Intravitreal Injection Therapy Research Articles

Full thickness macular hole after intravitreal brolucizumab injection in neovascular age-related macular degeneration.

To describe a case of full thickness macular hole after intravitreal brolucizumab injection in neovascular age-related macular degeneration, which has not been reported to date. A 65-year-old male patient received brolucizumab intravitreal injection therapy for neovascular macular degeneration of the right eye. He received multiple intravitreal anti-VEGF injections on a pro re nata regimen and developed a full thickness macular hole. Surgical treatment was performed with pars plana vitrectomy of the right eye. Full thickness macular hole was successfully treated. Although a full thickness macular hole following intravitreal brolucizumab injection is an uncommon complication, it requires caution.

In-vitro safety assessment of meropenem on human retinal pigment epithelium (RPE)

PurposeEndophthalmitis is a severe infection accompanied by inflammation that affects the anterior and posterior parts of the eye. It is typically treated with a combination of antibiotics that cover various microorganisms. However, retinal pigment epithelium (RPE) cells are highly susceptible to damage from intravitreal injection therapy. This study aimed to investigate the impact of clinically relevant concentrations of meropenem (alone or in combination with vancomycin) on the viability and inflammation of RPE cells. DesignIn-vitro Study. MethodsRPE cells from passages 5–7 were treated with different concentrations of meropenem (1/4x, x, and 4x; [x = 16 mg/L]), vancomycin (30 mg/L), and meropenem (x) plus vancomycin for 24 h. The morphology assessment and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay were performed to evaluate cytotoxicity due to drug treatment. Real-time PCR was used to measure the relative expression of apoptotic genes (BCL-2 and BAX) and inflammation biomarkers (IL-1b and IL-6). ResultsMeropenem (alone or in combination with vancomycin) did not have any significant effect on RPE cell morphology, density, and viability. Gene expression analysis confirmed these results, showing no significant changes in the BCL-2/BAX ratio in drug-treated RPE cells compared to controls. Treatment with meropenem significantly induced the expression of IL-1b at all studied concentrations. Additionally, at concentrations of x and 4x, it also significantly increased the expression of IL-6, which was dose-dependent. However, this effect was not observed with vancomycin alone or in combination with meropenem. ConclusionsThe results of this study suggest that meropenem, either alone or in combination with vancomycin, does not induce RPE cytotoxicity. There was an upregulation of IL-1b and IL-6 in meropenem monotherapy, the clinical implication of which should be elucidated in future in-vivo or clinical studies.

Intravitreal Aflibercept vs Laser Therapy for Retinopathy of Prematurity

Prospective long-term data after retinopathy of prematurity (ROP) treatment with anti-vascular endothelial growth factor injections vs laser therapy are scarce. The FIREFLEYE (Aflibercept for ROP IVT Injection vs Laser Therapy) next trial is prospectively evaluating the long-term efficacy and safety outcomes following ROP treatment with intravitreal aflibercept vs laser therapy. To evaluate 2-year ophthalmic and safety outcomes after 0.4-mg aflibercept injection or laser therapy in the 24-week randomized (2:1) FIREFLEYE trial (FIREFLEYE outcomes previously reported). This prospective nonrandomized controlled trial performed in 24 countries in Asia, Europe, and South America (2020-2025) follows up participants treated in the FIREFLEYE randomized clinical trial (2019-2021) through 5 years of age. Participants included children born very or extremely preterm (gestational age ≤32 weeks) or with very or extremely low birth weight (≤1500 g) who were previously treated with a 0.4-mg injection of aflibercept compared with laser therapy for severe acute-phase ROP. Data for the present interim analysis were acquired from March 18, 2020, to July 25, 2022. Complications of ROP treated at investigator discretion (no study treatment). Efficacy end points included ROP status, unfavorable structural outcomes, ROP recurrence, treatment for ROP complications, completion of vascularization, and visual function. Safety end points included adverse events and growth and neurodevelopmental outcomes. Overall, 100 children were enrolled (median gestational age, 26 [range, 23-31] weeks; 53 boys and 47 girls). Of these, 21 were Asian, 2 were Black, 75 were White, and 2 were of more than 1 race. At 2 years of age, 61 of 63 children (96.8%) in the aflibercept group vs 30 of 32 (93.8%) in the laser group had no ROP. Through 2 years of age, 62 of 66 (93.9%) in the aflibercept group and 32 of 34 (94.1%) in the laser group had no unfavorable structural outcomes. No new retinal detachment occurred during the study. Four children in the aflibercept group (6.1%) were treated for ROP complications before 1 year of age (2 had preexisting end-stage disease and total retinal detachment; 1 had reactivated plus disease; and 1 had recurrent retinal neovascularization not further specified). Most children were able to fix and follow a 5-cm toy (aflibercept group, 118 of 122 eyes [96.7%] among 63 children; laser group, 62 of 63 eyes [98.4%] among 33 children). High myopia was present in 9 of 115 eyes (7.8%) among 5 children in the aflibercept group and 13 of 60 eyes (21.7%) among 9 children in the laser group. No relevant differences in growth and neurodevelopmental outcomes by Bayley Scales of Infant and Toddler Development, Third Edition and Vineland Adaptive Behavior Scales, Second Edition were identified. In this nonrandomized follow-up of a randomized clinical trial comparing treatment of severe acute-phase ROP with 0.4-mg injection of aflibercept and laser, disease control was stable and visual function was appropriate in children through 2 years of age. No adverse effects on safety, including growth and neurodevelopment, were identified. These findings provide clinically relevant long-term information on intravitreal aflibercept injection therapy for ROP. ClinicalTrials.gov Identifier: NCT04015180.

