Intravitreal Therapy Research Articles

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

<b>Aim: </b>To compare the impact of competency in intravitreal injection therapy (IVIT)-related simpler versus standard consent forms (CFs).<br /> <b>Material and methods: </b>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.<br /> <b>Results: </b>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<0.001). The need for IVIT-related extra information and the desire against having IVIT were significantly higher in simpler than standard CFs (p<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.<br /> <b>Conclusion: </b>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.

Bevacizumab (Avastin) in treatment of maculopathy secondary to Proliferative Diabetic Retinopathy (PDR) in Afghanistan

Objective: To investigate the efficacy of intravitreal anti-VEGF therapy in the treatment of maculopathy secondary to Proliferative Diabetic Retinopathy (PDR) in Afghanistan.

Novel Approaches in the Drug Development and Delivery Systems for Age-Related Macular Degeneration

The number of patients with ocular disorders has increased due to contributing factors such as aging populations, environmental changes, smoking, genetic abnormalities, etc. Age-related macular degeneration (AMD) is one of the common ocular disorders which may advance to loss of vision in severe cases. The advanced form of AMD is classified into two types, dry (non-exudative) and wet (exudative) AMD. Although several therapeutic approaches are explored for the management of AMD, no approved therapy can substantially slow down the progression of dry AMD into the later stages. The focus of researchers in recent times has been engaged in developing targeted therapeutic products to halt the progression and maintain or improve vision in individuals diagnosed with AMD. The delivery of anti-VEGF agents using intravitreal therapy has found some success in managing AMD, and novel formulation approaches have been introduced in various studies to potentiate the efficacy. Some of the novel approaches, such as hydrogel, microspheres, polymeric nanoparticles, liposomes, implants, etc. have been discussed. Apart from this, subretinal, suprachoroidal, and port delivery systems have also been investigated for biologics and gene therapies. The unmet potential of approved therapeutic products has contributed to several patent applications in recent years. This review outlines the current treatment options, outcomes of recent research studies, and patent details around the novel drug delivery approach for the treatment of AMD.

Associations with Non-Persistence with Intra-Vitreal Therapy for Neovascular Age-Related Macular Degeneration at 24 Months

Aims: The aim of the study was to investigate non-persistence with treatment for neovascular age-related macular degeneration (NvAMD) before day 720 (24 months) after initiation, explore associations with baseline characteristics and variation between sites. Methods: Anonymised demographic and clinical data were extracted from electronic medical records at treating National Health Service (NHS) Trusts for NvAMD eyes starting intra-vitreal therapy from 2017 to 2018. Time to non-persistence with treatment, defined as no recorded attendance for either monitoring or treatment for a period ≥6 months, was visualised with a Kaplan-Meier survival plot. Associations with treatment non-persistence were investigated using a Cox proportional hazards model. Results: Analysis included 7,970 eyes of 7,112 patients treated at 13 NHS trusts. Censoring deaths and those eyes in which treatment was stopped permanently, the Kaplan-Meier analyses demonstrated survival figures of 77.7% for persistence with treatment to day 360 and 71.8% to day 720. Hazard ratios for non-persistence with treatment were reduced at 10 sites, relative to the reference, with first-treated eye status and with baseline acuity worse than or equal to LogMAR 1.0. Hazard ratios increased with younger age, in the presence of other ocular co-morbidities and with baseline acuity better than or equal to LogMAR 0.5. After an episode of non-persistence, visual acuity decreased by at least 0.1 and 0.3 LogMAR in 39% and 18% of eyes, respectively. Conclusions: Non-persistence with treatment was common, especially in the first year of treatment, and was often associated with a decrease in visual acuity. Treatment site, baseline visual acuity, and age were the strongest predictors of treatment non-persistence before day 720. Understanding and addressing reasons for non-persistence are important to ensure that effective but expensive treatments are used cost-effectively and to maintain acuity. Variation in non-persistence between sites, even after adjustment for other variables, suggests that local factors in treatment provision may be particularly important.

Coats' Disease in a Patient With Cornelia de Lange Syndrome: Management With Laser and Bevacizumab.

