Monthly Intravitreal Injections Research Articles

Intravitreal Injections of Bevacizumab (Avastin); which Dose is Recommended?

This study was conducted to evaluate the fast improvement, effectiveness & safety of intravitreal injections bevacizumab (Avastin), in different doses, for treating diabetic macular edema (DME). Eyes of 80 patients with diabetic macular edema were randomized and planned to receive three consecutive monthly intravitreal injections of 1.25 mg or 2.5 mg bevacizumab (forty patients for each group). Patients were observed for 4 weeks after 1st injection and the changes in the best-corrected visual acuity (BCVA), central macular thickness (CMT) and adverse events were compared between both groups. CMT was significantly reduced in both groups (P < 0.013). Significant improvements between baseline and 2weeks to 4weeks in the 2.5 mg group, were mean decrease in CMT was 318 t0 182(P<.001), mean BCVA is 0.16 improve to 0.7 and P value 0.001. Intraocular pressure (IOP)measurements post intravitreal (IV) bevacizumab injection was not raised its statistically significant (P < 0.001). CMT improvement with a dose of intravitreal IV injection 2.5 mg is promising a rapid safe effective response for treating DME without any ocular or systemic side effects but Follow-up is still short to make any specific treatment recommendations.

Short-term outcomes of intravitreal faricimab for refractory neovascular age-related macular degeneration.

To assess the short-term outcomes of intravitreal faricimab (IVF) for previously treated refractory neovascular age-related macular degeneration (nAMD) in a real-world setting. A retrospective monocentric study including 44 eyes treated with an upload of 4 × monthly intravitreal injections (IVI) of faricimab 6 mg/0.05 mL and followed for 4 weeks after last IVI (16 W). Patients were switched to IVF after treatment with at least three other anti-vascular endothelial growth factors (anti-VEGF). Main outcome measures included best-corrected visual acuity (BCVA), central macular thickness (CMT), subfoveal choroidal thickness (SFCT) and retinal fluid distribution. 44 eyes of 44 patients with previously treated refractory nAMD (63% males) were included. Mean age was 79 ± 7 years. The total number of previous anti-VEGF before switching to IVF was 32 ± 15 IVIs/eye. BCVA (logMAR) improved significantly from 0.65 ± 0.26 to 0.50 ± 0.23 at 16 W (p < 0.01). CMT (µm) decreased significantly from 422 ± 68 to 362 ± 47 at 16 W (p < 0.01). SFCT did not change significantly at 16 W (p = 0.06). The number of eyes with subretinal fluid (SRF) decreased significantly from 29 (65%) to 13 (29%) at 16 W (p = 0.001). There were no significant changes regarding the distribution of intraretinal fluid or pigment epithelial detachment (p > 0.05). A complete fluid resolution was achieved in 8 eyes (18%). No adverse events were noticed. In the short term, IVF led to a significant decrease in CMT as well as a significant improvement of BCVA and thus appears to be an effective treatment option for previously treated refractory nAMD without relevant adverse effects.

INCIDENCE AND CHARACTERISTICS OF NEOVASCULAR AGE-RELATED MACULAR WITH OVER A 12-MONTH REMISSION AFTER THREE MONTHLY AFLIBERCEPT ADMINISTRATION: 60 Months Results of a Pro Re Nata Regimen.

To investigate the characteristics of patients with over a 12-month remission after 3 monthly intravitreal aflibercept injections followed by a pro re nata regimen for exudative age-related macular degeneration (AMD). One hundred forty-four eyes with exudative AMD were included. All patients received 3 monthly intravitreal aflibercept injections as a loading dose, followed by an as-needed regimen for 60 months. Patients were classified into the remission and recurrence groups depending on the presence or absence of a 12-month remission. ARMS2 A69S and CFH I62V were genotyped in all cases. During the study, 82 eyes (56.9%) showed 12 months or more remission at least once. The cumulative incidence rate of a 12-month remission showed a plateau pattern and converged to 60% (y = -166.26x-2.172 + 0.6, R2 = 0.8168). Patients in the remission group were younger than those in the recurrence group (P < 0.001) and had less risk allele frequency of the ARMS2 gene than the recurrence group (P < 0.001). The longer the remission interval was prolonged, the better visual acuity was achieved at the 60-month visit (P < 0.001). Fifty-seven percent of patients showed a 12-month remission or more at least once during a 60-month follow-up, suggesting that patients with no reactivation can prolong the treatment interval.

