Subfoveal Choroidal Neovascularization Research Articles

Comparison of visual acuity outcome and choroidal thickness variation of intravitreal ranibizumab injection for myopic choroidal neovascularization with or without dome-shaped macula

BackgroundTo investigate the visual acuity outcome and choroid thickness (CT) change after intravitreal ranibizumab in highly myopic eyes with or without dome-shaped macula (DSM) in Chinese patients. MethodsThis retrospective, observative study included 80 treatment-naive eyes (80 patients), which received ranibizumab according to the 1+PRN protocol. The best corrective visual acuity (BCVA) and CT change were compared between eyes with or without DSM. ResultsThere was no significant difference between eyes with or without DSM in BCVA and central macular thickness (CMT). The recurrent rate was not different between the two groups during the first year of treatment. The CT was significantly thinner in eyes with DSM than in eyes without DSM before treatment (median 40.00um versus 71.00um), at 1 month after treatment (median 31.00um versus 65.50um), and in the last follow up (median, 32.00um versus 65.00um) (p = 0.0101). Axial length (AL) was longer in eyes with DSM than those without DSM (median, 29.17 mm versus 28.10 mm) before treatment, and in the last follow up (median, 29.44 mm versus 28.20 mm) (p = 0.0055). The CT was significantly correlated with AL (p < 0.0001). ConclusionsNo difference was found in visual outcome between eyes with or without DSM. The visual acuity significantly improved at 1 month after ranibizumab injection and it was recovery sooner in extrafoveal choroidal neovascularization (CNV) group than in subfoveal CNV group. The CT was thinner in eyes with DSM, which was significantly correlated with AL.

Comparison of the efficacy and safety of SCD411 and reference aflibercept in patients with neovascular age-related macular degeneration

To compare the efficacy and safety of the proposed aflibercept biosimilar SCD411 and reference aflibercept in patients with neovascular age-related macular degeneration, this randomized, double-masked, parallel-group, multicenter study was conducted in 14 countries from 13 August 2020 to 8 September 2022. Patients with neovascular age-related macular degeneration. With subfoveal, juxtafoveal, or extrafoveal choroidal neovascularization were aged 50 years or older. Intravitreal injection of SCD411 or aflibercept (2.0 mg) were administered every 4 weeks for the first three injections and every 8 weeks until week 48. The primary efficacy endpoint was the change in best-corrected visual acuity from baseline to week 8 with an adjusted equivalence margin of ± 3.0 letters. Patients were randomly assigned to receive either SCD411 (n = 288) or reference aflibercept (n = 288). A total of 566 participants (98.3%) completed week 8 of the study. The least-squares mean difference of change in best-corrected visual acuity from baseline to week 8 (SCD411—aflibercept) was − 0.4 letters (90% confidence interval = − 1.6 to 0.9). The incidence of ocular (69 of 287 [24.0%] vs. 71 of 286 [24.8%]) and serious ocular (5 of 287 [1.7%] vs. 3 of 286 [1.0%]) treatment-emergent adverse effects were similar between the SCD411 and aflibercept groups. Immunogenicity analysis revealed a low incidence of neutralizing antibody formation in both groups. In conclusion, SCD411 has equivalent efficacy compared with reference aflibercept in patients with neovascular age-related macular degeneration and has a comparable safety profile. The results support the potential use of SCD411 for the treatment of neovascular age-related macular degeneration.

Evaluating the Efficacy and Safety of Aflibercept Biosimilar (P041) Compared with Originator Product in Patients with Neovascular Age-Related Macular Degeneration

ObjectiveTo assess the non-inferiority of biosimilar aflibercept (CinnaGen Company, Iran) (P041) to the originator aflibercept (Regeneron, US) (AFL) in terms of efficacy, safety, and immunogenicity. DesignThis was a phase Ш, 52-week, multicenter, randomized, double-masked, and active control trial involving eyes in a 1:1 ratio. SubjectsPatients with active subfoveal choroidal neovascularization secondary to age-related macular degeneration randomized into the two groups of P041 and AFL. Methods and InterventionsPatients received an injection of aflibercept every 4 weeks for 3 doses, followed by administration every 8 weeks up to week 48. Main Outcome MeasuresThe primary outcome was the non-inferiority analysis of eyes maintaining vision at week 52. Secondary outcomes included the changes in visual acuity (VA) and retinal thickness, safety evaluation, and immunogenicity during the study. ResultsIn total, 168 eyes of 168 patients were included. At week 52, the proportion of patients maintaining vision was 94.44% in P041 compared to 94.52% in AFL group. The 95% confidence interval (CI) for the difference of maintaining vision from baseline did not exceed the predefined non-inferiority margin of 10% (p-value: 0.98, 95% CI, -0.0008 (-0.074, 0.074)). Secondary outcomes indicated similar results in both arms (all p-values >0.05). Safety measured outcomes and immunogenicity were similar between the two study groups. ConclusionP041 was noninferior to AFL in eyes with n-AMD. Other efficacy and safety findings also indicated the similarity of two products.