Cornelia de Lange syndrome is a congenital disorder with multisystem abnormalities including multiple ocular findings. The authors report a case of Coats' disease in a patient with Cornelia de Lange syndrome who was successfully treated with laser and intravitreal bevacizumab. This case demonstrates the importance of fluorescein angiography in making the diagnosis and directing treatment and the efficacy of combined laser with intravitreal anti-vascular endothelial growth factor therapy for persistent vascular leakage associated with Coats' disease in Cornelia de Lange syndrome. [J Pediatr Ophthalmol Strabismus. 2023;60(4):e45-e48.].

AN ATYPICAL RETINAL VASCULITIS, ANEURYSMS AND NEURORETINITIS IRVAN: RARE CASE REPORT AND MANAGEMENT

Idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN) syndrome is a rare and progressive disorder that predominantly affects both the eyes of young female individuals and can threaten visual function. Peripheral ischemia and macular exudation are regular ndings in patients. The treatment options include panretinal photocoagulation (PRP), systemic immunosuppression,and intravitreal antiangiogenic and corticosteroid therapy. Here we are presenting a case of old chronic IRVAN presenting as recurrent epiretinal membrane. Patient was underwent ERM removal and Dexamethasone implant to prevent recurrence in this case.

Intravitreal enzyme replacement therapy to prevent retinal disease progression in children with neuronal ceroid lipofuscinosis type 2 (CLN2): Interim safety report

Intravitreal enzyme replacement therapy to prevent retinal disease progression in children with neuronal ceroid lipofuscinosis type 2 (CLN2): Interim safety report

Real-World Experience Using Intravitreal Brolucizumab Alone or in Combination with Aflibercept in the Management of Neovascular Age-Related Macular Degeneration.

To evaluate real-world experience using intravitreal brolucizumab (IVBr), alone or in combination with aflibercept, in eyes with neovascular age-related macular degeneration (nAMD) treated previously with other inhibitors of VEGF (anti-VEGF). This was a retrospective study of all eyes with nAMD treated with IVBr on a treat-and-extend protocol at a single center. Best-corrected visual acuity (BCVA), optical coherence tomography (OCT) at baseline and final visit, and drug-related adverse events were analyzed. Eyes with recurrent macular fluid on IVBr every 8 weeks were treated with a combination therapy alternating between IVBr and aflibercept every month. Among 52 eyes (40 patients) on IVBr, all had been previously treated with other anti-VEGF therapy, with 73% having persistent macular fluid. After a mean follow-up of 46.2±27.4 weeks on IVBr, the mean treatment interval for intravitreal therapy increased to 8.8±2.1 weeks on IVBr from a baseline of 6.1±3.1 weeks (p<0.001). Macular fluid decreased and BCVA was stable/improved in 61.5% of eyes on IVBr. Ten eyes with increased macular fluid on IVBr monotherapy when extended to every 8 weeks were treated with combination therapy alternating between IVBr and aflibercept every 4 weeks. In these eyes, 80% had improved macular fluid on OCT and 70% stable or improved BCVA after a median follow-up of 53 weeks on combination therapy. Mild intraocular inflammation developed in four eyes, all occurring on IVBr monotherapy, and none had associated vision loss. In the real world, IVBr used to treat eyes with nAMD previously treated with other anti-VEGF therapies appears to be well tolerated and associated with an improvement in macular fluid, stabilization of BCVA, and/or increase in intravitreal treatment interval. Combination therapy alternating between IVBr and aflibercept monthly appears to be well tolerated and can be considered for eyes with macular fluid on IVBr every 8 weeks.

Central serous chorioretinopathy: A review.

Central serous chorioretinopathy (CSC) is the fourth most common non-surgical retinopathy associated with fluid leakage. The pathogenesis is not yet completely understood, but changes in the choroid, sclera and RPE have been described associated with venous congestion of choroidal outflow. CSC can be categorised into acute, chronic, and recurrent subtypes with recent classifications of simple and complex based on the area of RPE change seen on fundus autofluorescence. A multimodal imaging approach is helpful in the diagnosis and management of CSC and secondary complications such as type 1 neovascularisation. Although spontaneous resolution with relatively good visual outcomes is common, treatment should be considered in patients with persistent or recurrent SRF. Treatment options include laser, systemic medications, intravitreal therapy, and surgery. Of these, argon laser for focal extramacular fluid leaks and photodynamic therapy of leakage identified by indocyanine-green angiography currently have the greatest supportive evidence.

