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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]

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]

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]

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]

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]

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]

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]

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]

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]

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 evaluate visual and anatomical outcome of consecutive patients who received intravitreal injections (IVI) of faricimab for the treatment of neovascular age-related macular degeneration (nAMD). Patients and methods: A retrospective study of patients treated for nAMD with one to three IVIs of faricimab from October 2022 to January 2024. Demographic data, treatment history, best corrected visual acuity (BCVA), anatomic parameters, and adverse events (AEs) were collected. Results: After one IVI of faricimab, previously treated (n=160) eyes with a mean of 33.51 IVIs and treatment-naïve (n=10) eyes showed a mean BCVA gain of +0.59± 0.52 letters (p=0.364) and +5.00± 6.50 letters (p=0.461), respectively, and a mean central subfield thickness (CST) reduction of − 27.65± 5.33 μm (p< 0.001) and − 94.10± 39.74 μm (p=0.042), respectively. In treatment-refractory eyes after switching from aflibercept (n=108), mean BCVA increased by +0.42± 0.66 (p=0.745) and the mean CST improved by − 21.98± 6.04 (p< 0.001). After three IVIs of faricimab previously treated (n=106) and treatment-naïve (n=5) eyes showed a mean BCVA increase of +1.57± 0.88 letters (p=0.051) versus +12.50± 8.14 letters (p=0.185), and a mean CST reduction of − 25.51± 5.82 μm (p< 0.001) versus − 82.60± 36.20 μm from baseline, respectively. In treatment-refractory eyes after switching from aflibercept (n=79), mean BCVA improved by +2.15± 1.08 letters (p=0.029) and mean CST decreased by − 27.46± 7.04 μm (p< 0.001). Mean pigment epithelial detachment (PED) was also significantly reduced even between the first and the third faricimab injection in previously treated eyes (p=0.03). The proportion of eyes with intraretinal fluid and subretinal fluid improved significantly in all eyes and treatment-refractory eyes after switching from aflibercept. Ocular AEs were reported in three out of 170 eyes, and one patient had two stroke events during faricimab therapy. Conclusion: Three IVIs of faricimab have the potential to improve visual acuity and anatomical parameters even in treatment-refractory nAMD eyes with a mean dosing interval of more than 6 weeks. [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]

Background: The prevalence of vision-threatening diseases, such as age-related macular degeneration (AMD) and diabetic macular edema (DME), is likely to increase in developed countries owing to an aging population, rising life expectancy, and unfavorable lifestyle changes. Increases in the burden of vision-threatening diseases pose a challenge to the healthcare system. After the emergence of intravitreal anti-VEGF inhibitors, treatment options for neovascular AMD (nAMD), DME, retinal vein occlusion (RVO) and myopic choroidal neovascularization (myopic CNV) have increased. As this change in treatment practices has occurred over the last two decades, it is important to demonstrate changes in patient numbers and administered treatments to provide solutions for handling the workload and productivity in ophthalmology departments. In addition, the registry data landscape has evolved in Finland in recent years. Thus, understanding the possibilities and limitations of ophthalmology registries and patient information systems is required. Methods: This study involved the secondary use of retrospectively registered data from the data warehouse of the Hospital District of Southwest Finland. Our goal was to explore how the workload of ophthalmology departments caused by intravitreal injections has evolved from 2015 to 2022. Results: The ophthalmology department workload increased significantly during our observation period as the total number of patients receiving intravitreal treatments for nAMD, DME, RVO, and myopic CNV increased 199.6% from 2015 to 2021. In addition, the total number of administered anti-VEGF injections increased during our observation period, but the increase rate began to subside (2019– 2020: increase 23.7%, 2020– 2021: increase 10.3%, 2021– 2022: increase 6.7%). Conclusion: Supporting the utilization of registry data is essential in evidence-based discussions evolving workload in healthcare. However, it is important to understand the limitations and the quality of the registries. Our study contributes to better understanding the Finnish registry perspective, and it demonstrates the increase in workload in ophthalmology departments caused by intravitreal injections. [ABSTRACT FROM AUTHOR]