Efficacy and Safety of Biosimilar QL1207 vs. the Reference Aflibercept for Patients with Neovascular Age-Related Macular Degeneration: A Randomized Phase 3 Trial.

This trial aimed to compare the efficacy and safety between biosimilar QL1207 and the reference aflibercept for the treatment of neovascular age-related macular degeneration (nAMD). This randomized, double-blind, phase 3 trial was conducted at 35 centers in China. Patients aged ≥ 50years old with untreated subfoveal choroidal neovascularization secondary to nAMD and best-corrected visual acuity (BCVA) letter score of 73-34 were eligible. Patients were randomly assigned to receive intravitreous injections of QL1207 or aflibercept 2mg (0.05ml) in the study eye every 4weeks for the first 3months, followed by 2mg every 8weeks until week 48, stratified by baseline BCVA ≥ or < 45 letters. The primary endpoint was BCVA change from baseline at week 12. The equivalence margin was ± 5 letters. The safety, immunogenicity, pharmacokinetics (PK), and plasma vascular endothelial growth factor (VEGF) concentration were also evaluated. A total of 366 patients were enrolled (QL1207 group, n = 185; aflibercept group, n = 181) from Aug 2019 to Jan 2022 with comparable baseline characteristics. The least-squares mean difference in BCVA changeswas - 1.1 letters(95% confidence interval - 3.0 to 0.7; P = 0.2275) between the two groups, within the equivalence margin. The incidences of treatment-emergent adverse events (TEAE; QL1207: 71.4% [132/185] vs. aflibercept: 71.8% [130/181]) and serious TEAE (QL1207: 14.1% [26] vs. aflibercept: 12.7% [23]) appeared comparable between treatment groups, and no new safety signal was found. Anti-drug antibody, PK profiles, and VEGF concentration were similar between the two groups. QL1207 has equivalent efficacy to aflibercept for nAMD with similar safety profiles. It could be used as an alternative anti-VEGF agent for clinical practice. ClinicalTrials.gov: NCT05345236 (retrospectively registered on April 25, 2022); National Medical Products Administration of China: CTR20190937 (May 20, 2019).

Effect of High-Dose Intravitreal Aflibercept, 8 mg, in Patients With Neovascular Age-Related Macular Degeneration

Aflibercept, 8 mg, may have greater therapeutic benefits compared with aflibercept, 2 mg, in patients with neovascular age-related macular degeneration (nAMD), including potentially improved outcomes and decreased treatment burden. To assess safety and efficacy of aflibercept, 8 mg, in patients with nAMD. The CANDELA trial was a phase 2, randomized, single-masked, open-label, 44-week clinical trial conducted in the US. Treatment-naive patients with active subfoveal choroidal neovascularization secondary to nAMD and a best-corrected visual acuity score of 78 to 24 letters (approximately 20/32 to 20/320) in the study eye were enrolled between November 2019 and November 2021. Eligible participants were randomized 1:1 to receive 3 monthly doses of 8 mg (70 μL) or 2 mg (50 μL) of aflibercept followed by doses at weeks 20 and 32. Coprimary end points were the proportion of eyes without fluid (absence of intraretinal and subretinal fluid) in the central subfield at week 16 and safety. All 106 eligible eyes were randomized to receive aflibercept, 8 mg (n = 53), or aflibercept, 2 mg (n = 53). Overall, 66 participants (62.3%) were female. The proportion of eyes without fluid in the central subfield with 8-mg vs 2-mg aflibercept was 50.9% (n = 27) vs 34.0% (n = 18) (difference, 17.0 [95% CI, -1.6 to 35.5] percentage points; P = .08) at week 16 and 39.6% (n = 21) vs 28.3% (n = 15) (difference, 11.3 [95% CI, -6.6 to 29.2] percentage points; nominal P = .22) at week 44. At week 44, mean (SE) change in central retinal thickness was -159.4 (16.4) vs -137.2 (22.8) μm with 8 mg vs 2 mg of aflibercept, respectively (least squares mean difference, -9.5 [95% CI, -51.4 to 32.4]; nominal P = .65) and mean (SE) change in best-corrected visual acuity score was +7.9 (1.5) vs +5.1 (1.5) letters (least squares mean difference, +2.8 [95% CI, -1.4 to +7.0]; nominal P = .20). No differences in safety profiles between the groups were observed. Although aflibercept, 8 mg, did not achieve the primary efficacy end point at week 16 at the 2-sided significance level of 5%, the observed trends in anatomic and visual improvements over 44 weeks with aflibercept, 8 mg, indicate potential additional therapeutic benefit over aflibercept, 2 mg. No new safety signals were observed over 44 weeks. These findings support further evaluation of aflibercept, 8 mg, in pivotal trials of exudative retinal diseases including nAMD and diabetic macular edema. ClinicalTrials.gov Identifier: NCT04126317.