Ranibizumab Port Delivery System in Neovascular Age-Related Macular Degeneration: Where Do We Stand? Overview of Pharmacokinetics, Clinical Results, and Future Directions.

The ranibizumab (RBZ) port delivery system (PDS) is a device designed to continuously deliver RBZ in the vitreous chamber for the treatment of neovascular age-related macular degeneration (nAMD). It is implanted during a surgical procedure and can provide sustained release of the medication for several months. This review, updated to January 2024, focuses on past clinical studies as well as current and forthcoming trials looking into a PDS with RBZ. In the phase 2 LADDER trial, the mean time to first refill of a PDS with RBZ 100 mg/mL was 15.8 months, with the pharmacokinetic (PK) profile showing a sustained concentration of RBZ in the blood and aqueous humor. More recently, a PDS with RBZ (100 mg/mL) refilled every 24 weeks was shown to be non-inferior to a monthly intravitreal injection (IVI) with RBZ (0.5 mg) over 40 and 92 weeks in the phase 3 ARCHWAY trial. The refill every 24 weeks allowed for a RBZ vitreous exposure within the concentration range of monthly intravitreal injections (IVIs), and the expected half-life (106 days) was comparable with the in vitro results. Nonetheless, vitreous hemorrhage and endophthalmitis were more common side effects in PDS patients. In conclusion, a PDS continuously delivering RBZ has a clinical effectiveness level comparable with IVI treatment. However, a greater frequency of unfavorable occurrences highlights the need for procedure optimization for a wider adoption. Ongoing trials and possible future approaches need to be addressed.

REDUCING TREATMENT BURDEN FOR AGE-RELATED MACULAR DEGENERATION PATIENTS: A SYSTEMATIC REVIEW OF RANIBIZUMAB PORT DELIVERY SYSTEM

Introduction and Objective: Ranibizumab port delivery system (PDS) is a newly developed method that provides a continuous, long-term supply of ranibizumab into the vitreous, reducing the burden of monthly intravitreal injection visits for neovascular age-related macular degeneration (nAMD) patients. This review aims to evaluate the efficacy and safety of ranibizumab PDS in nAMD. Methods: An extensive literature search was performed on 4 online databases: PubMed, Cochrane, ProQuest, and ScienceDirect. The inclusion criteria are human studies comparing ranibizumab port delivery system and intravitreal ranibizumab, English language, with full-text journal available. The main outcome measurements are best-corrected visual acuity (BCVA) in Early Treatment Diabetic Retinopathy Study (ETDRS) letters, central foveal thickness (CFT), and adverse events. Result: Two randomized controlled trials (RCTs) with a total of 635 adults were evaluated. At week 96, ranibizumab PDS reported observed mean BCVA changes from baseline (-1.0; +4.2; ETDRS letters) compared to monthly intravitreal ranibizumab (-1.1; +6.1; ETDRS letters). However, there was an increase in mean CFT changes from baseline (+9.9; -15.3 vs ?1.3; -21.3, µm) and more severe adverse events frequency (22; 4 vs 4; 0) with ranibizumab PDS versus monthly intravitreal ranibizumab, respectively. Conclusion: Ranibizumab PDS showed comparable visual outcomes to intravitreal ranibizumab while demonstrating marginally inferior anatomical outcomes and higher incidence of severe adverse effects. Despite this, with fewer treatment visits required for up to 24 weeks, ranibizumab PDS can potentially reduce the treatment burden in nAMD patients with poor compliance. Further studies are needed to provide better patient eligibility guidelines and recommendations for adverse event management of ranibizumab PDS.

Short-term response to anti-VEGF as indicator of visual prognosis in refractory age-related macular degeneration.