Association between the response of intravitreal antivascular endothelial growth factor injection and systemic factors of diabetic macular edema

BackgroundThis study investigated the effects of systemic factors in response to intravitreal injections in patients with macular edema due to non-proliferative diabetic retinopathy (NPDR).MethodsWe retrospectively reviewed the medical records of patients treated with intravitreal injections for macular edema secondary to NPDR between January 2018 and January 2021. The patients were divided into three groups according to the injection response. When patients with diabetic macular edema showed 20µ or more reduction in central retinal thickness compared to baseline, they were classified as responsive group, and if not, they were classified as refractory group. The responsive group was further divided into the complete and incomplete response groups. Patients with complete disappearance of edema at seven months were classified as the complete response group, whereas those in which edema did not disappear were classified as the incomplete response group. The clinical characteristics of each group, including medical history, ophthalmic examination results, and laboratory examination results at the time of diagnosis, were analyzed.ResultsOf the 112 eyes (91 patients) that satisfied the inclusion criteria, 89 (77 patients) in the responsive group and 23 (14 patients) in the refractory group were included in the analysis. The responsive group was further divided into the complete (51 eyes) and incomplete (38 eyes) response groups. The refractory group had significantly higher glycated hemoglobin levels and significantly lower estimated glomerular filtration rates than the responsive group (p = 0.026 and p = 0.012, respectively). In the multivariate logistic regression analysis, both factors were found to be significant in predicting the degree of response (all p < 0.05). No factor showed a significant difference between the incomplete and complete response groups(all p > 0.05).ConclusionsIn macular edema caused by NPDR, low glomerular filtration rates and high glycated hemoglobin levels may be used as predictors of poor response to intravitreal injection therapy. In addition to blood glucose control, education should be provided regarding the need for the continuous monitoring of renal function.

One-Year Functional and Morphological Prognosis After Intravitreal Injection Treatments According to Different Morphological Patterns of Diabetic Macular Edema in Real-Life: MARMASIA Study Group Report No.13