Objective: This investigation was to determine the relationship between changes in the expression levels of miR-134 and the E2F transcription factor 6 (E2F6) in mediating control of apoptosis in N-methyl-D-aspartate (NMDA)-induced glaucomatous mice. Methods: Morphological and structural changes were quantitatively analyzed along with apoptosis in the retinal ganglion cell (RGC) layer, internal plexiform layer and RGCs. Glaucomatous RGCs were transfected, and cell viability and apoptosis were examined. The targeting relationship between miR-134 and E2F6 was analyzed, as well as their expression pattern. Results: Intravitreal injection of NMDA induced a significant reduction in the number of RGCs and thinning of IPL thickness. miR-134 was highly expressed and E2F6 was lowly expressed in glaucoma mice. Suppression of miR-134 or E2F6 overexpression inhibited apoptosis in the glaucomatous RGCs and instead their proliferative activity. MiR-134 targeted inhibition of E2F6 expression. Suppressing rises in E2F6 expression reduced the interfering effect of miR-134 on glaucomatous RGC development. Conclusion: Depleting miR134 expression increases, in turn, E2F6 expression levels and in turn reduces glaucomatous RGC apoptosis expression. [ABSTRACT FROM AUTHOR]

Objectives: To report the occurrence of the regression of the flow signal from the neovascular network in macular neovascularizations (MNVs), developing in the context of age-related macular degeneration (AMD), treated with faricimab in a treat-and-extend regimen. Methods: Eyes affected by AMD-related MNV and treated with faricimab intravitreal injections in a treat-and-extend (TE) regimen were consecutively retrospectively screened in five specialized retina centers. Changes in neovascular network characteristics during the course of the treatment were analyzed. The availability of high-quality optical coherence tomography angiography (OCTA) at the beginning of the treatment and at the regression of the MNV was necessary for inclusion. According to greatest linear diameter (GLD) changes during treatment, eyes were divided into three groups: a complete regression (CR) group, a partial remission (PR) group (a reduction of at least 50% of the GLD from baseline to last follow-up), and a stable group (stable/showing a reduction lower than 50% of the GLD from baseline to follow up). Results: One hundred and ten (110) eyes were included. The CR group was composed of 12 eyes (10.9%), while the PR group represented 60.9% of the study population. CR occurred after a mean of 6.0 ± 1.4 months, ranging from 4 to 8 months. Time to regression was significantly lower in eyes naïve to treatment before the study compared with the others (p = 0.022). A significantly lower baseline GLD was detected in the CR group (1292.2 ± 195.6 μm) compared with the PR group (1324.6 ± 135.6 μm) and the stable group (1412.5 ± 110.9 μm) (omnibus p = 0.003). Conclusions: Complete regression of the flow signal from the MNV neovascular network documented with OCTA may occur during TE regimens with faricimab. In treatment-naïve eyes, regression occurs earlier during the treatment. [ABSTRACT FROM AUTHOR]

