% of patients, respectively) through week 112.ConclusionsTreat-and-extend faricimab treatment based on nAMD disease activity maintained vision gains through year 2, with most patients achieving extended dosing intervals.Financial disclosure(s)Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

PurposeMethodsResultsConclusionTo assess the efficacy and safety of preoperative intravitreal triamcinolone acetonide (IVTA) combined with internal limiting membrane (ILM) peeling for idiopathic epiretinal membrane (IMEM).This was a retrospective study. Thirty-six phakic eyes of 35 patients were included in this study. IVTA was administered to 18 patients (18 eyes, Group IVTA) 7 days before vitrectomy, while the other 17 patients (18 eyes, Group no-IVTA) only underwent vitrectomy and ILM peeling. Patients were followed up for at least 6 months. Data on best-corrected visual acuity (BCVA), intraocular pressure (IOP), central macular thickness (CMT), inner retinal thickness (IRT), vascular parameters (measured by optical coherence tomography angiography, OCTA), mean macular sensitivity (MMS), 63% bivariate contour ellipse area (BCEA) and P1 (measured by macular integrity assessment, MAIA) were collected.There were significant differences in BCVA and IRT between the IVTA group and the no-IVTA group at 6 months after surgery (p = .000 and p = .010). The CMT and MMS of the two groups significantly changed from the preoperative values; however, there were no differences between the 2 groups during the entire study period (p = .242 and p = .849). The changes in vascular parameters, including foveal avascular zone (FAZ) area and vessel densities of superficial and deep capillary plexus (SCP VD and DCP VD), in the two groups were not statistically significant. There were no statistically significant differences in 63% BCEA and P1 either.Macular morphology and macular integrity improved after vitrectomy combined with ILM peeling surgery. Compared with the no-IVTA group, preoperative intravitreal triamcinolone acetonide can improve best corrected visual acuity and accelerate the absorption of intraretinal fluid in terms of a significant reduction in IRT. [ABSTRACT FROM AUTHOR]

To elucidate the contributions of M-cone to the negative off-response of rat Electroretinogram (ERG) using specific drugs and spontaneous mutation rat models. The ON/OFF responses of ERG were evoked by long duration flash (200 ms) pre or post the application of 2-amino-4-phosphonobutyric acid (APB), cis-piperidine-2,3-dicarboxylic acid (PDA) or BaCl2 to the Sprague-Dawley (SD) rats. Furthermore, the ON/OFF responses of other two types of mutation rats, the middle-wavelength opsin cone dysfunction (MCD) rats and congenital stationary night blindness (CSNB) rats, were recorded. Typical scotopic and photopic ON/OFF responses were recorded in SD rats. At light offset, the OFF response showed a rapid negative deflection, then the retinal potential slowly returned to baseline from the trough of the negative off-response. The negative off-response was completely eliminated by the intravitreal injection of 400 µM APB. The amplitude of the negative off-response was reduced by the application of 5 mM PDA. However, the off component was not blocked by the application of 50 µM BaCl2. In addition, distinct differences of OFF response were found among MCD, CSNB and SD rats. The scotopic ON/OFF ERG of the MCD and CSNB rats showed no obvious negative off component at light offset, while the negative off component of photopic ON/OFF ERG was found in the CSNB rats, though with lower amplitude. The negative off-response of rat ERGs is not the off component of M-wave: a negative potential change at stimulus onset or offset. M-cone and the depolarizing bipolar cell play a central role in the signal transmission of this negative off-response. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate the efficacy of a simple intravitreal injection of perfluoropropane (C3F8) in treating unclosed idiopathic macular holes (IMHs) in patients who had previously undergone primary pars plana vitrectomy (PPV). Methods: This study was a retrospective, observational clinical study. It included patients diagnosed with unclosed IMHs following primary PPV combined with internal limiting membrane peeling and air tamponade. Optical coherence tomography (OCT) performed 1 week after PPV revealed unclosed IMHs with the presence of the 'cuff' sign and intraretinal cysts. The following day, these patients received a simple intravitreal C3F8 injection. Comprehensive evaluations, including best-corrected visual acuity (BCVA), indirect ophthalmoscopy, fundus photography, and OCT, were performed before PPV, 1 week after surgery, and at follow-up intervals of 1–3 months after the intravitreal gas injection. Results: The minimum linear diameter (MLD) of the macular holes (MHs) 1 week before C3F8 injection was 335.1 ± 74.3 μm. Following C3F8 tamponade, the closure rate of the MHs was 100%. The mean BCVA before C3F8 tamponade was 0.68 ± 0.17 logMAR (20/100) after primary PPV, which improved to 0.48 ± 0.19 logMAR (20/63) after C3F8 tamponade, showing a statistically significant difference (P = 0.01). Conclusions: For patients with unclosed MHs after primary PPV, the presence of the 'cuff' sign on OCT suggests that retreatment can be effectively achieved through a simple intravitreal gas injection. This approach is straightforward, practical, and effective. [ABSTRACT FROM AUTHOR]

• Hollow microneedles (HMNs) enable precise, localized intrascleral drug delivery. • Optimal penetration achieved with 30° bevel angle requiring < 2N force. • 3D-printed adapters enhance injection accuracy and reproducibility. • Ex vivo studies confirm effective drug distribution within the scleral layers. • HMNs present a promising alternative to conventional ocular drug delivery methods. Effective drug delivery to the posterior segment of the eye remains a challenge owing to the limitations of conventional methods such as intravitreal injections, which are associated with significant side effects. This study explored the use of hollow microneedles (HMNs) for localized intrascleral drug delivery as a minimally invasive alternative. Stainless steel HMNs with bevel angles of 30°, 45°, 60°, and 75° were fabricated using wire electron discharge machining. The penetration force of these HMNs in ex vivo porcine sclera was assessed using a texture analyser, revealing that the 60° bevel angle required the lowest force (<2N), making it optimal for scleral penetration. To ensure precision in drug delivery, 3D-printed adapters were developed to control the injection angles and volumes. The distribution of a model dye, rhodamine B, was studied via digital imaging, multiphoton microscopy, and confocal microscopy. The results showed that HMNs with a 60° bevel angle could penetrate the sclera to a depth of approximately 450 µm at a 45° injection angle, providing enhanced distribution within the scleral layers. This study confirmed that the use of HMNs enables effective and controlled intrascleral drug delivery, resulting in the formation of localized depots with minimal tissue damage. This research demonstrates the potential of HMNs as a promising alternative to traditional ocular drug delivery methods, offering improved bioavailability and the potential to reduce patient discomfort. [ABSTRACT FROM AUTHOR]

Introduction: Intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents are a primary management option for retinal diseases. Acute elevation of intraocular pressure (IOP) is a complication associated with these injections that should be considered. This study investigated and compared the prophylactic effects of fixed combination anti-glaucoma medication on IOP spikes following intravitreal anti-VEGF injections. Methods: This randomized double-blind clinical trial included one eye of each participant indicated for treatment with intravitreal injection of anti-VEGF agents (bevacizumab, aflibercept, and ranibizumab) and randomly allocated to one of the three prophylactic anti-glaucoma medications, with each drug further divided into one- and two-drop regimens before intravitreal injection. Participants with allergies or contraindications to medications were excluded from the pretreatment groups and were invited to participate in the control group. Results: The study involved 308 participants: 89 in the dorzolamide/timolol group, 86 in the brimonidine/timolol group, 101 in the brinzolamide/brimonidine group, and 32 in the control group. Baseline characteristics and IOP were comparable across all groups. In the prophylactic premedication groups, mean IOP at 30 min were within 21 mmHg and returned to their baseline at 1 h. Mean IOP measurements between baseline and 30 min in the brimonidine/timolol two-drop regimen were not significantly different: 13.72 ± 4.63 vs 15.11 ± 4.39 mmHg, p = 0.096. In the control group, IOP significantly increased from baseline at 30 min and 1 h post-injection: 14.31 ± 4.10, 22.15 ± 8.64, and 18.36 ± 7.52 mmHg, respectively, p < 0.001. Conclusion: Topical fixed combination anti-glaucoma medication used as a prophylactic treatment before intravitreal anti-VEGF injections significantly prevented IOP spikes post-injection, with a comparable effect among three medications. Prophylactic treatment of IOP spikes should be considered as standard care to prevent further damage in patients with compromised retinal vascular and optic nerve perfusion. Trial Registration: TCTR20241005001, retrospectively registered. Plain Language Summary: Drug injection into the eye is a standard treatment for various eye diseases. However, an increase in eye pressure is often observed post-injection. This study focuses on the effect of prophylactic topical antiglaucoma eye drops on pressure of the eye elevation post-injection of drug into the eye. All medications in the study significantly prevented pressure of the eye spikes compared with no treatment. Prophylactic treatment of pressure of the eye spikes should be considered as standard care to prevent further damage to the eye. [ABSTRACT FROM AUTHOR]