Addition of fenofibrate to statins is associated with risk reduction of diabetic retinopathy progression in patients with type 2 diabetes and metabolic syndrome: A propensity-matched cohort study

AimThis study aimed to determine the association between fenofibrate added to statin therapy and diabetic retinopathy progression. MethodsIn this propensity-matched study using the Korean National Health Insurance Service cohort (2002–2019), patients with type 2 diabetes and metabolic syndrome (≥ 30 years) receiving statin therapy were matched 1:2 by propensity score into the statin plus fenofibrate group (n = 22,395) and statin-only group (n = 43,191). The primary outcome was a composite of diabetic retinopathy progression including vitreous hemorrhage, vitrectomy, laser photocoagulation, intravitreous injection therapy and retinal detachment. ResultsThe median (quartiles) follow-up duration was 44.0 (27.6–70.6) months. For the primary outcome, the incidence rate per 1,000 person-years was 9.66 in the statin-only group and 8.68 in the statin-plus-fenofibrate group. The risk of the primary outcome was significantly lower (hazard ratio [HR]=0.88; 95% confidence interval [0.81;0.96] P = 0.005) in the statin-plus-fenofibrate group than in the statin-only group. Only patients with pre-existing retinopathy showed benefits from fenofibrate treatment (HR=0.83 [0.73;0.95] P = 0.006). In addition, the statin plus fenofibrate group exhibited significantly lower risks of vitreous hemorrhage (HR= 0.86 [0.75;0.995] P = 0.042), laser photocoagulation (HR=0.86 [0.77;0.96] P = 0.009) and intravitreous injection therapy (HR=0.73 [0.59;0.90] P = 0.003) than those in the statin-only group. There was no significant interaction between the different characteristics at baseline and the treatment effect. ConclusionThe addition of fenofibrate to statins was associated with significantly lower risk of diabetic retinopathy progression than statin therapy alone in patients with type 2 diabetes and metabolic syndrome.

Brolucizumab in Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema: Ophthalmology and Diabetology Treatment Aspects.

Anti-vascular endothelial growth factor (anti-VEGF) therapies have become the standard of care in the treatment of neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME), resulting in a remarkable decrease in disease-related vision loss. However, the need for regular injections places a significant burden on patients, caregivers, and the healthcare system and improvements in vision may not be maintained long term. As a result of its drying potency and duration of action, brolucizumab, an intravitreal anti-VEGF therapy approved for the treatment of nAMD and DME, could decrease injection frequency for patients and provide an efficacious treatment; however, balancing its benefits and risks can be challenging. There have been reports of intraocular inflammation (IOI) in patients treated with brolucizumab, which, if left untreated, may result in severe vision loss. Recent evidence, however, indicates that early recognition of IOI and prompt and aggressive systemic corticosteroid treatment in response to posterior segment involvement can lead to favorable outcomes in these relatively rare but severe cases. A series of consensus meetings were conducted in 2022 between Swiss medical retina experts and diabetologists, discussing the current data for brolucizumab and exploring various challenges to its use, including the associated risk of IOI. The outcome is a collation of practical insights and guidance for ophthalmologists on the use of brolucizumab in patients with nAMD and DME, including patient selection and assessment, treatment regimen and monitoring, and the recognition and management of adverse events.

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.

Influence of Intravitreal Therapy on Choroidal Thickness in Patients with Diabetic Macular Edema

This study aimed to analyze the variation in subfoveal choroidal thickness (SFCT) and its relationship with the variation in central macular thickness (CME) in response to intravitreal therapy with an antiangiogenic (anti-VEGF) drug or corticosteroid in type 2 diabetic patients with diabetic macular edema (DME). This retrospective study included 70 eyes of 35 patients: 26 eyes received 4-5 intravitreal injections of aflibercept, 26 eyes were treated with a single intravitreal implant injection of dexamethasone, and 18 eyes without DME did not receive intravitreal therapy. SPECTRALIS® optical coherence tomography (OCT) (Heidelberg Engineering, Heidelberg, Germany) was used to measure the SFCT and CME before and at the end of the follow-up period. The mean reductions in CME were 18.8 +/- 14.7% (aflibercept) and 29.7 +/- 16.9% (dexamethasone). The mean reductions in SFCT were 13.8 +/- 13.1% (aflibercept) and 19.5 +/- 9.6% (dexamethasone). The lowering effects of both parameters were significantly greater in the group treated with the dexamethasone implant (p = 0.022 and p = 0.046 for CMT and SFCT, respectively). Both therapies significantly decreased both CME and SFCT, independent of factors such as age, sex, previous intravitreal therapy, antidiabetic treatment, and the time of diabetes progression. There were no changes in the mean values of CME and SFCT in the untreated eyes. SFCT significantly decreased in response to intravitreal therapy with anti-VEGF or corticosteroids, irrespective of age, sex, previous intravitreal therapy, antidiabetic treatment, and the time of diabetes progression. There was a correlation between the changes in CME and SFCT after intravitreal therapy with aflibercept or dexamethasone implantation. SFCT was not a good predictor of the CME response but could be used to monitor the response to treatment. Local intravitreal therapy only affected the treated eye.