Background/Objectives: Neovascular age-related macular degeneration (nAMD) is a retinal disorder leading to irreversible central vision loss. The pro-re-nata (PRN) treatment for nAMD involves frequent intravitreal injections of anti-VEGF medications, placing a burden on patients and healthcare systems. Predicting injections needs at each monitoring session could optimize treatment outcomes and reduce unnecessary interventions. Methods: To achieve these aims, machine learning (ML) models were evaluated using different combinations of clinical variables, including retinal thickness and volume, best-corrected visual acuity, and features derived from macular optical coherence tomography (OCT). A "Leave Some Subjects Out" (LSSO) nested cross-validation approach ensured robust evaluation. Moreover, the SHapley Additive exPlanations (SHAP) analysis was employed to quantify the contribution of each feature to model predictions. Results: Results demonstrated that models incorporating both structural and functional features achieved high classification accuracy in predicting injection necessity (AUC = 0.747 ± 0.046, MCC = 0.541 ± 0.073). Moreover, the explainability analysis identified as key predictors both subretinal and intraretinal fluid, alongside central retinal thickness. Conclusions: These findings suggest that session-by-session prediction of injection needs in nAMD patients is feasible, even without processing the entire OCT image. The proposed ML framework has the potential to be integrated into routine clinical workflows, thereby optimizing nAMD therapeutic management. [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: To examine the potential protective effects of adipose-derived mesenchymal stem cell-derived extracellular vesicles (ASC-EVs) on ARPE-19 cells exposed to hydrogen peroxide (H2O2) stress and to evaluate their ability to delay retinal degeneration in Royal College of Surgeons (RCS) rats. Methods: ARPE-19 cells were pre-treated with ASC-EVs for 24 h, followed by exposure to 200 μM H2O2 for an additional 24 h. RCS rats received an intravitreal injection of phosphate-buffered saline in one eye and ASC-EVs in the other eye. Results: ASC-EV pretreatment significantly protected against H2O2 in the Cell Counting Kit-8 assay and was also effective in the lactate dehydrogenase-release assay. It notably reduced early apoptosis (Annexin V-fluorescein isothiocyanate/propidium iodide assay) and late apoptosis (Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling assay), while significantly decreasing intracellular reactive oxygen species, glutathione levels, and superoxide dismutase activity. NFE2L2, HMOX1, and NQO1 mRNA levels, along with Nrf2, HO-1, and NQO1 protein levels, were significantly elevated with ASC-EV pretreatment. Compared with ARPE-19-derived EVs, 11 miRNAs were upregulated and 34 were downregulated in ASC-EVs. In RCS rats, intravitreal injections of ASC-EVs led to significant preservation of the outer nuclear layer and photoreceptor segments, along with increased nuclear Nrf2 expression and elevated HO-1 and NQO1 levels in the inner retina. Eyes that received intravitreal injections of ASC-EVs demonstrated significantly preserved electroretinography a- and b-wave amplitudes at 1 week post-injection, though this effect faded by 2 weeks. Conclusions: ASC-EVs mitigated apoptosis and oxidative stress in ARPE-19 cells subjected to H2O2 exposure and temporarily slowed retinal degeneration in RCS rats via Nrf2 pathway activation by miRNAs. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the anatomic and visual outcomes and safety profile of initial Indian eyes with neovascular age-related macular degeneration (nAMD) treated with intravitreal injection (IVI) of brolucizumab. Methods: This retrospective multicentric, real-world study enrolled consecutive eyes with nAMD that were treated with IVI brolucizumab after it was launched in India in October 2020. Data collected for each eye included best-corrected visual acuity (BCVA), central subfield thickness (CSFT), subretinal fluid (SRF), and intraretinal fluid (IRF) status at 6, 12, and 24 months follow-up. Also recorded were the lens status, treatment protocol, number of injections received before enrollment (in switch-over cases), total number of injections, and adverse effects noticed during the study period. Primary outcomes were change in BCVA, CSFT at follow-up visits, and incidence of intraocular inflammation (IOI). Secondary outcomes were profile of macular neovascularization, treatment protocols, mean number of injections, and maximum injection-free interval observed in eyes treated by pro-re-nata (PRN) protocol. Results: In total, 331 eyes received a mean of 3.55 ± 1.83 injections. Most frequent treatment protocol was PRN (53%). BCVA data was available for 100%, 96%, and 74% eyes at 6, 12, and 24 months follow-up. BCVA and CSFT improved significantly (P < 0.001) at all follow-ups. Two hundred and seventy-six (83.38%) out of 331 eyes received more than one injection; out of these, 241 (87.3%) eyes that were treated by PRN protocol could achieve mean "maximum injection-free interval" of 19.43 ± 8.82 weeks. IOI and retinal vasculitis were reported in 2.11% (7/331) and 0.60% (2/331) eyes, respectively. None of the eyes with IOI or vasculitis lost any vision at the final follow-up. Conclusion: This study demonstrated favorable visual and anatomic outcomes and safety profile for eyes with nAMD treated by IVI brolucizumab. Mean maximum injection-free interval in eyes treated with PRN was 19 weeks. [ABSTRACT FROM AUTHOR]