Purpose: To compare the anatomical and visual outcomes in eyes with submacular hemorrhage (SMH) treated with a combination of ranibizumab (RBZ) either innovator or biosimilar (Razumab) and intravitreal perfluoropropane gas (C3F8). Methods: Treatment naïve neovascular age related macular degeneration (n-AMD) patients with SMH were retrospectively analyzed. Patients received either innovator or biosimilar RBZ (3 loading doses followed by pro re nata regimen) and single injection of intravitreal C3F8. Optical coherence tomography (OCT) was performed at baseline, 1, 3 and 6 months. Changes in best corrected visual acuity (BCVA) and central macular thickness (CMT) were assessed at 6 months. P value ≤ 0.05 was considered statistically significant. Results: A total of 67 eyes (35 and 32 eyes in innovator and biosimilar group respectively) were analyzed. BCVA improved from 1.15 ± 0.19 to 0.51 ± 0.23 logarithm of minimum angle of resolution (logMAR) in innovator RBZ group (p < 0.001) and from 1.17 ± 0.15 to 0.53 ± 0.20 logMAR in biosimilar RBZ group (p < 0.001). Similarly, mean CMT showed significant reduction in both groups at 6 months (innovator RBZ: 609.5 ± 50.1 μm to 254.3 ± 20.3 μm, p < 0.001; biosimilar RBZ: 602.3 ± 58.9 μm to 251.8 ± 22.3 μm, p < 0.001). Intergroup comparisons between innovator and biosimilar RBZ showed no differences in either BCVA or CMT at all time points (all p values > 0.05). Mean number of intravitreal injections was marginally higher in innovator group compared to biosimilar RBZ (4.37 ± 0.49 vs. 4.22 ± 0.42; p = 0.18). Conclusion: Biosimilar RBZ may act as a viable alternative to innovator RBZ to treat SMH with comparable anatomical and visual outcomes at 6 months. [ABSTRACT FROM AUTHOR]

Background: To report a case of intraocular inflammation (IOI) after intravitreal injection of aflibercept 8 mg for treatment-refractory neovascular age-related macular degeneration. Case presentation: An 80-year-old man with diabetes mellitus had neovascular age-related macular degeneration refractory to treatment with aflibercept 2 mg. Despite ten injections of faricimab, the exudation remained, and we switched to brolucizumab, which resulted in a mild IOI. The IOI improved with only topical steroids, and we switched back to aflibercept 2 mg for the exudation. However, the exudation remained, and we decided to switch to aflibercept 8 mg after careful discussion with the patient. Two weeks later, he experienced minor ocular pain and photophobia. One month later, although a dry macula was achieved, severe visual impairment occurred due to anterior chamber inflammation, retinal vasculitis, and retinal vascular occlusion. We diagnosed the severe IOI following aflibercept 8 mg and immediately started steroid eye drops and a sub-Tenon injection of triamcinolone acetonide. Although the inflammation resolved, his visual acuity did not improve. Conclusions: This case demonstrated a potential dose-dependent inflammatory response following aflibercept 8 mg, which did not occur with aflibercept 2 mg in patients with a history of intraocular inflammation. [ABSTRACT FROM AUTHOR]

Background: Ozurdex® (Allergan®, AbbVie Company, North Chicago, Illinois, EUA), is composed of 0.7 mg of dexamethasone, fused in a solid biodegradable PLGA polymer, whose degradation occurs naturally in the vitreous cavity, usually in six months after its application. Methods: In this study, we included patients aged ≥ 18 years with one or two eyes who had an indication for Ozurdex® implants. Eyes submitted to Ozurdex® application were evaluated in the first hour after the injection via transpalpebral contact B-scan ocular ultrasonography (Aviso® or Compact Touch®, Quantel®) and non-mydriatic ultra-widefield fundus photography (California®, Optos®) performed sequentially. The exams were executed using similar parameters and techniques, by the same ophthalmologist, after every 45 days, until the end of 180 days. The programed visits were the initial (tagged D0) and sequential (D45, D90, D135, and D180) visits, with a possible variance of seven days, before or after. The ultrasonographic Ozurdex® findings evaluated were: non-quantitative: structure, height, reflectivity, artifact production, location, and movement; and quantitative: length and thickness. Ultra-widefield fundus photography parameters were: Ozurdex® visualization, location, and structure. Results: The B-scan showed the implant initially, at the D0 visit, as a well-delimited and homogeneously highly reflective linear and continuous structure. On D45, Ozurdex® implants presented with low internal reflectivity and irregularity in the limits. On D90, D135, and D180, reductions in the length and thickness progressively lessened, leading to the final appearance of a small highly reflective clust. Over time, all the implants presented reductions in length and thickness. The mean length at D0 was 7.42 ± 0.39 mm and at the final visit (D180) it was 1.50 ± 0.47 mm. The mean thickness at D0 was 0.77 ± 0.13 mm and at the final visit (D180) it was 0.44 ± 0.18 mm. Conclusions: Considering implant dimensions, the change in length over time was more evident than the change in thickness. In all the cases where visualization was possible, positive correlations with B-scan findings were found despite changes in patient position. These alterations evidenced in the Ozurdex® implant over time may be related to the degradation of the glucose polymer structure. [ABSTRACT FROM AUTHOR]

Background: The PreserFlo™ MicroShunt (PFMS) is a bleb-forming device considered to be less invasive than traditional glaucoma surgery such as trabeculectomy. This study evaluates the 1-year success rates as well as safety profile of PFMS in patients having high intraocular pressure (IOP) and/or glaucoma refractory to drop therapy with a history of prior intravitreal dexamethasone therapy. Methods: A total of 16 eyes after PFMS implantation due to elevated IOP after intravitreal dexamethasone implant (DEX-I) administration were included in this retrospective cohort study. Success rates and secondary outcomes were evaluated. Results: Qualified and complete success rates at 12 months, respectively, were 14/16 and 12/16 eyes for criterion A, 13/16 and 11/16 eyes for B, 13/16 and 11/16 eyes for C, and 6/16 and 6/16 eyes for D. The overall mean (range) preoperative IOP decreased from 27 (16–38) mmHg to 13 (10–17) mmHg at 12 months. BCVA was not significantly different up to 12 months (p = 0.63). The preoperative mean (range) number of medications decreased from 3.56 (2–4) to 0.31 (0–3) at 12 months. One eye underwent needling twice, and two eyes were revised surgically. One patient needed replacement of the PFMS. There were no hypotony-related complications. Conclusions: The PFMS is an effective surgical option for patients with steroid-induced IOP elevation. It demonstrates satisfactory short-term success rates, a reduced need for pressure-lowering eye drops, an excellent safety profile with minimal postoperative care, and a low complication rate. Additional interventions such as needling or revisions were infrequently necessary. However, PFMS may not be the ideal choice for cases requiring a low target pressure (≤12 mmHg). [ABSTRACT FROM AUTHOR]

Background: Age-related macular degeneration (AMD) is a progressive, chronic eye disease with no permanent cure currently available. Symptoms of the disease, including distorted and blurred vision and gradual loss of central vision, significantly aggravate patients' daily functioning. The purpose of this study was to assess the acceptance of the disease among patients diagnosed with neovascular age-related macular degeneration before treatment and after receiving seven intravitreal injections and to determine how it was related to the values of visual parameters. Methods: This survey-based study was carried out using the author's questionnaire and a standardized research tool, the Acceptance of Illness Scale (AIS). It also involved the analysis of the patients' medical records. Results: The study included 121 patients (121 eyes), including 60 women and 61 men. The age range of the participants was 51–90 years. The mean and median age of the participants was 75 years. After undergoing a series of intravitreal injections, statistically significant improvements were observed in the degree of illness acceptance according to the AIS score. Data analysis revealed that the degree of disease acceptance was significantly related to visual acuity and contrast sensitivity. Conclusions: The acceptance of the disease among the study participants from the beginning of the therapy until receiving a series of seven intravitreal injections was at an average level. Acceptance of the disease was better before the beginning of the therapy, due to higher values of corrected visual acuity, and after the therapy, because of higher values of contrast sensitivity and corrected visual acuity. [ABSTRACT FROM AUTHOR]

Aflibercept and brolucizumab, two anti-VEGF agents used as intravitreal injections in ophthalmology, differ significantly in molecular weight (aflibercept—115 kDa and brolucizumab—26 kDa). Using aqueous humor samples collected after drug administration, we measured and performed a comparative analysis of pharmacokinetics and half-lives of these drugs in the human eye. Since the quantification of monoclonal antibodies (mAbs) using antigen–antibody reactions, such as ELISA, is influenced by endogenous ligands or anti-drug antibodies, we employed nano-surface and molecular-orientation limited proteolysis (nSMOL), combined with liquid chromatography–tandem mass spectrometry (LC-MS/MS), for accurate measurements. Aqueous humor samples were collected from 59 eyes of 59 patients treated with aflibercept and 52 eyes of 52 patients treated with brolucizumab. Samples were obtained with a median post-injection period of 30 (range, 2–49) days for aflibercept and 28 (range, 4–60) days for brolucizumab. A population pharmacokinetic (PPK) analysis revealed that the half-life of aflibercept in human aqueous humor was significantly shorter than that of brolucizumab, 2.88 days versus 9.00 days, respectively (p = 1.16 × 10−7). Using the same mass spectrometry conditions, we calculated the half-lives of the two drugs. These results may be useful for optimizing the efficacy of these drugs in clinical practice. [ABSTRACT FROM AUTHOR]