ABSTRACT Purpose To evaluate the responses of different optical coherence tomography (OCT) patterns of diabetic macular edema (DME) to intravitreal injection therapy. Methods In this retrospective, comparative, and multicenter study, patients who had previously untreated DME, who received intravitreal ranibizumab (IVR) or aflibercept (IVA) and/or steroid treatment with the pro re nata (PRN) treatment regimen after a 3-month loading dose, and had a 12-month follow-up in the MARMASIA Study Group were included. Morphological patterns of DME were divided into four groups based on OCT features diffuse/spongious edema (Group 1), cystoid edema (Group 2), diffuse/spongious edema+subretinal fluid (SRF) (Group 3), and cystoid edema+SRF (Group 4). Changes in central macular thickness (CMT) and best-corrected visual acuity (BCVA) at months 3, 6, and 12, and the number of injections at month 12 were compared between the DME groups. Results 455 eyes of 299 patients were included in the study. The mean baseline BCVAs [Logarithm of the Minimum Angle of Resolution (logMAR)] in groups 1, 2, 3, and 4 were 0.54 ± 0.24, 0.52 ± 0.25, 0.55 ± 0.23, and 0.57 ± 0.27, respectively. There was no significant difference between the baseline mean BCVAs between the groups (p = .35). The mean BCVAs were significantly improved to 0,47 ± 0,33 in group 1, 0,42 ± 0,33 in group 2, 0,47 ± 0,31 in group 3, and 0,45 ± 0,43 at month 12. There was no significant difference between the groups in terms of BCVA change at month 12 (p = .71). The mean baseline CMTs in groups 1, 2, 3, and 4 were 387,19 ± 128,19, 447,02 ± 132,39, 449,12 ± 109,24, and 544,19 ± 178,61, respectively. At baseline, the mean CMT was significantly higher in Group 4 than in the other groups (p = .000). The mean CMTs were significantly decreased to 325,16 ± 97,55, 334,94 ± 115,99, 324,33 ± 79,20, and 332,08 ± 150,40 in four groups at month 12 respectively (p > .05). The groups had no significant difference in mean CMT at month 12 (p = .835). The change in CMT was significantly higher in Group 4 than in the other groups at month 12 (p = .000). The mean number of intravitreal anti-VEGF injections at month 12 was 4.51 ± 1.57 in Group 1, 4.63 ± 1.54 in Group 2, 4.88 ± 1.38 in Group 3, and 5.07 ± 1.49 in Group 4. The mean number of anti-VEGF injections in Group 1 and Group 2 was significantly lower than in Group 4 (p = 0,014 and p = 0,017). Conclusions In real life, there was no significant difference between the DME groups in terms of visual improvement at month 12. However, better anatomical improvement was achieved in Group 4 than in the other DME groups.

Perifoveal retinal thickness changes after intravitreal aflibercept injection for choroidal neovascularization in age-related macular degeneration

ObjectiveThere has been some concern that anti-vascular growth factor treatment accelerates the development of macular atrophy in eyes with neovascular age-related macular degeneration. During the treatment with aflibercept, the thickness of choroid may decrease. This may lead to photoreceptor death. The rod cells are more susceptible to atrophic changes than cones during the disease. We aimed to find any thickness changes in the perifoveal outer nuclear layer, where the highest density of rods is found, during the aflibercept intravitreal injection therapy. Materials and MethodsRetrospectively, forty-two patients who were treated for age-related macular degeneration with choroidal neovascularization were included in the study. After the first three loading doses, intravitreal injections were repeated every two months. Outer nuclear layer thicknesses were measured 2000 µm away from the center of the fovea with OCT, at a total of 20 points, located at 180 and 90°. The mean of these measurements was obtained before the treatment and 1 year after the therapy. Results were compared by using the Wilcoxon Rank Test. ResultsThe mean visual acuity was 1,11±0,287 logMAR at the beginning and increased to 0,53±0,32 LogMAR after. Perifoveal thickness was significantly reduced when compared with the thickness before the treatment (p = 0.039, p < 0.05). This result was also significantly lower than the control group thicknesses (p = 0.035, p < 0.05). ConclusionAnti-VEGFs can cause loss of phagocytic functions of RPE. The mechanism of the observed thinning of the ONL may be described as follows: VEGF emitted by the RPE normally helps to maintain the choriocapillaris. Thus, injecting an anti-VEGF intravitreally causes RPE atrophy, which leads to a decrease in the choroidal vascular index. This in turn causes first the rods, and later the cones, that are part of the outer nuclear layer, to start to die and disappear, hence the thinning of this layer. As aflibercept consists of parts of the extracellular domain of both the VEGFR1 and VEGFR2 receptors, that are held together by a human IgG1 backbone, this makes the binding of aflibercept to VEGF-A and VEGF-B stronger as compared to the binding of the previously used ranibizumab or bevacizumab (by nearly a factor 100 in the case of the most abundant isoform VEGF-A 165). Besides, aflibercept also binds very well to placental growth factor (PIGF), which is also associated with several ocular diseases.