Purpose: Targeted drug delivery to the optic nerve head may be useful in the preclinical study and later clinical management of optic neuropathies, however, there are no FDA-approved drug delivery systems to achieve this. The purpose of this work was to develop an optic nerve head drug delivery technique. Methods: Different strategies to approach the optic nerve head were investigated, including standard intravitreal and retroorbital injections. A novel SupraChoroidal-to-Optic-NervE (SCONE) delivery was optimized by creating a sclerotomy and introducing a catheter into the suprachoroidal space. Under direct visualization, the catheter was guided to the optic nerve head. India ink was injected. The suprachoroidal approach was performed in New Zealand White rabbit eyes in vivo (25 animals total). Parameters, including microneedle size and design, catheter design, and catheter tip angle, were optimized ex vivo and in vivo. Results: Out of the candidate optic nerve head approaches, intravitreal, retroorbital, and suprachoroidal approaches were able to localize India ink to within 2 mm of the optic nerve. The suprachoroidal approach was further investigated, and after optimization, was able to deposit India ink directly within the optic nerve head in up to 80% of attempts. In eyes with successful SCONE delivery, latency and amplitude of visual evoked potentials was not different than the naïve untreated eye. Conclusions: SCONE delivery can be used for targeted drug delivery to the optic nerve head of rabbits without measurable toxicity measured anatomically or functionally. Successful development of this system may yield novel opportunities to study optic nerve head-specific drug delivery in animal models, and paradigm-shifting management strategies for treating optic neuropathies. Translational Relevance: Here we demonstrate data on a new method for targeted delivery to the optic nerve head, addressing a significant unmet need in therapeutics for optic neuropathies. [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]

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). Phase 1, open-label, single-center, first-in-human clinical study. Adult patients (≥50 years of age) with GA secondary to AMD in the study-treated eye (treated eye) with Snellen best-corrected visual acuity 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 best-corrected visual acuity of 20/800 or better in fellow, nontreated eye were included. Patients (n = 17) were enrolled sequentially into low-dose (3.56 × 1010 viral genome/eye; n = 3), intermediate-dose (1.07 × 1011 viral genome/eye; n = 3), and high-dose (3.56 × 1011 viral genome/eye; n = 11) cohorts without steroid prophylaxis and assessed for safety and tolerability over 24 months. Safety and tolerability outcomes included assessment of ocular and nonocular treatment-emergent adverse events (AEs) over 24 months. Secondary outcomes included GA lesion size and growth rate. Baseline patient characteristics were consistent with the disease under study, and all enrolled patients demonstrated foveal center–involved GA. JNJ-81201887 was well-tolerated across all cohorts, with no dose-limiting AEs. No serious or systemic AEs related to study intervention occurred. Overall, 5 of 17 patients (29%) experienced 5 events of mild ocular inflammation related to study treatment; examination findings in all resolved, and AEs resolved in 4 of 5 patients after 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. Geographic atrophy 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 through 6 to 0.056 mm at months 18 through 24. All 3 studied doses of JNJ-1887 showed a manageable safety profile through 24 months of follow-up. Further investigation of JNJ-1887 for the treatment of GA is warranted. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. [ABSTRACT FROM AUTHOR]

Purpose: To report the incidence of post‐injection endophthalmitis (PIE) and the cumulative risk associated with repeated injections of intravitreal anti‐vascular endothelial growth factor (anti‐VEGF). Methods: We employed nationwide registries in Denmark to include all individuals aged ≥40 years who received at least one intravitreal anti‐VEGF injection in 2007–2022. Our primary endpoint PIE was identified using specific diagnostic codes for endophthalmitis and procedure codes for vitreous biopsy within 10 days prior to and 120 days post‐injection. Patients were stratified according to the underlying diagnoses for which they received the treatment. The relative risk (RR) for PIE was calculated between groups based on the number of injections received by the patients. Results: We identified 60 825 patients who received intravitreal anti‐VEGF treatment during study time, with a median age of 77.2 years and females constituting 58.1%. We identified 232 cases of PIE after 1 051 549 injections during follow‐up, resulting in an incidence of 0.022% [95% CI 0.019%–0.025%]. Despite a linear growth in annual anti‐VEGF use, the incidence remained stable at 0.020% [95% CI 0.017%–0.023%] from 2013 to 2022. Compared to patients receiving 1–3 injections, RR for patients receiving 4–20, 21–40, and >40 injections were 0.46 [95% CI 0.34–0.63], 0.32 [95% CI 0.21–0.50], and 0.54 [95% CI 0.36–0.81], respectively. Findings were similar across the different diagnoses. Conclusions: Based on 16 years of nationwide registry data, this study identified a low and stable incidence of PIE. Notably, the highest risk of endophthalmitis was within the first three anti‐VEGF injections. [ABSTRACT FROM AUTHOR]