AbstractPurposeMaterials and methodsResultsConclusionsIntravitreal bevacizumab has been utilized to mitigate radiation retinopathy, yet the potential role of intravitreal melatonin for its prevention remains unexplored. This study aims to evaluate and compare the efficacy of intravitreal melatonin and bevacizumab in preventing radiation retinopathy in an experimental animal model.Twelve healthy male New Zealand white rabbits (n = 24 eyes) received a single 3000 cGy irradiation dose in both eyes. Intravitreal melatonin (100 mcg/kg = 300 mcg/0.05 mL) was administered to the left eyes of six rabbits, and bevacizumab (1.25 mg/0.05 mL) to the left eyes of the remaining six, with sham injections given to the right eyes as controls. Six weeks after irradiation, bilateral enucleation was performed for biochemical and histopathological evaluation.Oxidative stress markers did not differ significantly between the groups (p = .827). Both melatonin and bevacizumab treatments markedly reduced axonal damage compared to the sham control group (p < .001). Melatonin also demonstrated a trend toward superior neuroprotective effects relative to bevacizumab, though this difference was not statistically significant (p = .07).Intravitreal melatonin demonstrated efficacy comparable to bevacizumab in reducing radiation-induced retinopathy, with an encouraging trend toward enhanced neuroprotection. These findings position melatonin as a potential novel therapeutic for radiation retinopathy prophylaxis. Further research with larger, long-term studies is warranted to validate these results and investigate melatonin’s broader applications in retinal protection. [ABSTRACT FROM AUTHOR]

Objective: To perform a systematic literature review analyzing visual outcomes of immediate, early, and delayed vitrectomy in the treatment of acute endophthalmitis after intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections. Methods: We conducted a literature search using the Ovid Medline, Embase.com, and Web of Science databases, and relevant articles were selected from original English papers published from 2005 to 2021. Inclusion criteria were studies reporting cases of acute post-anti-VEGF endophthalmitis, defined as occurring within 6 weeks of injection treatment. Exclusion criteria were pediatric cases and cases explicitly reported to be caused by injections of contaminated drugs. Risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal tool for case reports and case series. The study dataset for descriptive and statistical analysis comprised patient-level data extracted from included studies. The timing of vitrectomy compared were defined as (1) immediate vitrectomy as occurring within 24 h of endophthalmitis diagnosis; (2) early vitrectomy as occurring between 24 and 48 h of endophthalmitis diagnosis; (3) late vitrectomy as occurring after 48 h of endophthalmitis diagnosis. Primary outcome was final visual acuity following treatment with vitrectomy. Results: Twenty-five articles were published that met our inclusion and exclusion criteria for a total of 86 cases. Thirty-seven were immediate vitrectomy, 25 were early, and 24 were late vitrectomy treatment groups, respectively. We observed differences in final visual outcomes and in improvement from diagnosis to final visual acuity, with patients receiving immediate and late vitrectomy to have better final visual outcomes than those patients receiving early vitrectomy (p < 0.005). Conclusion: Our results show that there may be an association between time to vitrectomy and visual outcomes. Immediate and late vitrectomy treatment groups had better visual outcomes than the early group. Our results were limited by the reliance on case reports and series and the paucity of data available specifying the timing of vitrectomy. Additional research is necessary to elucidate the effects of treatment timing in patients with endophthalmitis following anti-VEGF injection. Plain language summary: Timing of vitrectomy for treatment of endophthalmitis after intravitreal anti-VEGF injection: a systematic literature review of case reports and series In this study, we aimed to review existing literature to assess the associations between timing of surgery to treat endophthalmitis following intravitreal anti-VEGF injection and visual outcomes. The timing of vitrectomy compared were defined as (1) immediate vitrectomy as occurring within 24 hours of endophthalmitis diagnosis; (2) early vitrectomy as occurring between 24-48 hours of diagnosis; (3) late vitrectomy as occurring after 48 hours of diagnosis. We found 25 articles with 86 total cases. We observed differences in final visual outcomes and in improvement from diagnosis to final vision, with patients receiving immediate and late vitrectomy to have better final vision than those patients receiving early vitrectomy. [ABSTRACT FROM AUTHOR]

Autophagic dysfunction-induced deterioration of the retinal microenvironment drives the progression of wet age-related macular degeneration (wAMD). The efficacy of single-target anti-VEGF antibodies in treating wAMD has long been suboptimal due to the intricate interplay between autophagy dysfunction, oxidative stress, and angiogenesis. Here, we introduce an intravitreal hydrogel depot, named Rab&Rapa-M@G, consisting of rapamycin-loaded microemulsion (Rapa-M, an mTOR inhibitor), ranibizumab (anti-VEGF antibody), and a thermosensitive hydrogel matrix. A single intravitreal injection of Rab&Rapa-M@G can sustainably deliver Rapa-M and ranibizumab to the retinal pigment epithelium for at least 14 days. This formulation significantly improves retinal autophagic flux homeostasis and reduces oxidative stress injury in wAMD mice by modulating the AMPK/mTOR/HIF-1α/VEGF and AMPK/ROS/HO-1/VEGF pathways. Consequently, it synergistically disrupts the "autophagic dysfunction-oxidative stress-angiogenesis" loop, leading to a remarkable reduction in choroidal neovascularization area and retinal damage compared to ranibizumab alone. Notably, the sequential administration of ranibizumab and Rab&Rapa-M@G further enhances the overall anti-wAMD efficacy, achieved through sequential delivery of Rab and Rapa, allowing for a more precise grasp of the treatment window. In conclusion, this hydrogel depot design, with its sequential and sustained delivery of mTOR inhibitors and anti-VEGF antibodies, offers a promising strategy for multi-target synergistic therapy in wAMD. [Display omitted] • Microemulsion-doped hydrogel enables sustainable co-delivery of Rab and Rapa to retina. • The drug combination disrupts the "autophagy-oxidative stress-angiogenesis" loop. • Sequential release of therapeutics accurately targets the treatment window. [ABSTRACT FROM AUTHOR]

Background: This study evaluates the efficacy of intravitreal Faricimab in reducing pigment epithelium detachment (PED) and fluid volumes in both treatment-naïve eyes and eyes unresponsive to anti-VEGF mono-therapies, all diagnosed with type 1 macular neovascularization (T1 MNV) over a period of 12-month. Methods: A retrospective, single-center cohort study was conducted at the Jules Gonin Eye Hospital, Lausanne, Switzerland. Clinical records of treatment-naïve and non-responder switch patients presenting T1 MNV secondary to neovascular age-related macular degeneration (nAMD) from September 2022 to March 2023 were reviewed. Patients received a loading dose of three monthly Faricimab injections followed by a treat-and-extend (T&E) regimen. Multimodal imaging, including structural OCT and AI-assisted analysis, was used to quantify PED volumes and related fluid biomarkers at baseline, 3-month, 6-month, and 12-month follow-up. Statistical analyses included linear mixed models to evaluate differences and trends in intraretinal (IRF), subretinal fluid (SRF) and PED volumes. Results: 65 eyes of 65 patients were enrolled (female: 70.7%; mean age = 80.7yrs, SD = 6.9yrs). 80% had received anti-VEGF treatment (Switch group) and 20% were treatment-Naïve at baseline. At 12 months, intravitreal treatments were more frequent in the Switch group (mean number = 8.3 vs. 6.0; p = 0.009). BCVA improved at the 12-month follow-up in Naïve eyes (+ 6.9 ETDRS letters from baseline, p = 0.053) and was maintained in Switch eyes. No cases of intraocular inflammation were observed. Significant reduction in SRF and IRF volumes were noted in both groups. A significant reduction in PED volume was observed over the follow-up period in both groups (mean slope = -206 nL, 95%CL = -273/-138; p-value < 0.001). Conclusions: Intravitreal Faricimab significantly reduced PED volumes in both treatment-Naïve and non-responder Switch patients over 12 months. The study highlights Faricimab's potential as an effective treatment option for T1 MNV in nAMD, offering significant improvements in PED volume and related fluid biomarkers. [ABSTRACT FROM AUTHOR]

Background: To analyse the effect of suprachoroidal injection (SChI) of triamcinolone acetonide (TA) on macular thickness (CRT), ectopic inner foveal layer thickness (EIFL-T) and best corrected visual acuity (BCVA) in pseudophakic patients undergoing vitrectomy for epiretinal membrane (iERM) compared to intravitreal injection of TA (IVTA). Methods: Prospective matched comparison of patients undergoing vitrectomy for Govetto stage 3 and 4 iERM. 25 eyes receiving IVTA (G-1) were compared to 23 eyes receiving SChI-TA (G-2) during vitrectomy. Primary outcome was change in BCVA, CRT, EIFL-T before surgery and 1, 3 and 6 months after surgery. Secondary outcome was the incidence of cystoid macular edema (CME). Results: Six months after surgery, G2 had a greater mean reduction in CRT (−222 µm vs −131 µm) and EIFL-T (−200 µm vs −104 µm) than G1. BCVA improved more in G2 than in G1 (p = 0.02). Foveal depression reformed in 43% of cases in G-2 and 16% of cases in G-1. Incidence of postoperative CME was 16% in G-1 and 4.3% in G-2. Conclusions: During vitrectomy for iERM, SChI-TA was more effective than IVTA in reducing CRT and EIFL-T and improving BCVA. SChI-TA was effective in preventing postoperative CME. SChI-TA treatment was safe and reproducible and did not affect postoperative IOP. Trial registration NP6289—June 18th, 2024 (retrospectively registered). [ABSTRACT FROM AUTHOR]