Some patients with neovascular age-related macular degeneration (nAMD) respond insufficiently to anti-VEGF treatment despite maximal monthly intravitreal injections. Their short-term response between injections was investigated for extent and visual prognosis. Monocentric retrospective observational study. 45 eyes from 41 patients with refractory nAMD (who previously received at least 12 months of anti-VEGF treatment), evaluated by optical coherence tomography (OCT) in between monthly anti-VEGF injections. The fluid profile on OCT was evaluated before, 1 week after, and 1 month after an intravitreal injection, using central retinal thickness (CRT), manual measurements, and fluid specific volumetric measurements performed by an automated algorithm based on artificial intelligence. A significant improvement was found at week 1 in terms of CRT (p < 0.0001), intraretinal (IRF) (p = 0.007), subretinal fluid (SRF) (p < 0.0001), and pigment epithelium detachment (PED) volume (p < 0.0001). Volumetric fluid measures revealed a >50% reduction at week 1 for both IRF and SRF for approximately two-thirds of eyes. Poorer short-term response was associated with larger exudative fluid amounts (IRF + SRF) (p = 0.003), larger PED (p = 0.007), lower visual acuity (p = 0.004) and less anatomic changes at treatment initiation (p < 0.0001). Univariate and multivariate analysis revealed that visual outcomes 4 and 5 years later was significantly worse with weaker short-term responsiveness (p = 0.005), with the presence of atrophy (p = 0.01) and larger PED volumes (p = 0.002). Incomplete responders to anti-VEGF showed a significant short-term response, identifiable at 1 week after injection, with rapid recurrence at 1 month. Weaker short-term responsiveness at 1 week was associated with poorer long term visual prognosis. These patients may need adjuvant treatment to improve their prognosis.

Clinical proof of concept for anti-FGF2 therapy in exudative age-related macular degeneration (nAMD): phase 2 trials in treatment-naïve and anti-VEGF pretreated patients

Background/ObjectiveIntravitreal injections of anti-vascular endothelial growth factor (VEGF) agents are the first-line treatment for exudative age-related macular degeneration (nAMD). Due to the limitations of these standard therapies, targeting alternative mechanisms of action may be helpful for treatment of this very common disease. Here, we investigated an anti-fibroblast growth factor-2 (FGF2) aptamer, umedaptanib pegol, a next generation therapeutic for the treatment of nAMD.MethodsThree phase 2 studies were designed. First, a multicentre, randomized, double-masked TOFU study assessed the efficacy of intravitreal injections of umedaptanib pegol monotherapy or in combination with aflibercept, compared to aflibercept monotherapy in 86 subjects with anti-VEGF pretreated nAMD. Second, 22 subjects who had exited the TOFU study received 4 monthly intravitreal injections of umedaptanib pegol (extension, RAMEN study). Third, as an investigator-sponsored trial (TEMPURA study), a single-center, open-label, 4-month study was designed to evaluate the safety and treatment efficacy of umedaptanib pegol in five naïve nAMD patients who had not received any prior anti-VEGF treatment.ResultsThe TOFU study demonstrated that umedaptanib pegol alone or in combination with aflibercept did not improve best-corrected visual acuity (BCVA) and central subfield thickness (CST) over aflibercept alone. However, the change in BCVA and CST at primary endpoint was marginal in all the three treatment groups, suggesting that umedaptanib pegol is effective to prevent the disease progression. The RAMEN study confirmed the cessation of disease progression. In the TEMPURA study, naïve nAMD patients showed improvement and no further macular degeneration, with striking improvement of visual acuity and central subfield thickness in some of the patients.ConclusionsThese results demonstrate, for the first time, clinical proof of concept for aptamer based anti-FGF2 therapy of nAMD.