The Impact of Residual Retinal Fluid Following Intravitreal Anti-Vascular Endothelial Growth Factor Therapy for Diabetic Macular Edema and Macular Edema Secondary to Retinal Vein Occlusion: A Systematic Review

The association between residual retinal fluid and visual acuity for diabetic macular edema (DME) and macular edema (ME) secondary to retinal vein occlusion (RVO) is not well established. We conducted a systematic literature search for peer-reviewed articles reporting on visual acuity stratified by subretinal fluid (SRF), intraretinal fluid (IRF), or any retinal fluid at final follow-up after intravitreal anti-vascular endothelial growth factor therapy injection for treatment of DME or ME secondary to RVO. Two observational studies on ME secondary to RVO and one study for DME found no significant differences between eyes with and without residual retinal fluid for final BCVA. One randomized controlled trial (RCT) found that eyes with residual retinal fluid had significantly worse final best-corrected visual acuity in ME secondary to RVO, whereas another RCT found no significant difference for DME. There is a paucity of evidence examining the impact of residual retinal fluid on visual acuity in DME and ME secondary to RVO. The limited evidence suggests that aggressive fluid resolution is worthwhile. [Ophthalmic Surg Lasers Imaging Retina 2023;54:50-58.].

HEMOGLOBIN C TRAIT PRESENTING WITH BILATERAL CENTRAL RETINAL VEIN OCCLUSION.

To report a case of bilateral sequential, central retinal vein occlusion (CRVO) in a man with newly diagnosed hemoglobin C trait. A 67-year-old man presented with a one-month history of declining visual acuity. He was diagnosed with left CRVO. Bilateral temporal retinal ischemia and arteriovenous anastomoses on fluorescein angiography suggestive of sickle cell retinopathy prompted a systemic work-up. Hemoglobin electrophoresis revealed an underlying hemoglobin C trait. Six-months after his initial presentation, the patient developed symptomatic right CRVO. The initial left CRVO was complicated by optic disc swelling and macular edema. Intravitreal antiangiogenic therapy was initiated and the macular edema resolved. The left eye subsequently developed an epiretinal membrane which was surgically removed. Macular edema in the right eye also resolved after intravitreal antiangiogenic therapy. This is the first reported case of bilateral CRVO in a case of hemoglobin C trait. It is possible that erythrocyte inflexibility, caused by hemoglobin C-induced dehydration and crystallization, acted concomitantly with hypertension to produce occlusive microangiopathy. This case highlights the need for further investigation in patients presenting with central retinal vein occlusion, especially when bilateral, or when retinal angiography reveals bilateral pathology.

Medications Damaging Vascular Bed or Causing Microvasculopathy / Occlusion-3: Pathogenesis, Diagnosis, and Treatment (Intraocular Gentamicin, Tobramycin, Amikacin, Vancomycin, Moxifloxacin)

Retinal vascular occlusion and vascular bed injury are rare but serious complications after eye and periocular surgery. History of cardiovascular disease, retrobulbar injection, perioperative high intraocular pressure and drug toxicity have been reported as possible causative factors. Intracameral antibiotic administration during cataract surgery has been adopted by almost all ophthalmologists in the world and has been routinely applied. Intravitreal antimicrobial administration has advanced the treatment of intraocular infections. Being able to bypass the blood-ocular barriers allows high drug concentrations to be delivered directly to the posterior segment with minimal systemic absorption. However, intravitreal therapy may be associated with risks of ocular toxicity, as the difference between therapeutic and toxic doses of some antimicrobial drugs falls within a narrow concentration range.