Machine Learning to Predict Response to Ranibizumab in Neovascular Age-Related Macular Degeneration

Neovascular age-related macular degeneration (nAMD) shows variable treatment response to intravitreal anti-VEGF. This analysis compared the potential of different artificial intelligence (AI)-based machine learning models using OCT and clinical variables to accurately predict at baseline the best-corrected visual acuity (BCVA) at 9 months in response to ranibizumab in patients with nAMD. Retrospective analysis. Baseline and imaging data from patients with subfoveal choroidal neovascularization secondary to age-related macular dengeration. Baseline data from 502 study eyes from the HARBOR (NCT00891735) prospective clinical trial (monthly ranibizumab 0.5 and 2.0 mg arms) were pooled; 432 baseline OCT volume scans were included in the analysis. Seven models, based on baseline quantitative OCT features (Least absolute shrinkage and selection operator [Lasso] OCT minimum [min], Lasso OCT 1 standard error [SE]); on quantitative OCT features and clinical variables at baseline (Lasso min, Lasso 1SE, CatBoost, RF [random forest]); or on baseline OCT images only (deep learning [DL] model), were systematically compared with a benchmark linear model of baseline age and BCVA. Quantitative OCT features were derived by a DL segmentation model on the volume images, including retinal layer volumes and thicknesses, and retinal fluid biomarkers, including statistics on fluid volume and distribution. Prognostic ability of the models was evaluated using coefficient of determination (R2) and median absolute error (MAE; letters). In the first cross-validation split, mean R2 (MAE) of the Lasso min, Lasso 1SE, CatBoost, and RF models was 0.46 (7.87), 0.42 (8.43), 0.45 (7.75), and 0.43 (7.60), respectively. These models ranked higher than or similar to the benchmark model (mean R2, 0.41; mean MAE, 8.20 letters) and better than OCT-only models (mean R2: Lasso OCT min, 0.20; Lasso OCT 1SE, 0.16; DL, 0.34). The Lasso min model was selected for detailed analysis; mean R2 (MAE) of the Lasso min and benchmark models for 1000 repeated cross-validation splits were 0.46 (7.7) and 0.42 (8.0), respectively. Machine learning models based on AI-segmented OCT features and clinical variables at baseline may predict future response to ranibizumab treatment in patients with nAMD. However, further developments will be needed to realize the clinical utility of such AI-based tools. Proprietary or commercial disclosure may be found after the references.