Intravitreal fasudil monotherapy for treatment of refractory diabetic macular edema: A prospective interventional case series

Suboptimal response to conventional treatments in refractory diabetic macular edema (rDME) encourages efforts to identify new therapeutic options. To evaluate the effect of three monthly intravitreal injections of a Rho-associated protein kinase (ROCK) inhibitor (Fasudil, Asahi Kasei Pharma Corporation, Tokyo, Japan) in eyes with rDME. Ten eyes of 10 patients with DME unresponsive to at least six previous intravitreal bevacizumab (IVB) injections were recruited and underwent 3 consecutive monthly intravitreal injection of 0.025mg/0.05mL Fasudil. Best-corrected visual acuity (BCVA) and central macular thickness (CMT) were evaluated as functional and anatomical response indicators, respectively. The mean age was 60.1±5.1 years (range, 53-68). Five cases responded to treatment, two with both anatomical and functional responses (reduction of CMT from 521 to 395 and from 390 to 301 microns and improvement of BCVA from 0.3 to 0.1 LogMAR and 0.6 to 0.4 LogMAR, respectively) and three with only functional improvement (0.7 to 0.4; 0.7 to 0.4; and 0.3 to 0.1 LogMAR). Of note, cases with no significant change in CMT showed morphologic improvement of the retinal microstructure to some extent. No adverse event was observed during the study period. Monotherapy with intravitreal injection of ROCK inhibitors appears to have moderate visual benefits in eyes with DME refractory to IVB. Such effects may be functionally significant without obvious anatomical improvement.

Case Report: Optical coherence tomography angiography findings in radiation retinopathy

We report the observation of a 31-year-old patient followed for a nasopharyngeal carcinoma since 2009, treated by locoregional radiotherapy, with a cumulative dose of 70 Gray. This case presented all ocular complications of radiotherapy; radiation retinopathy (RR), which is the most severe complication, could be diagnosed earlier and have a better prognosis if optic coherence tomography angiography (OCTA) was performed. She presented with a progressive decline in bilateral visual acuity. Ophthalmologic examination revealed bilateral posterior subcapsular cataract, radiation retinopathy, and optic neuropathy. The OCT B-scan showed more pronounced macular edema in the right eye. The OCTA revealed enlargement of the central avascular zone and loss of the deep and superficial retinal vascular network. The patient received three consecutive monthly intravitreal injections of anti-vascular endothelial growth factor (VEGF), without improvement in visual acuity. The aim of this case report is to present the contribution of OCT-A in the diagnosis of radiation maculopathy, and attribute these changes to ischemia at the level of the retinal vascular network.

Three-month outcomes of faricimab loading therapy for wet age-related macular degeneration in Japan

This multicenter study aimed to assess the short-term effectiveness and safety of faricimab in treatment-naïve patients with wet age-related macular degeneration (wAMD) in Japan. We retrospectively reviewed 63 eyes of 61 patients with wAMD, including types 1, 2, and 3 macular neovascularization as well as polypoidal choroidal vasculopathy (PCV). Patients received three consecutive monthly intravitreal injections of faricimab as loading therapy. Over these 3 months, visual acuity improved gradually compared to baseline. Moreover, the central foveal thickness decreased significantly at 1, 2, and 3 months compared to baseline (p < 0.0001). At 3 months after initiation of faricimab therapy, a dry macula (defined as absence of intraretinal or subretinal fluid) was achieved in 82% of the eyes. Complete regression of polypoidal lesions was observed in 52% of eyes with PCV. Subfoveal choroidal thickness also decreased significantly at 1, 2, and 3 months compared to baseline (p < 0.0001). Although retinal pigment epithelium tears developed in two eyes, there were no other ocular or systemic complications observed during the 3 months of loading therapy. In conclusion, loading therapy using faricimab resulted in improved visual acuity and retinal morphology in Japanese patients with wAMD without particular safety issues.

Release of ranibizumab using a porous poly(dimethylsiloxane) capsule suppressed laser-induced choroidal neovascularization via the transscleral route