A Case Report Intravitreal Anti VEGF Bevacizumab on Patient with Hypertension Retinopathy and Exudative Retinal Detachment

Introduction : To present a case of intravitreal anti VEGF bevacizumab function on patient with hypertension retinopathy and exudative retinal detachment.&#x0D; Case Illustration : A 29 years old man presented with chief complaint blurry vision with visual acuity 1/60 on both eyes. History of hypertension sinced one year ago and already got hemodialisa treatment twice a week sinced 6 months ago. Ophthalmic examination showed decreased vision on both eyes and posterior segment both eyes we can find macular star and papil edema. Patient had diagnosed with hypertension retinopathy scheie 4 and exudative retinal detachment both eyes.&#x0D; Discussion : Hypertension will cause blood vessels to become damage in the form of sclerosis, thickening of blood vessel walls, and plasma leakage. Hypertension retinopathy acts as predictor of systemic morbidity and mortality due to organ target damage. Regulating systemic disease like blood pressure to become normal will improve clinical signs of hypertension retinopathy. Administration of anti-VEGF intravitreal injection therapy like bevacizumab can improve permeability of blood vessels in retina and decreased volume of exudate in retina. Visual acuity for this patient will improve to become 4/60 for both eyes.&#x0D; Conclusion : Uncontrolled hypertension can lead to organ target damage, which one of that was eyes. Hypertension retinopathy can make complications like exudative retinal detachment if the blood pressure still uncontrolled. Management of exudative retinal detachment caused by hypertension retinopathy was giving intravitreal anti VEGF injection in eyes to repair breakdown of blood retinal barrier, and the blood pressure must be well controlled to maintain permeability of blood retinal barrier.

Clinical Risk Factors for Retinopathy of Prematurity Reactivation after Intravitreal Antivascular Endothelial Growth Factor Injection

To assess the rate and risk factors for reactivation of retinopathy of prematurity (ROP) after intravitreal injection (IVI) of antivascular endothelial growth factor (VEGF) agents. Infants who received IVI therapy between 2017 and 2022 were enrolled and divided into 2 groups: those with and without ROP reactivation. Information on ROP variables and patient variables were analyzed using multivariable logistic regression. A total of 114 infants with 223 eyes were enrolled in the study. The ROP reactivation rate was 11.4% of infants (9.9% of eyes). The mean duration of reactivation was 84±45days. Among the 223 eyes treated with IVI, reactivation rates were 6% for bevacizumab, 13.9% for aflibercept, and 22.2% for ranibizumab. A multivariable regression model showed that ranibizumab was an independent risk factor (OR 11.4, P=.008) for reactivation. Other risk factors included infants with periventricular leukomalacia (OR 13.8, P=.003), patent ductus arteriosus ligation (OR 10.7, P=.032), and infants who still required invasive mechanical ventilation on the day of IVI therapy (OR 7.0, P=.018). All anti-VEGF agents carry a risk of ROP reactivation, with the risk being greater with ranibizumab 0.25mg than with bevacizumab 0.625mg. Reactivation of ROP should be assessed vigilantly, especially in those infants with increased risks. Future research to determine the optimal anti-VEGF selection and dosage in high-risk infants is warranted.

A study of the relationship between cytokine levels and the response to anti-VEGF therapy in polypoid choroidal vasculopathy with different choroidal thicknesses.

Polypoidal choroidal vasculopathy (PCV) is an irreversible retinal choroidal disease. Individuals with PCV exhibit diverse baseline characteristics, including systemic characteristics, ocular traits, metabolic factor levels, and different responses to intravitreal anti-VEGF therapy. This study aims to investigate the pathogenesis of PCV by analyzing the systemic characteristics, ocular traits, and cytokine levels at baseline within a cohort of patients who exhibit different responses to anti-VEGF treatment. We conducted a retrospective analysis involving 80 eyes diagnosed with PCV. Patients were categorized into two groups based on responses to suboptimal intravitreal ranibizumab injection therapy: those with suboptimal responses and optimal responses. Aqueous humor samples were collected from the experimental eyes, and cytokine expression levels were assessed using cytometric bead array analysis. All subjects were further stratified into two groups according to the median choroidal thickness. Subsequently, logistic regression analysis and the ROC curve were employed to examine the relationship between cytokine expression levels, choroidal thickness, and anti-VEGF response. The results revealed that compared to the group of optimal anti-VEGF response, the choroid in the suboptimal response group exhibited a significantly greater thickness. Additionally, compared to the suboptimal anti-VEGF response group, the expression levels of VEGF and VCAM-1 were markedly lower observed in the optimal anti-VEGF response group, while TNF-α showed the opposite trend. Logistic regression analysis indicated that VEGF, VCAM-1, and TNF-α in the aqueous humor were independent risk factors for a suboptimal anti-VEGF response. After adjusting other risk factors, the risk of suboptimal anti-VEGF response decreased to 0.998-fold, 0.997-fold, and 1.294-fold. The AUC values for VEGF, VCAM-1, and TNF-α were determined to be 0.805, 0.846, and 0.897, respectively. Furthermore, the risk of VEGF, VCAM-1, and TNF-α were significantly associated with an increased risk of suboptimal anti-VEGF response after correction for risk factors in the thick choroid group. Our study demonstrated that PCV exhibits systemic and ocular characteristics variations based on different anti-VEGF responses. The levels of cytokines in aqueous humor were found to have a significant correlation with the anti-VEGF response in PCV. VEGF, VCAM-1, and TNF-α are potential targets for assessing treatment response in thick choroidal PCV.

