Mean Central Retinal Thickness Research Articles

Treatment Effects of Switching to Faricimab in Eyes with Diabetic Macular Edema Refractory to Aflibercept

Background and Objectives: Faricimab is a vascular endothelial growth factor A and angiopoietin-2 bispecific antibody. It is a novel therapeutic approach distinct from previous anti-vascular endothelial growth factor agents. This study aimed to evaluate the efficacy of switching from aflibercept to faricimab in the treatment of diabetic macular edema (DME) refractory to aflibercept, with a specific focus on the resolution of macular edema. Materials and Methods: The medical records of 29 eyes of 21 patients with DME that were refractory to intravitreal injections of aflibercept (IVAs) and who had completed the clinical follow-up of at least four intravitreal injections of faricimab (IVFs) were reviewed. The central retinal thickness (CRT), best-corrected visual acuity (BCVA), and the mean period (weeks) until the next injection were measured after the second-to-last IVA, first-to-last IVA, last IVA, and first to fourth IVFs following the transition to IVF. Results: The mean time from the first IVF to the assessment of effectiveness was significantly shorter than the time to the last IVA; however, no significant difference was found in the time from the second, third, and fourth IVFs to the assessment. The mean CRTs after the first and second IVFs were not significantly different from the CRT after the last IVA, but the mean CRT after the third and fourth IVFs was significantly thinner than that after the last IVA (p = 0.0025 and p = 0.0076, respectively). The mean BCVAs after the third and fourth IVFs significantly improved compared with that after the last IVA (p = 0.0050 and p = 0.0052, respectively). Conclusions: When switching the treatment to IVF for eyes with IVA-resistant DME, better treatment outcomes are achieved if IVF is performed three or more times.

Effects of Combination Therapy with Intravitreal Ranibizumab and Tissue Plasminogen Activator for Neovascular Age-Related Macular Degeneration.

Background: Subretinal hyper-reflective material (SHRM) sometimes causes vision loss in spite of anti-vascular endothelial growth factor (VEGF) therapy in eyes with neovascular age-related macular degeneration (nvAMD). We evaluated the impacts of combination therapy with intravitreal ranibizumab (IVR) and tissue plasminogen activator (tPA) in eyes with nvAMD accompanying SHRM. Methods: In total, 25 eyes of 25 patients (16 men and 9 women, 76.7 years old), who underwent IVR/tPA for nvAMD with SHRM and were followed up for at least 12 months, were retrospectively reviewed. In total, 15 eyes were treatment-naïve and 10 eyes had previous treatment for nvAMD. Results: In total, 16 eyes had type 2 macular neovascularization (MNV), 5 eyes type 1 MNV with fibrovascular pigment epithelial detachment and 4 eyes polypoidal choroidal vasculopathy. At month 12, SHRM regressed or reduced in 18 eyes (72%) and the best-corrected visual acuity (BCVA) improved in 6 eyes (24%) and was unchanged in 14 eyes (56%), while the mean BCVA was just stabilized. The mean central retinal thickness, macular volume and SHRM thickness significantly improved from 408 µm to 287 µm, from 11.9 mm3 to 9.6 mm3, from 369 µm to 165 µm, respectively (p < 0.01). Conclusions: The combination therapy with IVR/tPA for nvAMD with SHRM may help preserve vision by prompt regression of SHRM.

Brolucizumab in recalcitrant neovascular age-related macular degeneration-real-world data in Chinese population.

This retrospective study aimed to determine the short-term efficacy and safety of brolucizumab treatment for recalcitrant neovascular age-related macular degeneration (nAMD) in a real-world setting in Taiwan. Recalcitrant nAMD patients who were treated with brolucizumab from November 2021 to August 2022 at Taipei Veterans General Hospital were included. Patients were followed for 3 months after switching to brolucizumab. The primary outcomes were changes in mean best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline to the third month. The secondary outcomes included the incidence of intraocular inflammation (IOI), proportion of patients with subretinal and intraretinal fluid (SRF and IRF), and change in pigment epithelial detachment (PED) height from baseline to the third month. The significance level was considered as p < .05 in all tests. A total of 38 patients (40 eyes) with a mean (±SD) age of 76.3 (±10.84) years were included. The baseline BCVA was 0.92±0.64 logMAR, and the CRT and PED height were 329.0±171.18 and 189.8±114.94 um, respectively. The patients had a significant reduction in CRT and resolution of IRF and SRF from baseline to the third month. There were numerical improvements in mean BCVA and PED height, but they were not significant. The percentages of achieving at least 0.1, 0.2, and 0.3 logMAR (equivalent to 5, 10, 15 ETDRS letters) visual gain were 50%, 37.5%, and 30%, respectively, during the first 3 months of follow-up. No IOI occurred in these patients. This study demonstrated that brolucizumab had good short-term structural and functional efficacy in recalcitrant nAMD patients.