Background and Purpose: Retinal ganglion cells (RGCs) are the output stage of retinal information processing, via their axons forming the optic nerve (ON). ON damage leads to axonal degeneration and death of RGCs, and results in vision impairment. Nerve growth factor (NGF) signalling is crucial for RGC operations and visual functions. Here, we investigate a new neuroprotective mechanism of a novel therapeutic candidate, a p75‐less, TrkA‐biased NGF agonist (hNGFp) in rat RGC degeneration, in comparison with wild type human NGF (hNGFwt). Experimental Approach: Both neonate and adult rats, whether subjected or not to ON lesion, were treated with intravitreal injections or eye drops containing either hNGFp or hNGFwt. Different doses of the drugs were administered at days 1, 4 or 7 after injury for a maximum of 10 days, when immunofluorescence, electrophysiology, cellular morphology, cytokine array and behaviour studies were carried out. Pharmacokinetic evaluation was performed on rabbits treated with hNGFp ocular drops. Results: hNGFp exerted a potent RGC neuroprotection by acting on microglia cells, and outperformed hNGFwt in rescuing RGC degeneration and reducing inflammatory molecules. Delayed use of hNGFp after ON lesion resulted in better outcomes compared with treatment with hNGFwt. Moreover, hNGFp‐based ocular drops were less algogenic than hNGFwt. Pharmacokinetic measurements revealed that biologically relevant quantities of hNGFp were found in the rabbit retina. Conclusions and Implications: Our data point to microglia as a new cell target through which NGF‐induced TrkA signalling exerts neuroprotection of the RGC, emphasizing hNGFp as a powerful treatment to tackle retinal degeneration. [ABSTRACT FROM AUTHOR]

This report details an uncommon occurrence of chronic endophthalmitis following cataract surgery attributed to an infection by Trichosporon inkin (T. inkin). The infection was identified through MALDI-TOF mass spectrometry along with sequencing analysis. Although the patient exhibited a robust immune response, the infection escalated quickly from the right eye to the left. Treatment involved vitrectomy and peeling surgery on the right eye, paired with systemic fluconazole antifungal therapy and intravitreal injection, resulting in significant recovery. The visual acuity of the right eye enhanced from finger counting to 20/63. This account represents the inaugural documented instance of endophthalmitis caused by T. inkin that was effectively managed with fluconazole. This underscores the critical role of vitreous humor enrichment culture and antifungal susceptibility testing of T. inkin in the treatment of endophthalmitis. [ABSTRACT FROM AUTHOR]

Purpose: The study aimed to investigate the effects of blood glycated hemoglobin (HbA1c) and mean platelet volume (MPV) levels in patients with diabetic macular edema who received a dexamethasone implant (DEXI). Methods: Twenty-two Type 2 diabetic patients with pre-existing HbA1c and MPV measurements before injection were selected for the study. These patients received an intravitreal DEXI injection. Optical coherence tomography images and medical records before and after the injection were evaluated retrospectively. Results: The mean visual acuity level before and after the injection was 0.21±0.1 and 0.30±0.09, respectively. The median values for patient age, HbA1c, and MPV were 65 years, 7.4, and 10.6, respectively. There was no statistically significant difference in visual acuity levels and foveal macular thickness changes before and after the injection between groups with MPV levels above and below 10.6 (p>0.05). In addition, there was no statistically significant difference in visual acuity changes before and after the injection between patients under and over 65 years of age (p>0.05). There was also no statistically significant difference in foveal macular thickness changes before the injection between patients under and over 65 years of age (p>0.05). However, a statistically significant decrease in central macular thickness was observed after the injection in patients under 65 years of age compared to those over 65 years of age (p<0.05). Conclusion: MPV and HbA1c values have been shown to be markers of inflammation and poor disease control in diabetic patients. Our study indicates that there is no correlation between the response to DEXI injection and MPV or HbA1c values. [ABSTRACT FROM AUTHOR]