The administration of anti-vascular endothelial growth factor drugs in the posterior eye segment with sustained release through less invasive methods is a challenge in the treatment of age-related macular disease. We developed a flexible capsule device using porous poly(dimethylsiloxane) (PDMS) that was able to release ranibizumab. The porous PDMS sheet was fabricated by salt-leaching of a micro-sectioned PDMS sheet containing salt microparticles. Observation with scanning electron microscopy revealed that the pore densities could be adjusted by the concentration of salt. The in vitro release study showed that the release rate of fluorescein isothiocyanate-tagged albumin could be adjusted based on the pore density of the porous PDMS sheet. Ranibizumab could be released in a sustained-release manner for 16 weeks. The device was implanted on the sclera; its efficacy in terms of the suppression of laser-induced choroidal neovascularization (CNV) in rats was compared with that of monthly intravitreal injections of ranibizumab. At 8 and 18 weeks after implantation, the CNV area was significantly reduced in rats that received the ranibizumab-releasing device compared with those that received the placebo device. However, although monthly intravitreal injections of ranibizumab reduced CNV for 8 weeks, this reduction was not sustained for 18 weeks. In conclusion, we demonstrated a novel controlled-release device using a porous PDMS sheet that could suppress CNV via a less invasive transscleral route versus intravitreal injections. This device may also reduce the occurrence of side effects associated with frequent intravitreal injections.Graphical

Efficacy and safety of brolucizumab for serous drusenoid pigment epithelium detachment non-responder to bevacizumab and aflibercept.

We report the case of a woman with drusenoid pigment epithelial detachment (DPED) in age-related macular degeneration who was successfully treated with two monthly intravitreal injections of brolucizumab after failing to respond to previous intravitreal injections of bevacizumab and aflibercept. A 56-year-old woman with mixed DPED and overlying subretinal fluid in her right eye was initially treated with three intravitreal injections of bevacizumab and three intravitreal injections of aflibercept with no visual and anatomical improvement. Switching to intravitreal injection of brolucizumab was performed. After two consecutive monthly intravitreal injections of brolucizumab, optical coherence tomography (OCT) showed first subretinal fluid resolution and then DPED collapse in the following months. After nine months, the best corrected visual acuity had improved from 20/40 to 20/20. There were no signs of retinal atrophy and exudative activity on OCT examination. No serious or minor adverse events were reported during the follow-up period. Switching to intravitreal brolucizumab injection might be an effective therapeutic option for treatment of mixed DPED with subretinal fluid refractory to other anti-VEGF drugs.

Case Report: Optical coherence tomography angiography findings in radiation retinopathy

We report the observation of a 31-year-old patient followed for a nasopharyngeal carcinoma since 2009, treated by locoregional radiotherapy, with a cumulative dose of 70 Gray. This case presented all ocular complications of radiotherapy; radiation retinopathy (RR), which is the most severe complication, could be diagnosed earlier and have a better prognosis if optic coherence tomography angiography (OCTA) was performed. She presented with a progressive decline in bilateral visual acuity. Ophthalmologic examination revealed bilateral posterior subcapsular cataract, radiation retinopathy, and optic neuropathy. The OCT B-scan showed more pronounced macular edema in the right eye. The OCTA revealed enlargement of the central avascular zone and loss of the deep and superficial retinal vascular network. The patient received three consecutive monthly intravitreal injections of anti-vascular endothelial growth factor (VEGF), without improvement in visual acuity. The aim of this case report is to present the contribution of OCT-A in the diagnosis of radiation maculopathy, and attribute these changes to ischemia at the level of the retinal vascular network.

Dry Eye and Meibomian Gland Dysfunction in Neovascular Age-Related Macular Degeneration Patients Treated with Intravitreal Injections.

Objectives:To determine if patients treated with multiple intravitreal injections for neovascular age-related macular degeneration are more likely to suffer from dry eye and meibomian gland dysfunction.Materials and Methods:Sixty eyes of 30 patients were enrolled. One eye of each patient was treated with multiple monthly intravitreal injections for neovascular AMD (Group 1) and the fellow healthy eye received no treatment (Group 2). The presence of dry eye was evaluated using tear film break-up time, Schirmer 1 test, the Oxford scale, and Ocular Surface Disease Index (OSDI). The loss rate of meibomian glands was evaluated by meibography and was graded and scored (meiboscore) from grade 0 (no loss of glands) to grade 3 (loss of >2/3 of total meibomian glands) for each eyelid.Results:Group 1 had lower mean Schirmer 1 and tear film break up-time measurements and higher mean OSDI score than Group 2, but the differences were not statistically significant (p=0.257, p=0.113, and p=0.212, respectively). Mean Oxford scale scores and meiboscore of the upper eyelids showed no statistically significant difference between the groups (p=0.594, p=0.663, respectively). The meiboscore of the lower eyelids was significantly higher in Group 1 (p=0.048).Conclusion:Multiple factors such as povidone-iodine and the preservatives in topical eye drops may cause inflammation leading to ocular surface damage in patients treated with multiple intravitreal injections. As the treatment requires repeated injections, exposure to these factors might worsen the ocular surface inflammation. The possibility of dry eye and meibomian gland dysfunction should be considered in these patients.