Focal laser and intravitreal bevacizumab for choroidal neovascularization secondary to Grönblad–Strandberg syndrome

Introduction: Pseudoxanthoma elasticum is a rare genetic disorder. It has several ocular features including angioid streaks and choroidal neovascularization which can significantly affect vision. Case Report: A 50-year-old man presented with nine months history of poor vision affecting both distant and near vision. His best corrected visual acuities were 6/18 right eye and 1/60 left eye. His anterior segments were normal. Funduscopy revealed linear hyperpigmented irregular branching peripapillary lesions; angioid streaks both eyes. He had bilateral speckled retina pigment epithelial hyperpigmented lesions interspaced with dot hemorrhages in the macula region suggestive of likely choroidal neovascularization. He had “peau d’orange” skin appearance around his neck. Fundus fluorescein angiography showed features of occult subfoveal choroidal neovascularization. He was referred to a physician and had a skin biopsy which revealed histologic features of Pseudoxanthoma elasticum. He was treated with bilateral focal argon laser. However he had right intravitreal Bevacizumab after a large ipsilateral subfoveal hemorrhage. His visual acuities remained stable afterward. Conclusion: Patients with Pseudoxanthoma elasticum have to be closely monitored for ocular manifestations. Choroidal neovascularization should be detected early and promptly treated. Antivascular endothelial growth factor injections have become the preferred treatment option for choroidal neovascularization in these patients.

Comparison of the outcome of limited protocol Ranibizumab injection in naïve choroidal neovascular membranes secondary to pathological myopia versus age-related macular degeneration

Aim We aimed to compare the anatomical and visual response of newly diagnosed choroidal neovascularization (CNV) secondary to pathological myopia or age-related macular degeneration with relatively poor initial vision to treatment with three intravitreal injections of ranibizumab. Patients and methods This prospective, comparative study included 29 eyes of 29 patients newly diagnosed with subfoveal active CNV, either secondary to age-related macular degeneration (AMD-CNV, 15 eyes) or to pathological myopia, that is, myopic CNV (MCNV, 14 eyes). All patients had an initial best-corrected visual acuity (BCVA) equal to or worse than 1.00 Log Mar. Patients received three intravitreal injections of 0.50 mg ranibizumab on a monthly basis. Patients were evaluated before injections and one month after each injection for BCVA and optical coherence tomography-measured retinal parameters: central macular thickness, total volume, and average thickness (AT). Amsler's chart was used to detect scotomas and metamorphopsias. Results One month after the three injections, a significant improvement was noted in the two groups in central macular thickness, total volume, and AT. The improvement was significantly better in AT of the AMD group. The mean BCVA improved significantly in the AMD group only as patients either improved or remained stationary, whereas in the MCNV group, 21% of patients deteriorated, which affected the significance of the overall mean of improvement (P=0.7823); the difference in the overall mean was insignificant. Despite that, almost half of the patients in each group had their visual acuity improved by an average of 9.5 letters in AMD and 10.7 in MCNV. Conclusion Naïve AMD-CNV and MCNV of initially poor VA can get significant improvement in all optical coherence tomography-measured retinal parameters following a three-injection course of ranibizumab on a monthly basis. VA improvement is more predictable in AMD, as no patients deteriorated after the injections, yet the overall difference in VA improvement between groups was insignificant.

Outer nuclear layer recovery as a predictor of visual prognosis in type 1 choroidal neovascularization of neovascular age-related macular degeneration

To investigate the changes in outer nuclear layer (ONL) thickness during anti-vascular endothelial growth factor (VEGF) treatment in type 1 choroidal neovascularization (CNV) and its impact on vision. Type 1 CNV eyes (n = 94) were retrospectively compared to normal control eyes (n = 35). Along with best-corrected visual acuity (BCVA), the location of CNV, foveal ONL thickness, and subretinal fluid height were measured using optical coherence tomography (OCT) and analyzed. Visual outcome and OCT biomarkers were compared. As a result, the CNV group had thinner foveal ONL and worse BCVA compared to the control group. ONL thickness recovered partially along with visual improvement following 3 monthly initial loading doses of aflibercept injections, and it correlated with the final BCVA during the 1-year follow-up. Eyes achieved foveal ONL recovery over + 10 µm had lower subfoveal CNV (45.5%) and showed better visual outcomes than eyes with stationary ONL or suboptimal ONL recovery (76.0%, p = 0.012). In conclusion, type 1 CNV eyes that recovered foveal ONL thickness at initial loading of anti-VEGF demonstrated good final visual outcome during the 1-year follow-up. Monitoring the foveal ONL thickness during early anti-VEGF treatment can give information about the visual outcomes in type 1 CNV.