Background/Objectives: To evaluate the impact of intravitreal bevacizumab (IVB) therapy on anatomical and visual outcomes in patients with macular neovascularization (MNV) secondary to chronic central serous chorioretinopathy (cCSC). Methods: This retrospective observational study reviewed the medical records of treatment-naïve patients diagnosed with cCSC complicated by MNV and treated with IVB injections over a 5-year period. The presence of MNV was confirmed using optical coherence tomography angiography (OCTA). Best-corrected visual acuity (BCVA), subfoveal choroidal thickness (SFCT), and subretinal fluid (SRF) were recorded pre- and post-IVB treatment. Results: Twenty-two eyes of 22 patients (mean age, 68 ± 11 years) were included. After a mean follow-up of 21.0 ± 14.6 months, SRF significantly decreased from baseline (176.86 ± 115.62 µm) to the final follow-up (80.95 ± 87.32 µm, p = 0.003). A greater SRF reduction was associated with more injections (>7) (p = 0.047). However, no significant changes were observed in BCVA (p > 0.05) or SFCT (p > 0.05), irrespective of follow-up duration or injection frequency. Complete resolution of SRF was achieved in nine patients (40.9%), and a significantly greater reduction in SFCT was observed in complete responders compared to non-responders (p = 0.03). Conclusions: IVB therapy significantly reduced SRF in cCSC patients with secondary MNV, though it did not lead to visual improvement or significant changes in SFCT. However, greater choroidal thinning in patients with complete fluid resorption may suggest distinct underlying mechanisms or alternative sources of subretinal fluid beyond the MNV itself. [ABSTRACT FROM AUTHOR]