Purpose: We report three cases of occlusive vasculitis following intravitreal rituximab therapy for biopsy-proven primary vitreoretinal lymphoma (PVRL), one of which was following an injection of the biosimilar Riabni (rituximab-arrx, AmGen) and two of which were following an injection of Rituxan (rituximab, Genentech). Methods: Case series. Results: Three cases of occlusive vasculitis confirmed with fluorescein angiography are reported 5 days, 8 days, and 3.5 weeks following intravitreal injection of rituximab. The initial vision was poor (20/500, 20/150, and light perception), but vision recovered to baseline in two cases, and remained poor in the case of combined artery and vein occlusion. Conclusion: Occlusive vasculitis is a rarely reported but potential complication of intravitreal rituximab therapy in patients who have been previously treated with the agent and may have delayed onset. A low threshold for fluorescein angiography as a diagnostic test for post-injection vision loss and prompt treatment with topical and/or oral steroids should be considered. [ABSTRACT FROM AUTHOR]

Purpose: To present a case of aspergillus-induced endogenous endophthalmitis evolving into delayed lumbosacral osteomyelitis, initially misdiagnosed as ankylosing spondylitis (AS) in an immunocompetent patient. Method: Case Report. Results: A 38-year-old woman, initially treated for pneumonia, experienced sudden loss of vision in her left eye, prompting a thorough examination that revealed a distinct chorioretinal infiltrate. Microbiological analysis of the patient's vitreous samples detected Aspergillus fumigatus, leading to the diagnosis of endogenous endophthalmitis. Treatment involved vitrectomy, intravitreal injections, and intravenous amphotericin B. Two months later, she was referred for lower back pain, misdiagnosed as AS. Lumbosacral biopsy confirmed Aspergillus involvement once more, necessitating antifungal therapy. Conclusion: This case highlights the atypical progression of Aspergillus-induced endogenous endophthalmitis to delayed lumbosacral osteomyelitis in an immunocompetent individual. It highlights the crucial role of a meticulous medical history examination and interdisciplinary collaboration in diagnosing and managing diseases, especially in cases with atypical presentations. [ABSTRACT FROM AUTHOR]

Retinal neovascularization (RNV) is a key pathological process in many blinding disorders. This study aims to investigate the potential mechanisms of heme oxygenase-1 (HO-1) on ferroptosis during RNV. Through bioinformatics analysis, differentially expressed ferroptosis-related genes were identified in the oxygen-induced retinopathy (OIR) mouse model. Ferroptosis was assessed in the OIR model and the human retinal microvascular endothelial cells (HRECs) with the treatment of H 2 O 2. The mRNA and protein levels were measured through RT-qPCR and western blot. Lipid peroxidation was assessed through C11-BODIPY staining. HO-1 expression was knocked down by intravitreal injection with a self-complementary adeno-associated virus in the OIR model and small interfering RNA in HRECs. The pathological neovascular area and avascular area were assessed through immunofluorescent staining. The cellular functions of HRECs were evaluated with migration and tube formation assays. Our results demonstrated that HO-1 was significantly upregulated in the OIR model. 4-HNE upregulation and GPX4 downregulation were observed in the OIR model. The H 2 O 2 -induced oxidative stress resulted in lipid peroxidation, GPX4 downregulation, and mitochondrial morphology changes in HRECs. HO-1 knockdown induced GPX4 upregulation, and decreased lipid peroxidation in vitro and in vivo. Furthermore, HO-1 inhibition reduced pathological RNV in the OIR model and attenuated migration and tube formation in HRECs. Treatment with 6-OHDA restored the decrease of VEGFA, migration, and tube formation caused by HO-1 knockdown in HRECs. Overall, HO-1-mediated ferroptosis can regulate RNV through the COX2/VEGFA signal axis. These findings suggest that targeting HO-1 may serve as a promising approach for treating retinal neovascular diseases. [Display omitted] • HO-1 was a significantly upregulated ferroptosis-related gene in the OIR model. • Knockdown of HO-1 suppresses ferroptosis in both the OIR model and HRECs. • HO-1 knockdown reduces retinal neovascularization and inhibits functions of HRECs. • HO-1-mediated ferroptosis regulates pathological RNV via the COX2/VEGFA axis. [ABSTRACT FROM AUTHOR]

We evaluate the pharmacokinetics, safety, and optimal dosages of intravitreal agents in silicone oil (SO)-filled eyes, addressing challenges in administering such therapies. We assessed the pharmacological properties and safety profiles of intravitreal drugs in SO-filled eyes, deriving conclusions and guidance from available literature and expert consensus. Preclinical data suggest comparable half-lives of anti-vascular endothelial growth factoragents in SO-filled eyes, but clinical evidence is mainly from case reports and small series. Available research prioritizes standard dosages, particularly for bevacizumab (1.25 mg), supported by stronger evidence than aflibercept (2 mg) or ranibizumab (0.5 mg). Intravitreal steroids, especially dexamethasone at 0.7 mg, show efficacy and safety, while evidence for fluocinolone acetonide at 0.19 mg is limited. Intravitreal methotrexate has been reported at the dosage of 250–400 μg, with keratitis as the primary expected side effect. Case reports indicate tolerability of standard dosages of antivirals (foscarnet 1.2–2.4 mg/0.1 mL, ganciclovir 4 mg/0.1 mL) and the antibiotic combination piperacillin/tazobactam (250 μg/0.1 mL). We offer guidance based on current, but limited, literature. Standard dosage of intravitreal agents should be carefully considered, along with close monitoring for potential side effects, which should be discussed with patients. [ABSTRACT FROM AUTHOR]

Purpose: To characterize private equity (PE) acquisition of ophthalmology and optometry practices and compare procedural utilization before and after acquisition. Methods: Ophthalmologists and optometrists in practices acquired from 2012 to 2016 were identified and characterized using an internet archive with an additional search in 2017 to characterize doctor turnover. United States Census Bureau and Internal Revenue Service Data were used to determine population health insurance and adjusted gross income (AGI). Healthcare Common Procedure Coding System codes were drawn from the Medicare database. Results: Six platform companies acquired 36 practices between 2012 and 2016, including 518 optometrists and 136 ophthalmologists with a net doctor decrease of 3% and 7%, respectively (years 2016 to 2017). PE firm-owned practices were primarily located in metropolitan core areas with above-average AGI and insurance coverage. Diagnostic procedures, total encounters, cataract surgery, and yttrium aluminum garnet (YAG) capsulotomy volume increased per physician 1-year post-acquisition. In adjusted difference-in-difference comparisons, cataract surgery (13.3% relative increase, P <0.001) and YAG capsulotomy (35.6% relative increase, P <0.001) remained significant. PE practices demonstrated an increase in cataract surgery procedures (28,813/platform pre-acquisition to 33,930/platform post-acquisition, P =0.015). Conclusion: PE acquisitions of ophthalmology and optometry practices were centered in metropolitan core areas with above-average AGI and insurance coverage. PE acquisition led to less optometrists and ophthalmologists employed at the practice. Overall, they exhibited doctor turnover with a net doctor decrease. When compared to non-PE doctors, PE-acquired doctors demonstrated an increase in cataract surgery and YAG capsulotomy volume. Overall, cataract surgery volume increased among PE practices after acquisition. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to compare the efficacy of the treat-and-extend (TAE) regimen versus the pro re nata (PRN) regimen in patients with bevacizumab-resistant diabetic macular edema (DME) treated with aflibercept, with or without adjunctive laser therapy. Methods: Ninety-one eyes from 91 patients who were switched to aflibercept after three consecutive intravitreal bevacizumab injections for the treatment of DME were included in this retrospective real-world study. The patients were categorized into three groups: TAE (n = 30), TAE + laser (n = 31), and PRN (n = 30). Changes in best-corrected visual acuity and central macular subfield thickness (CMST) at 12, 24, and 52 weeks were defined as the primary functional and anatomical outcomes. Results: A total of 91 eyes from 91 patients (49.5% female) with a mean age of 63.9 ± 7.1 years were included in the analysis. At 52 weeks, the mean letter gains were 8.03, 8.90, and 10.23 in the TAE, TAE + laser, and PRN groups, respectively. Anatomical improvements, as measured by CMST reduction, were 55.33 µm, 33.35 µm, and 48.96 µm in the TAE, TAE + laser, and PRN groups, respectively. The average number of injections administered was 7.7, 8.1, and 8.1, respectively. The final extension interval for the TAE group was 8.7 weeks, compared to 9.5 weeks in the TAE + laser group. Conclusions: The PRN group demonstrated the highest functional improvement while the TAE group showed the greatest anatomical improvement. Overall, both anatomical and functional outcomes in the TAE regimen were comparable to the PRN regimen in patients with bevacizumab-resistant diabetic macular edema. [ABSTRACT FROM AUTHOR]