Clinical Trials and Future Outlooks of the Port Delivery System with Ranibizumab: A Narrative Review.

The port delivery system (PDS) of anti-VEGF therapy provides continuous delivery of ranibizumab (RBZ). In October of 2021, the American Food and Drug Administration (FDA) approved the PDS with RBZ as a treatment option for neovascular age-related macular degeneration (nAMD). As the field of PDS with RBZ is progressing rapidly, this narrative review provides a much-needed overview of existing clinical trials as well as ongoing and upcoming trials investigating PDS with RBZ. The phase 2 LADDER trial reported that the mean time to first refill with RBZ PDS 100mg/ml was 15.8months (80% CI 12.1-20.6), and pharmacokinetic profiling revealed a sustained concentration of RBZ in serum and aqueous humor. Later, the phase3 ARCHWAY trial reported that PDS with RBZ (100mg/ml) refilled every 24weeks was non-inferior to monthly intravitreal injection (IVI) with RBZ (0.5mg) in patients with nAMD over 9months and 2years. However, patients with PDS had a higher rate of adverse events including vitreous hemorrhage and endophthalmitis. Patients indicate high treatment satisfaction with both PDS and IVI, but the lower number of treatments with PDS was reported as a preferred choice. Several ongoing and future clinical trials, of which details are discussed in this paper, are further exploring the potentials of PDS with RBZ. We conclude that the PDS provides continuous deliverance of RBZ and that clinical efficacy levels are non-inferior to IVI therapy for nAMD. Yet, a higher rate of adverse events remains a concerning detail for widespread implementation. Future studies are warranted to better understand which patients may benefit best from this treatment approach, if long-term efficacy can be sustained, and if safety of PDS can be further improved.

Retraction of cystoid macular edema from the fovea after intravitreal anti-VEGF therapy for birdshot chorioretinopathy.

To report the effect of anti-vascular endothelial growth factor inhibitor (anti-VEGF) on fovea-involving cystoid macular edema in a patient with Birdshot chorioretinopathy. A 42-year-old male patient presented to our hospital with bilateral posterior uveitis with retinal vasculitis, cystoid macular edema and optic disc edem a. He was diagnosed with birdshot chorioretinopathy based on clinical appearance and tissue type HLA-A29. The patient underwent vitrectomy in the right eye without any change in visual acuity. Retinal leakage was reduced by oral prednisolone, which could not be tapered below 50 mg per day without relapse. Oral prednisolone, topical dexamethasone and subtenonal kenalog were associated with intraocular pressure rise in both eyes. Hence, his uveitis responded to steroids, but there was no detectable effect of any steroid-sparing immunomodulatory drugs. The patient had been on oral prednisolone 50 mg for five years when it was decided to attempt intravitreal VEGF inhibitor injection therapy. The anti-VEGF therapy diminished cystoid macular edema in the fovea and improved the visual acuity. Here we report for the first time the long-term outcomes of anti-VEGF injections on fovea-involving cystoid macular edema in Birdshot chorioretinopathy to keep steroid at the minimal possible doses and preserve a satisfying visual acuity level.

Comparing the Optical Coherence Tomography Outcomes of Intravitreal Injection Anti Vascular Endothelial Growth Factor in Branch Retinal Vein Occlusion (BRVO)