Purpose: Intravitreal drug administration has become the gold standard for the treatment of many retinal diseases, including age-related macular degeneration (AMD), diabetic retinopathy (DR) and retinal vein occlusion (RVO). The frequency of this procedure has increased significantly after the introduction of anti-VEGF drugs, since the rise in the average age of the population, which is closely correlated with these diseases. In order to ensure therapeutic success in these patients with chronic retinal diseases, intravitreal treatment with anti-VEGF requires a long-term maintenance regimen with repeated administrations. For this reason today, we must consider the risks linked to complications associated with the long-term application of this therapy. Our study aims to investigate whether the intravitreal injection of anti-VEGF may lead to damage to the corneal endothelium, either directly through the administration procedure or indirectly due to the drug's toxicity. We aimed to establish a clear correlation between intravitreal drug administration and a statistically significant reduction in corneal endothelial cell count in the treated eye when compared to the untreated eye. The study also sought to assess whether different toxicities might be present between different types of drugs belonging to the same anti-VEGF family. Materials and Methods: The study was conducted by examining a cohort of 133 patients suffering from different diseases: AMD, EMD and RVO. All patients underwent measurement of the endothelial count with CellChek® 20, considering the value measured at the first injection as time zero and reassessed at each subsequent treatment session. The measurement of the endothelial count was performed both on the eye under treatment (TE) and in the eye not undergoing intravitreal injection (NTE) with anti-VEGF drugs for each injection cycle. Different anti-VEGF drugs such as Bevacizumab, Ranibizumab, Aflibercept, Brolucizumab were used for intravitreal therapy. The test patients were included in a 12-month follow-up programme, in which the measurement intervals are dictated by the treatment plan. Results: The statistical analysis performed on the corneal endothelial cell counts showed that the ECD (endothelial cell density) parameter decreases with each administration of the drug. The analysis of the difference in the mean endothelial cell counts of the TE reveals that the difference in the number of endothelial cells between the first and second counts in TE is 54.00; greater than the difference in the number of cells found in NTE, which was 13.42. Both the difference between the TE and NTE cell counts are statistically significant. In the case of the TE, the p-value is <0.001, while in the case of the NTE the p-value is still significant as <0.05. The hypothesis that the different types of anti-VEGF drugs could determine the decrease in endothelial cell count differently was also evaluated. No statistically significant data emerged from the analyses (p-value is >0.05). Conclusions: The study demonstrated a statistically significant reduction of corneal endothelial cells in patients undergoing intravitreal injection treatment per number of injections with anti-VEGF, this reduction being independent of the type of anti-VEGF used (Bevacizumab, Ranibizumab, Aflibercept and Brolucizumab). [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy and safety of intravitreal chlorhexidine (CHX) for sterilising the vitreous cavity in bacterial endophthalmitis. Methods: For in-vitro experiments, full-thickness retina explants were harvested from freshly enucleated pig eyes. Six-millimeter circular sensory retina patches were then incubated in varying concentrations of CHX (0.625-800 µg/mL) for 24 hours. Retinal cell viability was determined at the end of the incubation period with a live-dead assay. The bactericidal effects of the tested CHX concentrations were determined using a quantitative suspension test on Staphylococcus epidermidis. The safety of CHX was also tested by injecting varying doses of CHX (50-400 µg/mL) into the vitreous cavity of albino rabbits followed by flash electroretinography (ERG) and light microscopy. The bactericidal effect of the non-toxic CHX doses was determined using the rabbit model of endophthalmitis created by injecting 3000 CFU/0.1 mL of Staphylococcus epidermidis. Results: In vitro concentrations of CHX greater than 6.25 µgr/mL exerted a bactericidal effect, while concentrations of CHX less than 200 µg/mL did not impair retinal cell viability. Intravitreal concentrations of CHX between 20-100 µg/mL were adequate to sterilise the infected rabbit vitreous cavity in the animal model. No significant functional or anatomical deleterious effect was observed with ERG or light microscopy. Conclusion: CHX can sterilise the vitreous cavity in an animal model of bacterial endophthalmitis without impairing retinal cell viability. Our results encourage further research for clinical use of chlorhexidine in treatment of bacterial endophthalmitis. [ABSTRACT FROM AUTHOR]

Background and Objective: Retinal gliovascular proliferation (RGVP) is a benign lesion of the retina that can arise idiopathically or secondary to another disease entity. This study describes the clinical features, treatment, and outcomes of six patients with secondary RGVP associated with irradiated, regressed retinoblastoma, and distinguishes it from late local relapse of retinoblastoma. Patients and Methods: In a retrospective review of available clinical records of 550 patients evaluated for retinoblastoma in a single ocular oncology practice between 1975 and 2022, seven eyes of six patients were identified as having secondary RGVP overlying a treated and regressed retinoblastoma. The clinical features, treatment, and outcomes are described. Results: The median age at RGVP diagnosis was 20 years. All RGVPs were associated with a completely regressed retinoblastoma and in proximity to a calcific tumor residue or chorioretinal atrophy that remained after external beam radiotherapy (six eyes) or plaque brachytherapy (one eye). Lesions were measured between 2.8 to 12 mm in largest basal diameter and 1.3 to 4.4 mm in thickness and described as globular, raised areas with focal retinal telangiectasis often associated with overlying subretinal fluid or hemorrhage. Median time between initial retinoblastoma treatment and detection of RGVP was 20 years. Treatment was decided based on evidence of lesion growth and most often consisted of laser photocoagulation and intravitreal anti-VEGF injection. Through available follow-up of the treated lesions, all exhibited at least partial regression, while two untreated lesions remained stable, reassuring us against late local relapse of retinoblastoma. Conclusions: Secondary RGVP develops occasionally in association with regressed previously irradiated retinoblastoma. This lesion must be distinguished from late local relapse of active retinoblastoma. [Ophthalmic Surg Lasers Imaging Retina 2024;55:714–720.] [ABSTRACT FROM AUTHOR]