Introduction: This study aims to evaluate the ocular and systemic safety profiles of intravitreal biosimilar ranibizumab Ranieyes (Lupin Pharmaceuticals, Mumbai, India) in real-world clinical settings across multiple chorioretinal vascular diseases, including neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), and retinal vein occlusion (RVO) in adults. Methods: We conducted a retrospective, consecutive, interventional, uncontrolled multicenter study using data from three hospital networks in India. A total of 1401 eyes received 2194 injections of Ranieyes between June 2022 and November 2023. Patients were followed for a minimum of 6 months, and data on ocular and systemic adverse events (AEs) were collected and analyzed. Results: The study population included 636 male patients and 533 female patients, with a mean age of 58.63 ± 11.54 years. The average number of injections per eye was 1.49 ± 0.23, with the highest frequency in the nAMD group (mean of 2.3 ± 0.23 injections per eye) over 6 months. Non-serious adverse events (nsAEs) were observed in 26.83% of injections, with mild ocular pain and transient blurring of vision being the most common. Serious ocular adverse events were rare, occurring in 0.85% of eyes, with retinal pigment epithelial tear (RPE TEAR) being the most frequent. Systemic adverse events were noted in 5.03% of patients, and all but one were non-serious. One patient developed non-fatal myocardial infarction, the causal relationship of which, however, was not established with the intravitreal agent used. No cases of endophthalmitis were observed. Conclusions: This large-scale, real-world study demonstrates that Ranieyes is a safe intravitreal antivascular endothelial growth factor (anti-VEGF) agent across various chorioretinal vascular diseases. The safety profile of Ranieyes is consistent with that of the reference product, making it a viable option in resource-constrained settings. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the outcome and ocular adverse events of bedside bilateral sequential intravitreal anti-vascular endothelial growth factor injections for retinopathy of prematurity (ROP) (BBSIR). Methods: This retrospective interventional study included infants who received BBSIR with a follow-up of at least 1 month. Clinical history, intravitreal injection details, indications, intraoperative and postoperative ocular adverse events, and outcomes were analyzed. Results: The study cohort included 192 babies (384 eyes) spread over 9 years. The mean gestational age was 30.2 ± 2.6 weeks (28.8–34.1), and the birth weight was 1098.11 ± 271.65 g (650–2000). The indications for BBSIR were as follows: 73.4% (n = 141 infants) were too sick to transfer to an ophthalmic unit, 10.9% (n = 21 infants) due to the parents' inconvenience of traveling to the ophthalmic center, and 15. 6% (n = 30 infants) due to both reasons. The injections were given by an ROP specialist/ROP-trained ophthalmologist after due parental consent, considering each eye as a fresh eye with separate scrubbing and draping. Light from the head-worn indirect ophthalmoscope served as the source of illumination. The retinopathy was regressing/regressed in 92.4% of babies until the last follow-up. The major ocular complication was cataract in 2 eyes (0.5%). There was no incidence of endophthalmitis till last follow-up (median 5.7 months). Conclusions: As per this study, BBSIR was observed to be effective and safe if given by those fully trained in the management of ROP. Though the rate of complications like cataract is small, they can pose management challenges and impact vision in a growing child. [ABSTRACT FROM AUTHOR]

The management of intermediate and posterior uveitis poses a significant challenge of achieving adequate drug concentrations in the posterior segment over the chronic nature of the disease. Systemic agents seldom reach effective drug levels, and even with low maintenance or tapering doses, it is hard to avoid systemic toxicity. The use of intravitreal and periocular injections is often unable to prevent recurrences due to their short half-life. Since the emergence of intravitreal implants (Vitrasert, Retisert), it has become possible to circumvent these therapeutic challenges. A detailed review in the PubMed index yielded 155 articles, of which 22 were analyzed based on exclusion criteria. A recent shift from surgically sutured to minimally invasive injectable implants mainly indicated for noninfectious uveitis is evident from the literature. This review article also provides insights into dexamethasone (Ozurdex) and recent fluocinolone acetonide (Yutiq, Iluvien) implants with particular emphasis on their improved safety and efficacy. Dexamethasone implants favor the therapeutic goal of prevention of recurrences, whereas the use of fluocinolone implants helps to attain better visual outcomes due to their longer duration of action. Thus, the review provides recent literature supporting the role and indication of sustained release intravitreal implants in the management of noninfectious intermediate and posterior uveitis. [ABSTRACT FROM AUTHOR]

Background/Objectives: This study aimed to evaluate the clinical characteristics and identify the prognostic factors affecting visual outcomes, retinal detachment, and recurrence in cytomegalovirus retinitis (CMVR) patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: A retrospective analysis of 54 CMVR patients (84 eyes) who underwent allo-HSCT between 2015 and 2024 was conducted. Ophthalmologic and systemic evaluations were performed. The visual outcomes were classified as improvement, stabilization, and deterioration. Logistic regression and LASSO regression models were used to identify the prognostic factors. Results: Improved or stabilized visual outcomes were found in 22 eyes, while 62 eyes suffered from deterioration. Larger lesion areas were independently associated with poorer visual outcomes (OR 0.989, p = 0.002). Eight (9.5%) eyes had rhegmatogenous retinal detachment and thirteen (15.5%) eyes suffered from recurrence. Retinal detachment was significantly predicted by higher baseline aqueous CMV DNA load (OR 5.087, p = 0.026). Macula involvement (OR 5.322, p = 0.032) and more intravitreal injections (IVs) (OR 1.263, p = 0.008) were independent risk factors for recurrence. No systemic factors were found to be associated with the clinical outcome of eyes with CMVR. Conclusions: Ocular characteristics, rather than systemic factors, were more useful to predict the clinical outcome of eyes with CMVR. Routine ophthalmic screening and early intervention are essential to improving outcomes in this vulnerable population. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the etiology, pathogens, antibiotic susceptibility, treatments, and factors influencing the visual prognosis of pediatric post-traumatic endophthalmitis (PTE) to provide valuable insights for clinical diagnosis and treatment. Results: A total of 301 children were included, with 142 (47.2%) cultures yielding positive results. Gram-positive cocci were the predominant pathogens (71.1%), with high sensitivity to vancomycin (95.4%). Pars plana vitrectomy (PPV) was performed in 216 eyes (71.8%), with emergency or immediate vitrectomy within 24 h of hospitalization performed on 171 eyes (56.8%). The first intravitreal antibiotic injection, consisting of ceftazidime and norvancomycin, was administered to 248 patients (82.4%). The absence of retinal detachment (OR, 0.191; 95% CI, 0.065–0.560; p = 0.002), normal intraocular pressure (OR, 1.894; 95% CI, 1.151–3.117; p = 0.012), and no lens extraction (OR, 0.187; 95% CI, 0.069–0.504; p < 0.001) were found to be independent factors associated with better visual outcomes (BCVA) in pediatric PTE patients. Methods: A retrospective analysis was conducted on pediatric PTE patients treated between January 2012 and June 2022. Data were collected on clinical characteristics, causative pathogens, antibiotic sensitivity, treatments, and visual outcomes. Conclusions: Gram-positive cocci are the most common pathogens in pediatric PTE, with early vitrectomy and intravitreal ceftazidime and norvancomycin being the most effective treatments. Favorable visual outcomes are strongly associated with the absence of retinal detachment, normal intraocular pressure, and no lens extraction. These findings highlight the need for timely surgical and antimicrobial interventions tailored to each patient to improve visual prognosis. [ABSTRACT FROM AUTHOR]