Background: BRVO is a blockage of the branches of the retinal vein due to a thrombus. The prevalence of 10-year BRVO is 1.6 per 100 subjects. The effect of anti-VEGF injection on BRVO management is effective in improving visual acuity and reducing macular oedema.&#x0D; Case presentation: A man, 32 years old, presented to the ophthalmology clinic at the Dr. M. Djamil General Hospital with a chief complaint of blurred vision in his left eye 1 week before admission. The blurred vision began suddenly. Visual acuity in LE was 20/50 and did not advance with a pinhole. Funduscopic examination of LE showed clear media, rounded papillae with well-defined borders, blood vessels aa:vv = 1:3, venous tortuosity (+) increased in the inferotemporal quadrant; retina: Bleeding (+) with dot blot and flame-shaped inferiorly, exudate (+) cotton wool spots at the inferotemporal region; foveal reflex (+)↓ on the macula. OCT LE examination showed macular intraretinal hypo-reflection and macular thickening with a central macular thickness of 617 μm. The physical examination showed a body weight of 114.9 kg, a height of 173 cm, and a body mass index of 38.4. Within 5 months after 3 times administrations of intravitreal injections of anti-VEGF bevacizumab and ranibizumab, visual acuity of LE: 20/25 was obtained, and increased appearance of the retinal fundus and OCT LE.&#x0D; Conclusion: Intravitreal injection therapy of anti-VEGF bevacizumab and ranibizumab is effective in reducing macular oedema and restoring visual acuity in BRVO.

Potential of TAK-593 ophthalmic emulsion for the treatment of age-related macular degeneration.

Intravitreal injection therapy of anti-VEGF antibody or steroids is the mainstream for patients with age-related macular degeneration (AMD). However, since intravitreal injection is invasive administration, side effects such as endophthalmitis are major problems. In this study, we selected eye drops as a non-invasive treatment method, and aimed to develop eye drops that can deliver TAK-593 (VEGF receptor tyrosine kinase inhibitor) to the posterior segment of the eye.Since TAK-593 is a poorly water-soluble drug, the TAK-593 emulsion was formulated. The solubility of TAK-593 in various oils was measured, and the oil used for the emulsion was selected. Furthermore, viscosity enhancers were added to the emulsion in order to improve the drug delivery into the eye.As viscosity enhancer, xanthan gum was selected based on the properties and the viscosity of the emulsion. The delivery of TAK-593 to the posterior eye was increased by the formulation concentration and the addition of viscosity enhancers.In the laser-induced choroidal neovascularization model, TAK-593 emulsion eye drops showed the same angiogenesis-suppression efficacy as anti-VEGF antibody intravitreal injection. From these results, it was revealed that TAK-593 with an effective drug concentration can be delivered to the posterior eye by non-invasive eye drop administration.

Long-term Outcomes of Myopic Choroidal Neovascularization and Retinal Changes according to ATN Classification

Purpose: To evaluate the clinical outcomes of myopic choroidal neovascularization (CNV) and atrophic and tractional changes according to the ATN (A: atrophy, T: traction, N: neovascularization) classification system.Methods: This was a retrospective review of the medical records of myopic CNV patients treated with intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections and followed up for at least 3 years. Atrophic and tractional components were graded according to the ATN system at baseline and the last visit.Results: The study included 21 eyes in 21 patients. The mean age was 52.29 ± 14.6 years, the mean follow-up duration was 57.65 ± 18.8 months, and the mean number of injections was 2.9 ± 1.9. Recurrence occurred in seven eyes (33.3%). Five patients (23.8%) developed myopic CNV in the contralateral eye. The mean initial and final logarithm of the minimum angle of resolution (logMAR) visual acuities were 0.44 ± 0.30 and 0.33 ± 0.39, respectively. Visual acuity was maintained or improved compared to baseline in 15 eyes (71.4%). Baseline visual acuity was significantly associated with the final visual acuity (&lt;i&gt;p&lt;/i&gt; = 0.026). Based on the ATN classification system, the atrophic component progressed in four eyes (19.0%), while the tractional component improved in one eye (4.8%) and progressed in five eyes (23.8%).Conclusions: Intravitreal anti-VEGF injection therapy effectively preserved long-term vision in myopic CNV patients. Evaluation of the atrophic and tractional components should not be neglected during the follow-up.

Benefit of intravitreal injections in patients with sub-threshold baseline visual acuity: a retrospective single-centre study