Immunogenicity With Ranibizumab Biosimilar SB11 (Byooviz) and Reference Product Lucentis and Association With Efficacy, Safety, and Pharmacokinetics

SB11 and reference ranibizumab (RBZ) are monoclonal anti-vascular endothelial growth factor (VEGF)-A antibodies approved for the treatment of neovascular age-related macular degeneration (nAMD) and other retinal diseases. The association of ranibizumab immunogenicity and treatment outcomes in patients with nAMD is unclear but relevant regarding concerns about immunogenicity of anti-VEGF biological products. To examine the association of immunogenicity to ranibizumab products (SB11 and RBZ) with efficacy, safety, and pharmacokinetics. This was a post hoc analysis of a randomized, double-masked, parallel-group phase 3 equivalence study with participants from 75 centers in 9 countries conducted from March 14, 2018, to December 9, 2019. Included were participants 50 years or older with nAMD and active subfoveal choroidal neovascularization lesions. Intravitreal injection of SB11 or RBZ, 0.5 mg, every 4 weeks through week 48. Serum antidrug antibodies (ADAs) were analyzed during the study period until week 52 to measure immunogenicity. Analyses were performed on immunogenicity (overall ADA positivity) with best-corrected visual acuity (BCVA) and central subfield thickness (CST). Adverse events associated with intraocular inflammation (IOI) and serum ranibizumab levels were compared between overall ADA-positive and ADA-negative participants. A total of 705 participants (mean [SD] age, 74.1 [8.5] years; 403 female individuals [57.2%]) were included in the study. The overall incidence of ADA-positivity was 32 of 657 (4.9%) at week 52. The least-squares mean (SE) differences between overall ADA-positive and ADA-negative participants up to week 52 for BCVA and CST, respectively, were 1.6 (2.2) letters (95% CI, -2.7 to 5.8; P = .46) and 3 (13) μm (95% CI, -23 to 29; P = .83). IOI-related events occurred in 1 of 32 overall ADA-positive participants (3.1%) and 4 of 620 overall ADA-negative participants (0.6%). Mean (SD) serum ranibizumab concentrations over time were slightly lower in overall ADA-positive participants compared with those of ADA-negative participants, with a maximum value of 1389.3 (875.4) pg/mL at week 16 vs 1665.4 (1124.0) pg/mL at week 36, respectively. Results of this post hoc analysis of an equivalence trial suggest that immunogenicity was not associated with efficacy and safety of SB11 and RBZ in participants with nAMD. With a low overall ADA incidence, no clear association was identified between overall ADA positivity and pharmacokinetics. These findings support the biosimilarity of SB11 and RBZ, with no safety concern identified for SB11 vs RBZ associated with immunogenicity. ClinicalTrials.gov Identifier: NCT03150589.

Subretinal Fluid Resolution and Visual Acuity in Patients with Neovascular Age-Related Macular Degeneration: A HARBOR Post Hoc Analysis

To determine the effect of subretinal fluid (SRF) resolution on visual acuity in patients with neovascular age-related macular degeneration (nAMD) from the HARBOR trial. Post hoc analysis of the HARBOR trial (a phase 3, double-masked, randomized, active treatment-controlled trial of ranibizumab conducted between July 2009 and August 2012 [NCT00891735]) was carried out from January 2020 to July2021. Treatment-naive patients with nAMD and active subfoveal choroidal neovascularization (N= 1097). Multiple intervention arms were pooled for this analysis if SRF was present at baseline and intraretinal fluid/SRF resolved during the study, based on spectral-domain OCT (n= 349). Three monthly loading doses followed by intravitreal injections of 0.5-mg or 2.0-mg ranibizumab were administered monthly or pro re nata over 24 months. Mean change in ETDRS best-corrected visual acuity (BCVA) between the month before SRF resolution and the month of SRF resolution detection. Visual outcomes at months 12 and 24 were analyzed in eyes without SRF recurrence after SRF resolution. The proportion of patients who lost ≤ 4 letters were considered as vision gainers/maintainers and those who lost ≥ 5 were considered as vision losers. Of 349 patients, 32 patients (9%) lost ≥ 5 ETDRS letters (mean [95% confidence interval (CI)], -9.9 letters [-12.0,-7.9]) and 317 (91%) of the eyes gained/maintained BCVA (mean, 6.1 letters [95% CI, 5.3, 6.8]) between the month before SRF resolution and the month of SRF resolution. There were no differences in baseline ocular characteristics between patient groups. Among eyes without SRF recurrence after SRF resolution (64%; 224/349), eyes that lost ≥ 5 ETDRS letters compared with those that gained/maintained letters at the time of SRF resolution had reduced visual outcome gains from baseline to month 12 (1.4 vs. 12.9 letters) and month 24 (0.0 vs. 12.6 letters). A greater proportion of ranibizumab-treated eyes with nAMD gained/maintained visual acuity at SRF resolution. Approximately 9% of eyes lost vision during SRF resolution; these eyes had reduced final visual acuity gains at 12 and 24 months. Further analyses are warranted to investigate potential underlying factors and discuss the treatment implications if confirmed.