Background: Intravitreal anti-vascular endothelial growth factor (VEGF) treatment for diabetic macular oedema (DME) may begin with several initial monthly doses. Characteristics, treatment patterns and outcomes were compared for eyes with DME that did and did not receive such initial doses. Methods: This was a retrospective database study using American Academy of Ophthalmology Intelligent Research in Sight® Registry data (01/01/15–31/12/20; index period). Eligible adults had documented DME within 2 months of first anti-VEGF treatment (index date), data available for 12 months beforehand, and ≥ 1 visual acuity (VA) recording ≤ 60 days before index date. Eyes must have received intravitreal anti-VEGF injections during the index period, but none in the prior 12 months. Characteristics and outcomes for eyes with initial doses (three injections within 100 days of index date) were compared with those without. Multivariate Cox Proportional Hazards modelling estimated predictors for treatment discontinuation, re-initiation, or switch; Generalized Estimating Equations-adjusted modelling estimated characteristics associated with receiving initial doses. Demographics and characteristics were summarised. Injection frequency and number, and VA were determined annually for ≤ 6 years. Discontinuations, reinitiations and switches were compared. Results: Included were 217,696 eyes (n = 77,769 initial; n = 139,927 non-initial) from 166,868 patients. Mean (SD) baseline VA was numerically higher for eyes with versus without initial doses (63.0 [18.1] vs. 62.5 [19.8] letters); this remained during follow-up. Based on modelling results, Eyes with initial doses received more injections (mean [standard deviation (SD)] 11.6 [8.9] vs. 6.1 [6.8] injections) more frequently (interval 7.6 [2.8] vs. 12.6 [7.7] weeks) than eyes without. These differences occurred across follow-up years. Discontinuation (45.7% vs. 63.8%), re-initiation (17.2% vs. 25.0%), and switch (24.5% vs. 31.5%) were less common with initial doses. Asian, Black, and patients of other/unknown race were less likely (P < 0.01) to receive initial doses than White patients, as were Medicare/Medicaid-insured patients versus commercially insured patients (P < 0.01). Conclusions: Various sociodemographic factors associate with initial anti-VEGF doses, including race, ethnicity and insurance. Although eyes with frequent initial doses maintained higher VA than those without, they also receive more injections over time. Further research may elucidate the impact of frequent initial doses versus total injection number on DME outcomes. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate early response of retinal sensitivity (RS) and retinal morphology in diabetic macular edema (DME) patients after intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment. Methods: Sixteen eyes of 12 DME patients were included in this study conducted prospectively. All eyes underwent functional and morphologic examination of the macular area using microperimetry and optical coherence tomography (OCT) before and after intravitreal anti-VEGF injection. To determine significant differences between the values, paired t test was used. A correlation between CMT and RS was made using Spearman's test. Results: Patients were evaluated at baseline, one week and one month after injection. The central macular thickness (CMT) decreased significantly from 449.33 ± 100.79 μm to 427.94 ± 85.76 μm to 357.93 ± 75.92 μm. The RS improved significantly from 7.94 ± 6.43 dB to 11.09 ± 7.42 dB at one week and to 14.22 ± 7.66 dB at one month after treatment. The CMT was significant negatively correlated to RS (r=-0.259, p = < 0.001), with decay of 0.025 dB for every 1 μm increase of CMT. Conclusions: Retinal thickening due to DME can be adequately quantified using OCT, while microperimetry can offer information about retinal sensitivity in the exact location. Therefore, microperimetry can be a useful tool in predicting the functional outcome and determining the efficacy of anti-VEGF treatment for DME patients. [ABSTRACT FROM AUTHOR]

PurposeMethodResultConclusionTo report a case of exudative retinal detachment (ERD) in a child with Acute retinal necrosis (ARN).Retrospective Chart Review.A six-year-old boy presented with anterior uveitis with hypopyon and exudative retinal detachment with peripheral confluent patches of retinitis in the left eye. Examination of the right eye was unremarkable. B scan ultrasonography of the left eye revealed moderate vitreous echoes along with a membrane in the inferior quadrant persisting on low gains indicating localised inferior retinal detachment with the presence of shifting fluid. Fundus examination under general anaesthesia failed to locate any break in the retina. Polymerase chain reaction from the aqueous aspirate was positive for Herpes Simplex Virus (HSV)-I. The child was treated with intravenous acyclovir three times a day, intravitreal injection of ganciclovir and subsequently started on oral steroids (0.5 mg/kg/day). While continuing antiviral treatment, dose of corticosteroid was gradually increased to 1 mg/kg/day. Intravenous injection of acyclovir for 28 days and six intravitreal injections with corticosteroid led to complete resolution of ERD. Six months after initial presentation, the patient underwent lens aspiration with intraocular lens (IOL) implantation under general anaesthesia, under antiviral coverage. Following surgery, his BCVA in the left eye improved to 6/12.ERD is a rare complication of ARN, typically associated with HSV infection. Meticulous monitoring and combined systemic and local antiviral therapy, complemented by judicious corticosteroid use, are essential for managing such cases effectively. [ABSTRACT FROM AUTHOR]

Background: Intravitreal injections, a relatively recent treatment in ophthalmology, is being adopted rapidly worldwide and becoming one of the most common therapies in the field. Numerous complications are associated with this treatment, ranging from minor inflammatory ailments to endophthalmitis. We analyzed the conjunctival flora of patients treated with intravitreal injections and topical antibiotics. Methods: The study was a longitudinal prospective analysis of cultures and antibiograms collected from patients who underwent intravitreal injections and topical antibiotics afterwards at the retina clinic in ABC's Medical University. Results: A total of 148 swabs obtained from 98 patients were cultured and underwent antibiotic sensitivity testing. All bacteria were sensitive to vancomycin, and with the exception of Escherichia coli samples, they were also sensitive to a third-generation cephalosporin (ceftriaxone—same class and generation as ceftazidime), both of which are important antibiotics for the treatment of endophthalmitis. The bacteria species were specifically coagulase-negative Staphylococcus sp. 92% of which was penicillin-resistant and 56.9% was resistant to ciprofloxacin, a second-generation fluoroquinolone. The culture results were similar to that described in the literature and showed the same higher prevalence of coagulase-negative Staphylococcus sp. and S. epidermidis. Regarding the antibiotic resistance profiles, vancomycin, a third-generation cephalosporin, and penicillin showed almost identical results to those reported previously. Regarding fluoroquinolones, the incidence of resistant coagulase-negative Staphylococcus sp. was lower than the findings worldwide, but the resistance rates found were: S. aureus (26.7%), S. epidermidis (61.3%), and Staphylococcus sp. (coagulase negative, 56.9%). Conclusions: The current results showed that the typical conjunctival bacteria had higher resistance to fluoroquinolones (although they were not tested specifically to ofloxacin), suggesting a possible selection of resistant bacteria that should not be taken for granted in clinic. However, the same bacteria did not exhibit cross-resistance in the analysis of vancomycin and third-generation cephalosporins. This real-world, longitudinal, prospective study on conjunctival flora analyzed bacterial resistance profiles and contemporary antibiotic use, offering deeper insights into this subject. [ABSTRACT FROM AUTHOR]

Background/Objectives: Microaneurysms (MAs) are important in the pathology of diabetic macular edema (DME) and its response to anti-vascular endothelial growth factor (VEGF) therapy. This study aimed to clarify the morphological characteristics of MAs in residual edema following consecutive faricimab injections, a bispecific antibody against angiopoietin-2 and VEGF. Methods: We selected patients with DME who exhibited residual edema after three monthly injections of faricimab. In both the residual and absorbed areas of edema, we counted the turnover of MAs, including those that were lost and those that were newly formed. The total number of MAs was determined based on the merged images from an optical coherence tomography (OCT) map and fluorescein angiography. Results: A total of 8 of the 42 patients who received three monthly injections of faricimab showed residual edema one month after the injections. In the residual edema, the density of MAs and the number of maintained MAs were significantly higher (p = 0.04), while the number of disappeared MAs (p = 0.04) and MA turnover (p = 0.01) were lower compared to the absorbed areas. Among the MAs that persisted after the initial injection, the proportion of large-sized MAs (p = 0.01) and their density were significantly greater than those in the absorbed area. In conclusion, the residual areas following three doses of faricimab displayed a higher MA density, less MA loss, and a high density of large-sized MAs compared to the absorbed areas. Our data suggest that large-size MAs located in the residual edema are characteristic of DME cases refractory to faricimab treatment. [ABSTRACT FROM AUTHOR]

Introduction: Vasoproliferative retinal tumors (VPRTs) are rare, benign retinal lesions characterized by abnormal vascular proliferation. They may appear sporadically or with systemic conditions like von Hippel-Lindau disease, often resembling other retinal lesions and posing diagnostic challenges. VPRTs can lead to vision loss if not adequately managed. Current management ranges from observation to different treatment strategies, from laser photocoagulation, photodynamic therapy, cryotherapy to intravitreal injections and vitrectomy. However, optimal approach is still debated due to VPRTs’ rarity and varied presentations. Case Presentations: This series presents three VPRT cases. The first, a 73-year-old man who presented with sudden vision loss due to a VPRT-related vitreous hemorrhage, required multiple interventions, including vitrectomies and anti-VEGF injections, but suffered recurrent macular edema and glaucoma, requiring ongoing management. The second, a 42-year-old asymptomatic man, showed lipid exudation and peripheral retinal detachment, needing photodynamic therapy, laser, and cryotherapy. The third, a 56-year-old woman with decreased visual acuity and epiretinal membrane, achieved stability and good visual outcomes after vitrectomy with cryotherapy. Conclusions: VPRTs pose diagnostic and therapeutic challenges given their heterogeneous presentations and potential for complications. Our cases illustrate that a multimodal management strategy – incorporating tailored combinations of therapies such as laser photocoagulation, cryotherapy, anti-VEGF injections, and surgery – is essential to address individual characteristics of each patient’s disease. Personalized treatment approaches allow for precise targeting of the lesions while minimizing risk of complications, contributing to better disease stabilization and visual outcomes. Early detection and tailored management are essential, though further research is needed to establish standardized treatment protocols. [ABSTRACT FROM AUTHOR]

Objectives: The objectives of this study were to evaluate the structural and functional outcomes after the loading phase with brolucizumab in switched patients with diabetic macular edema (DME) and to identify potential predictive biomarkers of treatment response. Methods: A total of 28 eyes with DME, switched to brolucizumab, were retrospectively reviewed. Main outcomes during the follow-up period, up to 6 weeks after the fifth injection, included changes in best-corrected visual acuity (BCVA), central subfield thickness (CST), macular volume, subfoveal choroidal thickness, intraretinal and subretinal fluid (IRF and SRF), cyst dimension including maximal horizontal cyst diameter (MHCD), maximal vertical cyst diameter (MVCD), width-to-height ratio (WHR), foveal avascular zone (FAZ) dimension, and vessel density (VD). Results: At the last follow-up, BCVA was significantly improved (p = 0.003). Significant reduction of CST was demonstrated after each injection time point (p < 0.05), and a dry macula was detected in 64.3% of patients at the last follow-up. The WHR was 1.23 ± 0.46, and a negative correlation to final CST (p < 0.0001) was found. In FAZ and VD analysis, no significant variation was detected. At the last disease activity assessment, the treatment regimen was q12 in 64% of patients. Conclusions: Brolucizumab leads to anatomical and functional improvements in switched eyes affected by DME. WHR may represent a predictive biomarker of treatment response. [ABSTRACT FROM AUTHOR]