PurposeTo investigate the lower visual acuity threshold for recommending intravitreal injection therapy (IVI). The lower limit of 1.3 logMAR best-corrected visual acuity (BCVA) was adopted in 2006 and has been maintained since then.MethodsIn this retrospective study, data from patients with a logMAR BCVA ≤ 1.3 and 24 months follow-up were analysed. We included patients with neovascular age-related macular degeneration (nAMD), diabetic macular oedema (DME), or retinal vein occlusion (RVO).ResultsThe data from 164 patients (nAMD: 107; DME: 15; RVO: 42) were analysed. We observed a significant improvement at all time intervals (0 to 6, 6 to 12, 12 to 18, and 18 to 24 months after initiating IVI) compared to baseline. Across all indications, median BCVA improved from 1.4 to 1.0 within the first 6 months and remained stable within 24 months. Patients received a median of 5 and 10 injections within 6 and 24 months, respectively. Median foveal retinal thickness was 594.5 μm at baseline and dropped to 244.5 μm, 235.5 µm, 183 µm, and 180 µm during the four consecutive time intervals.ConclusionPatients with nAMD, DME, and RVO with poor baseline BCVA may also benefit from intravitreal therapy with VEGF-inhibitors. In the present study, we observed functional and morphological improvement over 2 years irrespective of the underlying macular disease. Those patients should not be excluded from therapy.

Informed consent research at a tertiary hospital: How impactful is competency in simpler versus standard consent forms for intravitreal injection therapy?

&lt;b&gt;Aim: &lt;/b&gt;To compare the impact of competency in intravitreal injection therapy (IVIT)-related simpler versus standard consent forms (CFs).&lt;br /&gt; &lt;b&gt;Material and methods: &lt;/b&gt;Four hundred patients scheduled for IVIT in a tertiary hospital were enrolled between April 1, 2022 and June 30, 2022. These patients were eligible for the study if they had their first IVIT in one eye; those scheduled for IVIT in the other eye were not. Data, including age, gender, educational level, whether the patient was admitted alone or with a companion, and prior IVIT status were collected. A trained clinic secretary first gave the patients the commonly used standard CFs, followed by simpler CFs.&lt;br /&gt; &lt;b&gt;Results: &lt;/b&gt;The mean age was 66.10±9.90 years. 93.80% had previously received IVIT. 53.80% of the patients consented on their own. While 98.00% consented without reading standard CFs, 56.00% consented after reading simpler CFs (p&amp;lt;0.001). The need for IVIT-related extra information and the desire against having IVIT were significantly higher in simpler than standard CFs (p&amp;lt;0.001). 5.00% of those who approved IVIT without reading both forms were illiterate, and 29.20% had vision issues. The probability of simpler CF reading increased by 4.653 and 7.510 times in high school and university graduates, respectively, relative to primary school graduates.&lt;br /&gt; &lt;b&gt;Conclusion: &lt;/b&gt;Simpler CFs had a much higher reading rate, which was linked to a higher rate of patients opting against IVIT. In medical fields like ophthalmology, where many procedures and research are performed, ethically approved informed consent requires consideration of patients' education and prior treatment experience.

Impact of intravitreal injection therapy on contrast sensitivity in patients with nAMD and DME

PurposeThe study aims to evaluate changes in contrast sensitivity (CS) during therapy with intravitreal vascular endothelial growth factor (VEGF) inhibitors in patients with neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME).MethodsProspective, uncontrolled, multicenter study on patients with neovascular AMD or DME who underwent intravitreal injection therapy with Ranibizumab, Aflibercept, or Bevacizumab was conducted. Best corrected visual acuity (BCVA) and CS measured by Mars Letter Contrast Sensitivity Test (MLCS) and Freiburg Visual Acuity and Contrast Test (FrACT) in logCS were evaluated before 3 consecutive VEGF inhibitor injections, which followed the pro renata regimen in treatment-naïve and pretreated eyes with a maximum of 9 injections. Correlation of MLCS and FrACT was calculated by the Spearman’s rank correlation coefficient.ResultsEighty eyes of 74 patients (mean age 72.7; SD ± 9.96) were included. BCVA improved significantly from 0.44 (SD ± 0.21) logMAR to 0.38 (SD ± 0.23) logMAR by 0.06 (SD ± 0.14) logMAR values (p < 0.001). CS measured by MLCS increased significantly from 1.27 (SD ± 0.25) logCS to 1.39 (SD ± 0.22) logCS (p < 0.001). CS measured by FrACT also improved significantly from 1.22 (SD ± 0.32) logCS to 1.30 (SD ± 0.29) logCS (p = 0.035). A positive correlation between MLCS and FrACT was found (r = 0.389; p < 0.001). Despite statistical significance, results for BCVA, MLCS, and FrACT failed clinical significance. Overall best test results were achieved with MLCS.ConclusionsIntravitreal injection therapy with VEGF inhibitors led to an improvement of BCVA and CS measured by MLCS and FrACT. MLCS was superior and more sensitive compared to FrACT and even BCVA to evaluate CS in elderly patients with macular pathology.