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.

Spontaneous regression and quiescence of choroidal neovascularization secondary to traumatic choroidal rupture depicted on OCT angiography.

Choroidal rupture is a tear/break within the Bruch's membrane, retinal pigment epithelium and choroid following blunt trauma. Choroidal neovascularization is a well-known complication of traumatic choroidal rupture that is typically treated with intravitreal injections of Bevacizumab. This case describes an early detection of choroidal neovascular complex secondary to traumatic choroidal rupture and its spontaneous regression and quiescence without treatment followed using optical coherence tomography (OCT) angiography. A healthy 19 year old female presented with decreased vision in her left eye following a blunt non-penetrating closed globe injury two weeks prior. A complete ophthalmic examination with ancillary testing was consistent with sub-foveal choroidal neovascularization secondary to traumatic choroidal rupture. Five weeks later, there was spontaneous regression of the choroidal neovascular complex as depicted on OCT angiography and complete resolution of subretinal fluid/exudation on structural OCT. A conservative approach without intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections was chosen for management. To the authors' knowledge this is a first case describing a unique evolution with spontaneous regression and quiescence of choroidal neovascularization secondary to traumatic choroidal rupture without treatment followed using OCT angiography. Expectant management may be a viable treatment option for this condition.

Sustained-Release Microspheres of Rivoceranib for the Treatment of Subfoveal Choroidal Neovascularization.

The wet type of age-related macular degeneration (AMD) accompanies the subfoveal choroidal neovascularization (CNV) caused by the abnormal extension or remodeling of blood vessels to the macula and retinal pigment epithelium (RPE). Vascular endothelial growth factor (VEGF) is known to play a crucial role in the pathogenesis of the disease. In this study, we tried to repurpose an investigational anticancer drug, rivoceranib, which is a selective inhibitor of VEGF receptor-2 (VEGFR2), and evaluate the therapeutic potential of the drug for the treatment of wet-type AMD in a laser-induced CNV mouse model using microsphere-based sustained drug release formulations. The PLGA-based rivoceranib microsphere can carry out a sustained delivery of rivoceranib for 50 days. When administered intravitreally, the sustained microsphere formulation of rivoceranib effectively inhibited the formation of subfoveal neovascular lesions in mice.

Choroidal neovascularization in 111 eyes of children and adolescents.

To describe the clinical features, management, and outcomes of choroidal neovascularization (CNV) in children less than 18years of age. This was a retrospective, case control study of 111 eyes of 96 patients. CNV was clinically diagnosed in all patients. Eyes were classified as those that were observed (Controls; Group 1) or those that had treatment (Cases; Group 2). CNV was categorized as regressed, persistent, or recurrent in order to evaluate the anatomical outcomes. Of 96 patients, 68(71%) were male. Mean presenting age was 11.4 ± 3.4years (median = 11years, range = 1-17years). CNV was bilateral in 15(16%) patients. Of 111 eyes, 38 eyes had treatment (Cases) and 73 eyes did not (Natural history group or Controls). Subfoveal CNV was seen in majority of cases (59%). Most common etiology was post-inflammatory (38%), followed by trauma (16%). Eyes were classified as those that were observed (controls; Group 1) or those that had treatment (cases; Group 2). In group 1, spontaneous regression of CNV was seen in 26(36%) eyes and there was no recurrence in this group. In group 2 following treatment, 25(66%) of 38 eyes achieved complete regression at mean 4.9months and was persistent in 5 eyes. CNV recurrence was seen in 10 eyes with the mean time to first recurrence being 9months. At presentation, mean best-corrected visual acuity (BCVA) of eyes with subfoveal CNV was logMAR 0.99 that improved to logMAR 0.63 with treatment. Mean follow-up was 17months. CNV results in significant visual decline in children; most commonly of post-inflammatory etiology. Treatment achieves high regression rates, albeit with limited visual improvement.