A Randomized, Controlled Trial of Treat-and-Extend vs. Pro Re Nata Regimen for Neovascular Age-Related Macular Degeneration.

PurposeTo compare the efficacy and safety of conbercept using a treat-and-extend (T&E) regimen vs. a pro re nata (PRN) regimen in Chinese patients with neovascular age-related macular degeneration (nAMD).MethodsThis was a randomized, multicenter, non-inferiority study. After an initial loading phase of three consecutive monthly intravitreal injections of 0.5 mg Conbercept, the patients were treated to PRN or T&E regimen. The prespecified retreatment criteria was defined as a more than 5-letter decrease in BCVA from the previous visit or any evidence of new retinal hemorrhages, or the presence of any IRF and any SRF of more than 200 μm in height at the sub-foveal center. The primary outcome was the mean change in best-corrected visual acuity (BCVA) from baseline to 24 months, with a prespecified non-inferiority limit of −5 letters.ResultsFrom July 2016 through August 2018, 141 participants were allocated and treated (T&E, n = 69; PRN, n = 72). About one fifth of the overall participants were dropped out during the 12-month follow-up (28/141, 19.9%), and about one thirds of the overall participants were lost during the 24-month follow-up (51/141, 36%). At 2 years, mean BCVA letter improvement was + 4.0 in the T&E group vs. + 5.1 in the PRN group, and T&E regimen was not non-inferior to PRN regimen [difference, −1.169 letters; 95% confidence interval (CI): −6.864 ∼ 4.526]. Subgroup analyses also demonstrate the similar results in PCV patients, naive patients and no-naive patients. The mean decrease in central subfield thickness were 180 ± 165 μm in the T&E group and 247 ± 230 μm in the PRN group, respectively. The patients in the PRN group had required significantly fewer injections than those in the T&E group (12.4 vs. 14.6 injections, P = 0.041). The types and rates of adverse events were comparable in the two treatment groups.ConclusionThese findings suggest that the T&E regimen was not non-inferior to the PRN regimen in patients with nAMD in terms of BCVA outcomes through 24 months.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT02802657.

OCTA changes following loading phase with intravitreal aflibercept for DME

ObjectifMesurer les variations observées à l'angiographie-tomographie par cohérence optique (OCTA) à la suite de l'administration intravitréenne d'anti-VEGF (facteur de croissance endothélial vasculaire) dans le traitement de l’œdème maculaire diabétique (OMD), et évaluer le lien entre les paramètres mesurés à l'OCTA avant le traitement et les résultats visuels. NatureÉtude de cohorte prospective. MéthodesUn groupe de 29 patients présentant un OMD ont reçu 5 injections intravitréennes mensuelles d'aflibercept. On a eu recours au test de Wilcoxon pour observations appariées afin de comparer les données mesurées à l'OCTA au départ et après 6 mois. Au nombre des paramètres mesurés à l'OCTA, citons l'aire de la zone fovéale avasculaire (ZFA), le périmètre de la ZFA, la circularité de la ZFA, la densité vasculaire du plexus vasculaire superficiel (segmenté conformément à la cartographie de l’étude ETDRS [Early Treatment of Diabetic Retinopathy Study], soit zone centrale, zone interne, zone externe et zone complète). Une sous-analyse a permis de séparer les patients en 2 groupes : sujets qui ont répondu au traitement (réduction de l’épaisseur du sous-champ central > 50 µm pendant le traitement) et sujets qui n'ont pas répondu au traitement. Une régression linéaire multiple et une régression logistique ont servi à déterminer les liens entre les paramètres mesurés à l'OCTA avant le traitement et les résultats en matière d'acuité visuelle. RésultatsUn total de 29 patients ont été inclus: 25 patients (86,2 %) présentaient une rétinopathie diabétique non proliférante et 4 (13,8 %), une rétinopathie diabétique proliférante. La densité vasculaire a diminué dans les zones centrale (p = 0,004) et interne (p = 0,013) selon la cartographie de l’étude ETDRS. Cet effet n’était significatif que chez les patients qui ont répondu au traitement (zone centrale; p = 0,002; zone interne; p = 0,017). Les paramètres OCT et OCTA mesurés avant le traitement n'ont pas influé sur les résultats ultimes en matière d'acuité visuelle. ConclusionOn a noté, après l'administration intravitréenne d'aflibercept dans le traitement de l'OMD, une diminution significative de la densité vasculaire du plexus vasculaire superficiel dans les zones centrale et interne selon la cartographie de l'ETDRS. Ce phénomène s'est produit exclusivement chez les patients qui ont répondu au traitement. Nos observations tiennent vraisemblablement aux limites de la technologie de l'OCTA elle-même, en ce sens que la densité vasculaire avant le traitement a potentiellement été surestimée par la présence d'artéfacts, soit quelques particules en suspension en mouvement. Les paramètres mesurés à l'OCTA avant le traitement n'ont pas pu servir de biomarqueurs permettant de prévoir les résultats visuels après l'administration d'un anti-VEGF.