Candida Lusitaniae Endophthalmitis: A Brief Literature Review with a Focus on Treatment Options

Intraocular fungal infections are uncommon. They may originate either exogenously, as occurs with penetrating trauma and postoperative infections, or endogenously, through hematogenous spread. Patients at the highest risk of endogenous endophthalmitis are those with central venous catheters, total parenteral nutrition, and active intravenous drug use, as well as those who are immunosuppressed [1]. Candida species are the most common fungi identified from endogenous sources related to the above. Although the incidence of ocular involvement is unclear, a few studies provide a range of 2.2–16% in patients with candidemia [2,3]. Non-albicans species of candida infections are very rare. In particular, C. lusitaniae is found in only approximately 1% of patients with candida blood stream infections [4]. Treating candida ophthalmologic infections usually requires expertise of both ophthalmology and infectious diseases. Patients who have evidence of only chorioretinitis should be treated with systemic antifungal agents. Intravitreal injection in combination with systemic antifungals is recommended for patients with infections involving the macula or vitreous humor. Vitrectomy along with intravitreal injection and systemic antibiotic therapy is needed for patients with heavy vitritis [5]. The duration of treatment is decided on a case-by-case basis but typically consists of four to six weeks of systemic antifungal therapy.

Transition from Laser to Intravitreal Injections for Diabetic Retinopathy: Hospital Utilization and Costs from an Extended Healthcare Perspective.

Purpose: To describe the trends in hospital utilization and economic outcomes associated with the transition from laser to intravitreal injection (IVI) therapy for diabetic retinopathy (DR) at Oslo University Hospital (OUH), which provides the largest retina service in Norway. Methods: This descriptive study analyzed hospital administrative data and determined the average utilization and treatment proportions of laser therapy, IVIs and vitrectomy for each patient per year. The Chi-square test was used to compare resource use between treatment groups. From an extended healthcare perspective, the annual cost per patient was calculated using Norwegian tariff data from 2020 and the National Medication Price Registry for patients seen between 2010 and 2018. Bootstrapping was performed to generate 95% confidence intervals for the cost per patient per year. Results: Among the 1838 (41% female) patients treated for DR between 2005 and 2018, OUH provided on average 1.09 laser treatments per DR patient and 0.54 vitrectomies per DR patient in 2005, whose utilization declined to 0.54 and 0.05 treatments per DR patient, respectively, by 2018. Laser treatments declined from 64% to 10%, while vitrectomies declined from 32% to 1%. In contrast, IVI treatments increased from 4.5% to 89% of the total share, representing an average increase, from 0.08 injections per patient in 2005 to 4.73 injections per patient in 2018. Both the increasing number of DR patients and the shift in the type of treatment increased the economic costs of treating DR from a total of EUR 0.605 million (EUR 2935 per patient) in 2010 to EUR 2.240 million (EUR 3665 per patient) in 2018, with IVIs contributing considerably to these costs. Conclusions: Despite the decline in the use of vitrectomies, the transition from laser to IVI therapy for DR increased the healthcare resource utilization and economic costs of its treatment over the observed time. A main cost driver was the need for long-term IVIs, in addition to the drug cost itself. Trade-offs can be achieved through effective alternative IVI delivery or appropriate drug choice that balances patient needs with the economic burden of treating DR.

Long-Term Visual Outcomes in Exudative Age-Related Macular Degeneration Patients With Unanticipated Gaps in Therapy.

This study's objective was to describe long-term visual outcomes of patients with age-related macular degeneration (AMD) treated with intravitreal anti-vascular endothelial growth factor injections who were lost to follow-up and then resumed treatment with anti-vascular endothelial growth factor injections. This was a retrospective cohort study of eyes with at least 7 years of follow-up following the initiation of treatment for wet AMD with and without gaps in therapy. The baseline mean logMAR visual acuity was 0.65 ± 0.5 (Snellen acuity 20/89) in eyes with gaps in therapy and 0.53 ± 0.3 (20/68) in eyes without gaps. In the initial 7-year follow-up period, the eyes with gaps in therapy had significantly worse visual acuity (P < .001) and this remained significant when accounting for baseline visual acuity (P < .001). Gaps in intravitreal injection therapy for exudative AMD were negatively associated with visual acuity. Adherence to therapy is important to address in the care of patients with exudative AMD. [Ophthalmic Surg Lasers Imaging Retina 2022;53:481-489.].