Efficacy and Safety of Biosimilar FYB201 Compared with Ranibizumab in Neovascular Age-Related Macular Degeneration

This trial was conducted to investigate the clinical equivalence of the proposed biosimilar FYB201 and reference ranibizumab in patients with treatment-naive, subfoveal choroidal neovascularization caused by neovascular age-related macular degeneration (nAMD). This was a prospective, multicenter, evaluation-masked, parallel-group, 48-week, phase III randomized study. A total of 477 patients were randomly assigned to receive FYB201 (n= 238) or reference ranibizumab (n= 239). Patients received FYB201 or reference ranibizumab 0.5 mg by intravitreal (IVT) injection in the study eye every 4 weeks. The primary end point was change from baseline in best-corrected visual acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) letters at 8 weeks before the third monthly IVT injection. Biosimilarity of FYB201 to its originator was assessed via a 2-sided equivalence test, with an equivalence margin in BCVA of 3 ETDRS letters. The BCVA improved in both groups, with a mean improvement of+5.1 (FYB201) and+5.6 (reference ranibizumab) ETDRS letters at week 8. The analysis of covariance (ANCOVA) least squares mean difference for the change from baseline between FYB201 and reference ranibizumab was -0.4 ETDRS letters with a 90% confidence interval (CI) of -1.6 to 0.9. Primary end point was met as the 90% CI was within the predefined equivalence margin. Adverse events were comparable between treatment groups. FYB201 is biosimilar to reference ranibizumab in terms of clinical efficacy and ocular and systemic safety in the treatment of patients with nAMD.

Autosomal Recessive Bestrophinopathy: Clinical and Genetic Characteristics of Twenty-Four Cases.

Background To describe ocular manifestations, imaging characteristics, and genetic test results of autosomal recessive bestrophinopathy (ARB). The study design is an observational case series. Methods Forty-eight eyes of 24 patients diagnosed with ARB underwent complete ophthalmic examinations including refraction, anterior and posterior segment examination, enhanced depth imaging optical coherence tomography (EDI-OCT), fluorescein angiography (FA), electroretinography (ERG), and electrooculography (EOG). Optical coherence tomography angiography (OCTA) and BEST1 gene sequencing were performed in selected patients. Results The age at onset was 4–35 years (mean: 18.6 years). The male-to-female ratio was 0.45. All patients were hyperopic, except one with less than one diopter myopia. EOG was abnormal in 18 cases with near-normal ERGs. Six patients did not undergo EOG due to their young age. Eighteen patients (75%) had a thick choroid on EDI-OCT, of which three had advanced angle-closure glaucoma, 15 patients were hyperopic, and eight of them had more than four diopters hyperopia in both eyes. Macular retinoschisis was observed in 46 eyes of 23 patients (95%) with cysts mostly located in the inner nuclear layer (INL) to the outer nuclear layer (ONL). Of the 18 patients who underwent FA, mild peripheral leakage was seen in eight eyes of four patients (22%). Subfoveal choroidal neovascularization (CNV) was seen in three eyes of two patients (6%) that responded well to intravitreal bevacizumab (IVB). Seven mutations of the bestrophin-1 (BEST1) gene were found in this study; however, only two of them (p.Gly34 = and p.Leu319Pro) had been previously reported as the cause of ARB based on ClinVar and other literature studies. Conclusions ARB can be presented with a wide spectrum of ocular abnormalities that may not be easily diagnosed. Pachychoroid can occur alongside retinal schisis and may be the underlying cause of angle-closure glaucoma in ARB. Our study also expands the pathogenic mutation spectrum of the BEST1 gene associated with ARB.