Prediction of the short-term efficacy of anti-VEGF therapy for neovascular age-related macular degeneration using optical coherence tomography angiography

BackgroundTo evaluate whether the specific choroidal neovascularization (CNV) characteristics measured using optical coherence tomography angiography (OCTA) can predict the 6-month prognosis of neovascular age-related macular degeneration (nAMD) after anti-vascular endothelial growth factor (anti-VEGF) therapy.MethodsPatients with type 1, type 2, or mixed-type neovascularization (NV) were prospectively included. Participants underwent an initial loading phase of three consecutive monthly intravitreal injections of Conbercept (0.5 mg) and were switched to a pro re nata (PRN) treatment strategy. OCTA images were evaluated for eyes that underwent follow-up assessments for more than 6 months. CNV lesions were manually segmented, and the CNV area, vessel area, greatest vascular caliber (GVC), and greatest linear dimension (GLD) were compared between responders and non-responders. Two masked graders independently measured the above-mentioned parameters using OCTA, and consistency was assessed using the intraclass correlation coefficient (ICC) values. Multiple logistic regression analysis was performed to evaluate the effect of a 3-month change in the CNV area, GLD, and GVC on the 6-month response to anti-VEGF agents.ResultsAmong the 60 eyes of 60 patients with nAMD, 39 were responders and 21 were non-responders. The proportion of CNV types was significantly different between responders and non-responders (P = 0.009). Patients with type 2 or mixed NV seemed more likely to respond to the treatment (28.2% vs. 0.0%, and 30.8% vs. 23.8%, respectively). The change in GVC showed a significant difference between responders (− 4.98 ± 17.17 μm) and non-responders (11.01 ± 14.10 μm) after three monthly intravitreal anti-VEGF injections. Multiple logistic regression analysis showed that only the change in GVC remained significant after controlling for baseline GVC, injection number, and CNV type (adjusted OR = 1.083; P = 0.008).ConclusionsType 2 and mixed-type NV were significantly associated with a better response to anti-VEGF therapy. Changes in GVC after 3 months of treatment were significantly associated with a response to anti-VEGF therapy at 6 months.

Acute Syphilitic Posterior Placoid Chorioretinitis With Subfoveal Choroidal Neovascularization Managed With Anti-VEGF Therapy.