AbstractPurposeMethodsResultsConclusionsAge-related macular degeneration (AMD) is a chronic retinal disease that can lead to blindness. While the NLR family pyrin domain containing 3 (NLRP3) inflammasome is implicated in AMD, the specific roles of miR-21 and NLRP3 in AMD-related inflammation remain unclear. Therefore, this study aimed to investigate the roles of miR-21 and NLRP3 in blue light-induced neurodegeneration in the mouse retina.A mouse model of retinal light damage was established through three months of blue light exposure (BLE). The experimental groups comprised the Control (Ctrl), BLE, BLE + miR-nc, and BLE + miR-21 inhibitor groups. The microRNAs were administered via intravitreal injections once per week. After successful modeling, changes in visual function and retinal morphology were investigated by using electroretinography and hematoxylin and eosin staining, respectively. Photoreceptor apoptosis was assessed using the TdT-mediated dUTP nick-end labeling assay. Immunofluorescence was used to detect and locate microglia and NLRP3 expression in the mouse retina. The expression of miR-21, NLRP3, and downstream factors in the retinas of each group was measured using qRT-PCR and western blotting.In the BLE and BLE + miR-nc groups, there was a decrease in visual function and retinal thickness, an increase in retinal ganglion cell injury and photoreceptor cell apoptosis, and elevated microglia activity in the retina, as evidenced by their migration to the outer retinal layer. In addition, the expression of miR-21, NLRP3, and downstream factors was increased in the BLE and BLE + miR-nc groups compared to that in the control group. However, intravitreal injection of the miR-21 inhibitor reduced miR-21 expression in the retina and significantly inhibited the activation of the NLRP3 inflammasome, effectively alleviating retinal photodamage caused by BLE.This study indicates that miR-21 may mitigate blue-light-induced retinal neurodegeneration by reducing the activation of the NLRP3 inflammasome in the mouse retina. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate and compare the mycobacterial load using a mobile laminar airflow (LAF) device in an IVI-dedicated outpatient clean room (OCR) without ventilation systems and in a hospital-based operating theatre (HOT). Methods: This case–control study was conducted in 2 different settings: OCR and HOT during a series of intravitreal injections (IVIs). The Air Microbial analysis was performed using a Surface Air System instrument at three different moments during the IVI sessions in both settings: at the operative site (OS), four meters from the OS (DOS) and in the disinfection room (DR). Results: At the OS in the OCR, the microbial load was 20.33 ± 16.51 CFU/m3 at T-1; 1.00 ± 1.00 CFU/m3 at T0; 6.67 ± 6.03 CFU/m3 at T1; 10.00 ± 9.54 CFU/m3 at T2 and 4.33 ± 3.06 CFU/m3 at T3. At the OS in the HOT, the CFU were respectively 0.00 ± 0.00 at T0; 0.67 ± 0.58 at T1; 0.00 ± 0.00 at T2 and 0.00 ± 0.00 T3. Conclusions: This standardized sterile technique in an OCR setting, with a mobile LAF, reduces the microbial colonies to levels that are safe and comparable to those recorded in the HOT setting, thus potentially improving the safety of IVIs in an OCR setting. [ABSTRACT FROM AUTHOR]

Introduction: Bilateral hemorrhagic hypopyon, also known as candy cane hypopyon, is an extremely rare presentation which we report as a unique case in association with intraocular mantle cell lymphoma (MCL). Case Presentation: A 63-year-old white male presented with a 3-week history of conjunctival injection OS that was unresponsive to erythromycin ointment and topical steroids, in the setting of recently discovered diffuse lymphadenopathy and malaise. On presentation, he was found to have bilateral hemorrhagic hypopyon. Lymph node biopsy was diagnostic of MCL, and subsequent anterior chamber paracentesis confirmed intraocular MCL. The patient was put into remission with intravitreal rituximab injections, systemic chemotherapy, and external beam radiation. Conclusion: Cases of MCL with ocular involvement typically involve ocular adnexal structures, and seldom involve the uvea. Furthermore, this patient represents an extremely unusual case in his presentation with a hemorrhagic hypopyon. [ABSTRACT FROM AUTHOR]

The optical imaging agent TcapQ488 has enabled imaging of retinal ganglion cell (RGC) injury in vivo in rodents and has potential as an effective diagnostic probe for early detection and intervention monitoring in glaucoma patients. In the present study, we investigated TcapQ488 in non-human primates (NHPs) to identify labeling efficacy and early signals of injured RGC, to determine species-dependent changes in RGC probe uptake and clearance, and to determine dose-limiting toxicities. Doses of 3, 6, and 12 nmol of TcapQ488 were delivered intravitreally to normal healthy NHP eyes and eyes that had undergone hemiretinal endodiathermy axotomy (HEA) in the inferior retina. Post-injection fundus fluorescence imaging using a Spectralis imaging platform (Heidelberg Engineering) documented TcapQ488 activation in RGC cell bodies. Optical coherence tomography (OCT), slit-lamp examinations, intraocular pressure measurements, and visual electrophysiology testing were performed to monitor probe tolerability. For comparison, a negative control, non-cleavable, non-quenched probe (dTcap488, 6 nmol), was delivered intravitreally to a normal healthy eye. In normal healthy eyes, intravitreal injection of 3 nmol of TcapQ488 was well-tolerated, while 12 nmol of TcapQ488 to the healthy eye caused extensive probe activation in the ganglion cell layer (GCL) and eventual retinal nerve fiber layer thinning. In HEA eyes, the HEA procedure followed by intravitreal TcapQ488 (3 nmol) injection resulted in probe activation within cell bodies in the GCL, confined to the HEA-treated inferior retina, indicating cell injury and slow axonal transport in the GCL. However, in contrast to rodents, a vitreal haze that lasted 2–12 weeks obscured rapid high-resolution imaging of the fundus. By contrast, intravitreal TcapQ488 injection prior to the HEA procedure led to minimal probe labeling in the GCL. The results of the dTcap488 control experiments indicated that fast axonal transport carried the probe out of the retina after cell body uptake. No evidence of pan-retinal toxicity or loss of retino-cortical function was detected in any of the three NHPs tested. Overall, these data provide evidence of TcapQ488 activation, without toxicity, in NHP HEA eyes that had been intravitreally injected with 3 nmol of the probe. Compared to rodents, unexpectedly rapid axonal transport in the NHPs reduced the capacity to visualize RGC cell bodies and axons through the backdrop of an intravitreal haze. Nonetheless, although intravitreal clearance rates did not scale to NHPs, HEA-induced reductions in axonal transport enhanced probe visualization in the cell body. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions To assess clinical outcomes of cataract surgery in eyes treated with intravitreal injections for cystoid macular oedema (CMO) secondary to retinal vein occlusions (RVOs).Eyes receiving intravitreal injections for CMO secondary to RVOs that underwent cataract extraction were identified from the Fight Retinal Blindness! Registry and matched 1:1 by 9 parameters with phakic controls also receiving intravitreal injections for the same condition. VA change at 12 months, central subfield thickness (CST) and injection frequency before and after surgery were compared between the two groups. The effect of baseline features on the final VA including age, CST, treatment frequency among others was tested.We included 193 eyes that had cataract extraction (exposed) matched with 193 phakic eyes that did not have surgery (matched). VA (95%CI) changed by +9.9 (7, 12.8) letters in exposed eyes versus −2.4 (−4.1, −0.7) letters in matched eyes (p < 0.01). The mean [SD] VA at 12 months was similar in exposed and matched eyes [60.7 (23.0) vs. 61.1 (24.3) letters, respectively, p = 0.81]. The mean [SD] CST was similar between groups before and at surgery, but it was greater in exposed compared with matched eyes [353 (152) vs. 322 (123) μm, respectively, p = 0.03] 12 months after surgery. Exposed eyes received more injections [median (range)] than matched eyes during the 12 months after surgery [5 (3, 7) vs. 4 (1, 6), injections, p < 0.01].Cataract extraction delivered good visual outcomes in patients treated for CMO secondary to RVOs. More injections were required on average in the 12 months after surgery in eyes undergoing surgery compared to matched controls. [ABSTRACT FROM AUTHOR]