Electrophysiological study after ranibizumab in choroidal neovascularizat

Purpose: To study the effects of intra-vitreal injection of ranibizumab on pattern electroretinogram (PERG) and multifocal electroretinogram(MF-ERG) parameters in choroidal neovascularization and to test the retinal toxicity of ranibizumab. Method: Fifty eyes of 50 patients with subfoveal choroidal neovascularization were included in the study. Thirty (30) eyes had neovascular age related macular degeneration (nAMD) and 20 eyes had myopic choroidal neovascularization. Ranibizumab was injected intravitreal monthly for3 months. Optical Coherence Tomography Angiography (OCT) was performed at the initial and final visits. Visual acuity, Pattern and multifocal electroretinography (PERG, MFERG) were performed before and at 1,2,3,6 months after intravitreal injection. Results: There was no clinical significant reduction of parameters of either MFERG or PERG after intravitreal injection of ranibizumab. There was significant increase in visual acuity, decrease in central macular thickness ,decrease in total macular volume and improvement in the parameters of both PERG and MFERG after intravitreal injection. Conclusion: Intravitreal injection of ranibizumab is effective in treatment CNV and safe. It has no retinal toxicity since no reduction in PERG&amp; MFERG parameters. Keywords: AMD; Ranibizumab; PERG; MFERG

Dome-shaped maculopathy: a review.

First described by Gaucher and associates in 2008 in eyes with high myopia, dome-shaped maculopathy (DSM) is an anterior convex protrusion of the macula towards the vitreous cavity observable on OCT. This seems to be related to a localized scleral thickness, which might be the result of regional variation in the scleral bio-mechanical properties and the process of emmetropization causing asymmetric scleral growth. The presence of DSM can be associated with an increased risk of complications. The clinical spectrum ranges from being asymptomatic to metamorphopsia and mild-to-moderate gradual visual loss over years. Visual impairment in DSM results from retinal pigment epithelial changes, sub-foveal serous detachment, retinoschisis and myopic choroidal neovascularization. In this review, we compile and review the available information on the pathophysiology, nomenclature, classification, clinical features including imaging, differential diagnosis, complications associated with DSM and the gaps in our understanding of this entity thus far.

Efficacy and Safety of a Proposed Ranibizumab Biosimilar Product vs a Reference Ranibizumab Product for Patients With Neovascular Age-Related Macular Degeneration

Neovascular age-related macular degeneration is the leading cause of blindness in individuals 50 years or older. The availability of a ranibizumab biosimilar product (SB11) may facilitate access to an effective alternative to this treatment. To demonstrate equivalence of efficacy, similar safety, and similar immunogenicity of SB11 compared with the reference ranibizumab. This randomized, double-masked, parallel-group phase 3 equivalence study was conducted in 75 centers in 9 countries from March 14, 2018, to December 9, 2019, among 705 participants 50 years or older with neovascular age-related macular degeneration with active subfoveal choroidal neovascularization lesions. Analysis was performed on an intent-to-treat basis. Intravitreous injection of SB11 or ranibizumab, 0.5 mg, every 4 weeks through week 48. Preplanned interim analysis after all participants completed the week 24 assessment of primary efficacy end points at week 8 for change from baseline in best-corrected visual acuity (BCVA) and week 4 for central subfield thickness (CST), with predefined equivalence margins for adjusted treatment differences of -3 letters to 3 letters for BCVA and -36 μm to 36 μm for CST. Baseline and disease characteristics among 705 randomized participants (403 women [57.2%]; mean [SD] age, 74.1 [8.5] years) were comparable between treatment groups (SB11, 351; ranibizumab, 354). Least-squares mean (SE) changes in BCVA from baseline at week 8 were 6.2 (0.5) letters in the SB11 group vs 7.0 (0.5) letters in the ranibizumab group, with an adjusted treatment difference of -0.8 letter (90% CI, -1.8 to 0.2 letters). Least-squares mean (SE) changes in CST from baseline at week 4 were -108 (5) μm in the SB11 group vs -100 (5) μm in the ranibizumab group, with an adjusted treatment difference of -8 μm (95% CI, -19 to 3 μm). Incidences of treatment-emergent adverse events (231 of 350 [66.0%] vs 237 of 354 [66.9%]), including serious treatment-emergent adverse events (44 of 350 [12.6%] vs 44 of 354 [12.4%]) and treatment-emergent adverse events leading to study drug discontinuation (8 of 350 [2.3%] vs 5 of 354 [1.4%]), were similar in the SB11 and ranibizumab groups. Immunogenicity was low, with a cumulative incidence of antidrug antibodies up to week 24 of 3.0% (10 of 330) in the SB11 group and 3.1% (10 of 327) in the ranibizumab group. These findings of equivalent efficacy and similar safety and immunogenicity profiles compared with ranibizumab support the use of SB11 for patients with neovascular age-related macular degeneration. ClinicalTrials.gov Identifier: NCT03150589.