Panophthalmitis After Aurolab Aqueous Drainage Implant (AADI) in Refractory Glaucoma with Vogt-Koyanagi-Harada Syndrome (VKH): A Case Report

This case of Vogt-Koyanagi-Harada (VKH) disease underwent Aurolab Aqueous Drainage Implant (AADI) for refractory glaucoma. Later, developed postoperative (2 months) panophthalmitis characterized by sudden visual loss, moderate pain, redness, and purulent discharge. Systemic, topical, and intravitreal antibiotic therapy was started immediately, and evisceration was performed.

Subfoveal choroidal thickness before and after intravitreal Ranibizumab injection in patients with choroidal neovascularization

Background: Ranibizumab is anti-vascular endothelial growth factor (anti-VEGF) agent made for intraocular use, like smaller antibody fragment that can penetrate retina. Intravitreal ranibizumab therapy has been accepted as a predominant treatment for CNV in recent years.

Inflammation in diabetic retinopathy: possible roles in pathogenesis and potential implications for therapy.

Diabetic retinopathy, characterized as a microangiopathy and neurodegenerative disease, is the leading cause of visual impairment in diabetic patients. Many clinical features observed in diabetic retinopathy, such as capillary occlusion, acellular capillaries and retinal non-perfusion, aggregate retinal ischemia and represent relatively late events in diabetic retinopathy. In fact, retinal microvascular injury is an early event in diabetic retinopathy involving multiple biochemical alterations, and is manifested by changes to the retinal neurovascular unit and its cellular components. Currently, intravitreal anti-vascular endothelial growth factor therapy is the first-line treatment for diabetic macular edema, and benefits the patient by decreasing the edema and improving visual acuity. However, a significant proportion of patients respond poorly to anti-vascular endothelial growth factor treatments, indicating that factors other than vascular endothelial growth factor are involved in the pathogenesis of diabetic macular edema. Accumulating evidence confirms that low-grade inflammation plays a critical role in the pathogenesis and development of diabetic retinopathy as multiple inflammatory factors, such as interleukin-1β, monocyte chemotactic protein-1 and tumor necrosis factor -α, are increased in the vitreous and retina of diabetic retinopathy patients. These inflammatory factors, together with growth factors such as vascular endothelial growth factor, contribute to blood-retinal barrier breakdown, vascular damage and neuroinflammation, as well as pathological angiogenesis in diabetic retinopathy, complicated by diabetic macular edema and proliferative diabetic retinopathy. In addition, retinal cell types including microglia, Müller glia, astrocytes, retinal pigment epithelial cells, and others are activated, to secrete inflammatory mediators, aggravating cell apoptosis and subsequent vascular leakage. New therapies, targeting these inflammatory molecules or related signaling pathways, have the potential to inhibit retinal inflammation and prevent diabetic retinopathy progression. Here, we review the relevant literature to date, summarize the inflammatory mechanisms underlying the pathogenesis of diabetic retinopathy, and propose inflammation-based treatments for diabetic retinopathy and diabetic macular edema.

Lost to follow-up of patients who received intravitreal anti-vascular endothelial growth factor therapy to treat four different retina disorders in an individual center in Brazil.

To identify risk factors for loss to follow-up in periodic intravitreal anti-vascular endothelial growth factor injections for the treatment patients with diabetic macular edema, subretinal neovascularization, age-related macular degeneration, and retinal vein occlusion in a single eye center in São Paulo, Brazil. This was a retrospective longitudinal study that gathered information from 992 patients who required intravitreal anti-vascular endothelial growth factor drugs over 6 months. The authors included age, eye disease, laterality, monthly income, distance, and payment mode as risk factors. Two hundred and seventy patients (29.93%) were lost to follow-up. Multivariate analysis showed age, monthly income, eye involvement, and type of medical assistance independently associated with loss to follow-up. The odds of loss to follow-up were greater among older patients than those less than 50 years (reference), p < 0.001. The odds of loss to follow-up were greater among patients who received unilateral treatment than those who received bilateral injections (p = 0.013). Concerning gross monthly income, there were no differences in the odds of the four salary strata; the data also indicate an absence of difference in the three strata of patients' distance to the clinic. Considering the diagnosis, only age-related macular degeneration showed greater odds of loss to follow-up (p = 0.016). Finally, the data suggest greater odds of loss to follow-up in private patients than in those on a health care plan (p < 0.001). Loss to follow-up is paramount because many patients may remain unassisted concerning their eye diseases. Identifying the risk factors is crucial to enforcing measures to increase adherence and the long-term success of the treatment.