We describe the development and management of choroidal neovascularization (CNV) in a patient with acute syphilitic posterior placoid chorioretinitis (ASPPC). A retrospective case review is presented. A 66-year-old man presented with unilateral blurry vision. He had a history of systemic syphilis infection twice, the last diagnosed 15 years before presentation and treated with intravenous ceftriaxone, resulting in seroreversion of an initially positive rapid plasma reagin (RPR). Examination revealed ASPPC with subfoveal CNV. Repeat testing revealed an RPR titer of 1:16 384. He was treated with 6 monthly intravitreal injections of bevacizumab and systemic antibiotics, resulting in resolution of his ASPPC and regression of his CNV. CNV is a rare complication of ASPPC. Multimodal imaging can be useful to suggest the diagnosis, and prompt treatment with systemic antibiotics and intravitreal anti-vascular endothelial growth factor agents can lead to resolution of ASPPC and regression of CNV, respectively.

Aortic stiffness and systemic inflammation changes predict clinical response to intravitreal anti-vascular endothelial growth factor therapy in patients with age-related macular degeneration.

Aortic stiffness and systemic inflammation are predictors of cardiovascular risk. Anti-vascular endothelial growth factor agents (anti-VEGF), injected intravitreally, can reverse the course of exudate age-related macular degeneration (AMD). We sought to investigate the association of changes in aortic stiffness and systemic inflammation with response to anti-VEGF therapy. 54 patients (mean age: 76 ± 10 years) with AMD received two consecutive monthly intravitreal injections of ranibizumab (0.5 mg). The primary outcome measure was change in carotid-femoral pulse wave velocity (PWV) from baseline to 1 month after the second injection. Secondary endpoint was the change in serum high sensitivity interleukin-6 (hsIL-6) levels. Ranibizumab caused a decrease of PWV after the first (by 0.36 ± 1.4 m/s) and the second injection (by 0.31 ± 1.4 m/s) and remained decreased 1 month after the second injection (overall P < 0.05). PWV decreased significantly in good responders (according to clinical criteria and fundus findings, P = 0.004), whereas it increased numerically in poor responders (P = 0.21) over the study period. In responders, hsIL-6 decreased after the first injection and remained decreased 1 month after the second injection (by 0.63 ± 0.35 pg/ml, overall P = 0.02). PWV (P = 0.005) and hsIL-6 (P = 0.042) were independent predictors of improvement after adjusting for age and presence of hypertension and diabetes. The decrease in PWV through the whole study period was positively correlated with the reduction in hsIL-6 (r = 0.36, P < 0.01). Intravitreal ranibizumab injections lead to a decrease in PWV and hsIL-6. Both parameters predict clinical improvement and may aid to improving treatment targeting and hence therapeutic outcome in patients with AMD.

SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY BIOMARKERS OF RETINAL HYPERPERMEABILITY AND CHOROIDAL INFLAMMATION AS PREDICTORS OF SHORT-TERM FUNCTIONAL AND ANATOMICAL OUTCOMES IN EYES WITH DIABETIC MACULAR EDEMA TREATED WITH INTRAVITREAL BEVACIZUMAB

Purpose: To assess spectral domain optical coherence tomography biomarkers of short-term outcomes in eyes with diabetic macular edema treated with intravitreal bevacizumab. Methods: In a prospective interventional case series, 66 eyes with diabetic macular edema underwent 3 monthly intravitreal bevacizumab injections. Best-corrected visual acuity measurement and spectral domain optical coherence tomography were performed at baseline and at 3 months. Multivariate regression analysis was performed to investigate the baseline spectral domain optical coherence tomography parameters as predictors of functional and anatomical outcomes. Results: Patients with diabetic nephropathy had greater subfoveal choroidal thickness (300.8 ± 35.54 vs. 253.0 ± 50.07 µm, P &lt; 0.01) and were more likely to have subretinal fluid (r = 0.26, P = 0.03) at baseline. Multivariate analysis showed that the extent of external limiting membrane disruption (P = 0.03) and the extent of disorganization of retinal inner layers (P = 0.03) at baseline were predictors of best-corrected visual acuity at 3 months, whereas the extent of disorganization of retinal inner layers (P = 0.04) and duration of diabetes mellitus (P = 0.03) were predictors of central subfield thickness at 3 months. Conclusion: External limiting membrane disruption and disorganization of retinal inner layers, as the spectral domain optical coherence tomography biomarkers of retinal hyperpermeability, can predict short-term outcomes in diabetic macular edema eyes treated with intravitreal bevacizumab.