Invasive aspergillosis (IA) significantly increases mortality in critically ill patients in the ICU and its occurrence is closely related to immunocompromise. Dissemination of IA is easily misdiagnosed and mistreated due to its ability to invade multiple systems throughout the body and lack of typical clinical manifestations. In this case, a 25-year-old previously healthy woman was hospitalized with fulminant myocarditis and treated with veno-arterial extracorporeal membrane pulmonary oxygenation (VA-ECMO) support and intravenous acyclovir, high-dose methylprednisolone, and immunoglobulin. 6 days later, she was successfully weaned from VA-ECMO and underwent cardiac rehabilitation. On day 10, she developed a fever (Tmax 38.3°C) and an irritating cough and began to experience reduced vision over the right eye with eye pain, redness, photophobia, and tearing 2 days later. Administration of levofloxacin eye drops and tobramycin/dexamethasone eye ointment was ineffective. The patient was positive for serum Aspergillus galactomannan antigen. Positron emission tomography/computed tomography (PET/CT) scan showed multiple hypermetabolic cavitary nodules in both lungs (SUVmax3.6) and thickening of the ocular ring wall with hypermetabolism in the right eye (SUVmax3.2). Ophthalmologic examination revealed that her best-corrected visual acuity in the right eye was reduced to light perception with an intraocular pressure of 21 mmHg, and B-scan ultrasonography showed vitreous opacity and retinal edema with mild detachment in the right eye. Metagenomic next-generation sequencing (mNGS) identified a large number of Aspergillus fumigatus sequences in bronchoalveolar lavage fluid, blood, and aqueous humor from the right eye, supporting the diagnosis of pulmonary and ocular involvement due to disseminated IA. Vitrectomy, anterior chamber irrigation, combined with intravenous and intravitreal injections of voriconazole and liposomal amphotericin B eventually cured the patient. This case highlights the importance of early identification and intervention regarding disseminated IA in immunocompromised critically ill patients, especially in the presence of multiple organ involvement. [ABSTRACT FROM AUTHOR]

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 lOP of g 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 lOP in dogs with end-stage glaucoma. [ABSTRACT FROM AUTHOR]

Retinal diseases, leading to various visual impairments and blindness, are on the rise. However, the advancement of retinal gene therapies offers new hope for treatment of such diseases. Among different vector systems for conferring therapeutic genetic load to retinal cells, adeno-associated viruses (AAVs) have been most intensively explored and have already successfully gained multiple clinical approvals. AAV-based retinal gene therapies have shown great promise in treating retinal disorders, but usually rely on the heavily disruptive administration methods such as subretinal injection. This is because the clinically well-established, minimally invasive alternative of intravitreal injection (IVI) necessitates AAVs to traverse the retinal inner limiting membrane (ILM), which is hard to penetrate in higher eye models, like human or porcine eyes. Additionally, AAVs' natural transduction preference, known as tropism, is commonly not specific to cells of only one target retinal layer, which is another ongoing challenge in retinal gene therapy. This review examines strategies to overcome these obstacles with a focus on the potential of magnetic nanoparticles (MNPs) for improved retinal AAV delivery. [ABSTRACT FROM AUTHOR]

Purpose: Faricimab is a bispecific antibody that inhibits angiopoietin-2 and vascular endothelial growth factor-A action and has been approved for the treatment of neovascular age-related macular degeneration and diabetic macular edema. Clinical trials have demonstrated its favorable safety profile. This report presents a case of intra-ocular inflammation and occlusive retinal vasculitis following a second intravitreal injection of faricimab. Methods: A single case report was obtained from a tertiary referral center. Results: A 73-year-old Asian man diagnosed with polypoidal choroidal vasculopathy presented with decreased vision in the left eye (OS) 2 weeks after the second faricimab administration. In the fourth week after the second faricimab injection, swept-source optical coherence tomography (OCT) revealed hyperreflective dots in the vitreous cavity, indicating vitreous cells. Color fundus photography showed new-onset perivenular hemorrhages and pallor of the inferonasal retina OS, of which OCT revealed retinal inner layer thickening, suggestive of retinal arteriolar occlusions. Retinal fluorescein angiography revealed delayed filling of the inferior temporal vein. The patient was diagnosed with intraocular inflammation and occlusive retinal vasculitis OS associated with repeated intravitreal faricimab administrations. Intravitreal dexamethasone implant was used instead of faricimab at this visit. Conclusions: The findings of this case hint towards the potential risk of retinal occlusive events associated with intravitreal faricimab injections. [ABSTRACT FROM AUTHOR]

Purpose: Papillophlebitis is a rare condition, manifesting as CRVO in the young adults. We aim to present our experience in managing patients with papillophlebitis. Methods: Retrospective review of patients' medical files. Results: Included were seven patients with a mean presenting age of 24.86 ± 4.4 years and mean follow-up of 40.4 ± 50.5 months. No pre-existing systemic illness was reported by any patient. One patient was subsequently diagnosed to have Behçet disease and another patient was diagnosed with homozygous mutation to MTHFR C6771. On presentation, fluorescein angiograms showed diffuse vascular and optic disc leakage. Four patients presented with papillophlebitis-associated CME, for which they were treated with systemic steroids and intravitreal anti-VEGF injections. One patient showed full recovery. In 3 patients, due to the protracted course of papillophlebitis and refractory CME, adalimumab was added. All 3 patients eventually showed complete resolution of CME. Two of them eventually developed extensive peripheral capillary non-perfusion that was treated with panretinal photocoagulation. Three patients did not develop CME: In two patients, papillophlebitis resolved after a short course of prednisone while in the third patient, papillophlebitis resolved spontaneously. Mean ± SD presenting log MAR VA was 0.2 ± 0.32 and it was 0.057 ± 0.11 at the last follow-up. Conclusion: To the best of our knowledge, this is the first description that suggests a role for TNF-ɑ blockers in the management of patients with recalcitrant papillophlebitis and non-responsive CME. Further studies are needed in order to thoroughly investigate the molecular background of papillophlebitis and clinical outcomes associated with this class of medications. [ABSTRACT FROM AUTHOR]

Purpose: To study the effects of anti–VEGF injections on the prevalence of ocular hypertension (OHT), sustained elevated intraocular pressure (SE-IOP), and primary open-angle glaucoma (POAG) with age-matched controls. Methods: A retrospective case-control study was performed with neovascular age-related macular degeneration (AMD) or diabetic macular edema (DME) against a control group involving atrophic AMD or diabetic retinopathy (DR) without DME. Bevacizumab, ranibizumab, or a combination of both were used in the treatment group. OHT was defined as IOP> 21 mm Hg while SE-IOP was defined as IOP that increased by > 6 mmHg or was > 25 mm Hg on two or more visits, 30 days apart. Patients with a pre-existing history of glaucoma, vein occlusions, IVI steroids, and pars plana vitrectomy were excluded. Results: A total of 1312 eyes of 784 patients were included in the study. Using age-matched controls, the treatment and control group was further refined to 394 eyes of 224 patients compared to 340 eyes from 170 patients respectively. The mean age was 58.4 ± 8.7 for the control versus 58.8 ± 8.8 years for the treatment group. The average IOP was higher in the injection group compared to the control with 25.8 ± 9.3 versus 19.5 ± 5.1 mmHg respectively, P< 0.001. Significant increases in POAG (10.7% vs 2.9%, p< 0.01), OHT (67.0% vs 22.4%, p< 0.001), and SE-IOP (41.1% vs 7.6%, p< 0.001) were seen in the injection group compared to the age-matched control group. The rates of POAG and OHT were positively associated with the number of injections, R2=0.856, P< 0.01 and R2=0.749, P< 0.05, respectively. Conclusion: Compared to age-matched controls, patients treated with anti-VEGF agents demonstrated an increased rate of OHT, SE-IOP, and POAG which correlated with the number of IVIs. However, additional prospective studies are needed to determine if there is a true association between intravitreal anti-VEGF injections and glaucoma. [ABSTRACT FROM AUTHOR]

Purpose: To determine if demographic factors and calculated areas of nonperfusion (NP) and neovascularization (NV) on ultra-widefield (UWF) fluorescein angiography (FA) in the eyes of patients with diabetes are associated with treatment with intravitreal injections (IVIs), panretinal photocoagulation (PRP), and diabetic retinopathy (DR) progression. Patients and Methods: This retrospective, cross-sectional study included 363 patients (651 eyes) treated at the University of Michigan Kellogg Eye Center between January 2009 and May 2018. Eligible participants were 18 years or older diagnosed with diabetes who received UWF FA. Patients with previous PRP or poor-quality images were excluded. Main outcome measures included comparison analyses of measured surface areas in millimeters squared (mm2) of total and regional retinal nonperfusion and neovascularization, number of IVIs and PRP treatments, and DR progression. Results: Our cohort received 3,041 IVIs and 878 PRP treatments with a mean follow-up of 915 days (SD ± 714). IVIs were positively associated with posterior NP (difference, 1.15 mm2; 0.43– 1.86; P= 0.0017). PRP treatments were positively associated with total NP (difference, 27.24 mm2; 14.68– 39.79; P< 0.001) and total NV (difference, 1.75 mm2; 0.84– 2.65; P< 0.001), as well as regional areas. While progression was not associated with NP/NV area, it was positively associated with a pre-existing diagnosis of type 2 as compared to type 1 diabetes (147% increase; 7– 373% increase; p=0.03). Conclusion: Areas of NP and NV on UWF FA demonstrated associations with PRP and IVIs in DR patients. [ABSTRACT FROM AUTHOR]