Short-term effect of intravitreal dexamethasone implant in refractory diabetic macular edema

PurposeTo evaluate the short-term effects (hours-days) of intravitreal dexamethasone implant (IDI) in eyes with diabetic macular edema (DME) refractory to anti-vascular endothelial growth factor (VEGF) injections.MethodsThis was a prospective, single-arm, interventional clinical series. Eyes with DME and 3–9 injections of ranibizumab without a good response were included. Patients underwent a single IDI. Best-corrected visual acuity (BCVA) measurement, complete ophthalmic evaluation, and spectral-domain optical coherence tomography (SD-OCT) were performed at baseline, 2 h, 3 h, 24 h, 7 days, and 1 month. The main outcomes were change in central retinal thickness (CRT) on SD-OCT and BCVA.ResultsFifteen eyes of 15 patients were included. Mean CRT decreased after treatment from 515.87 µm ± 220.00 µm at baseline to 489.60 µm ± 176.53 µm after 2 h (p = 0.126), and 450.13 µm ± 163.43 at 24 h (p = 0.006). Change in BCVA was from 0.85 ± 0.44 logMAR baseline to 0.58 ± 0.37 log MAR at 1 month (p = 0.003).ConclusionsEyes treated with IDI showed significant decrease in CRT detectable 1 day after injection. In some patients, the effect could be observed 3 h post-implantation.Trial registrationClinicaltrials.gov NCT05736081. Registered 20 February 2023, Retrospectively registered.

Clinical Features Related to OCT Angiography Artifacts in Patients with Diabetic Macular Edema

To investigate the frequency and type of artifacts on optical coherence tomography angiography (OCT-A) images and the relationship with clinical features in eyes with diabetic macular edema (DME). Retrospective, cross-sectional comparative study. 192 eyes of 140 patients with DME were included. Medical records, optical coherence tomography (OCT) and OCT angiography (OCT-A) images (Spectralis, Heidelberg, Germany) and ultra-widefield color fundus photos (Optos California, Optos plc, UK) were evaluated. The frequency of artifact types (segmentation, motion, projection artifact and low signal) was determined. The relationship between artifact types and clinical features such as best corrected visual acuity (BCVA), mean central retinal thickness (CRT), foveal avascular zone (FAZ) area, perimeter, circularity index, perfusion density (PD), vessel density (VD), fractal dimension (FD) in the superficial capillary plexus (SCP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP) and flow voids in the choriocapillaris (FV), presence of hard exudate (HE) and cataract were determined. The mean age was 71.6±11.4 years, and 86 out of 140 (61.4%) were males. Artifacts were present in 63 (32.8%) of 192 eyes. 29 (15.1%) eyes had segmentation artifacts, 12 (6.3%) motion artifacts, 11 (5.7%) projection artifacts and 18 (9.4%) had low signal. BCVA, PD, VD, FD in ICP and DCP were significantly lower; and CRT, FAZ area and perimeter in ICP and DCP, presence of cystoid macular edema (CME), HE, and cataract were higher in eyes with artifacts versus eyes without artifacts (p<0.05 for each). Multivariate linear regression analysis showed a significant association between segmentation artifacts and decreased BCVA (Odds ratio (OR)=5.277, p= 0.024), increased CRT (OR=1.015, p<0.001), increased area of FAZ in DCP (OR=6.625 p=0.02), and increased perimeter of FAZ in DCP (OR=1.775 p<0.04); projection artifacts and presence of HE (OR=2.017, p=0.017); motion artifacts and presence of cataract (OR= 4.102, p= 0.01). OCT-A artifacts were present in one-third of DME eyes with segmentation artifacts being the most frequent type. Determining OCT-A artifacts is crucial to ensure accurate clinical evaluation. This data could help in developing more standardized clinical protocols for image acquisition and interpretation used in clinical practice and research.

Comparison of retinal thickness measurements among four different optical coherence tomography devices

We sought to compare the retinal thickness measurements collected using different optical coherence tomography (OCT) devices. This prospective study included 21 healthy cases, and the retinal thickness was measured using the PLEX Elite (Carl Zeiss Meditec, Dublin, California, USA), DRI OCT-1 Atlantis (Topcon Corp, Tokyo, Japan), Cirrus 5000 HD-OCT (Carl Zeiss Meditec), and Spectralis OCT (Heidelberg Engineering, Heidelberg, Germany), respectively. The mean central retinal thickness (CRT) and mean retinal thickness of the Early Treatment of Diabetic Retinopathy Study (ETDRS) area were compared. The CRT varied significantly among the different OCT devices (P < 0.001). Post-hoc analysis revealed that the CRT measured using PLEX Elite (278.95 ± 20.04 µm) and Spectralis (271.86 ± 17.92 µm) were similar, and both were greater than the CRT measurements of DRI OCT-1 (239.57 ± 21.06 µm) and Cirrus (256.76 ± 17.82 µm). Additionally, the mean retinal thickness in each ETDRS area showed significant differences among the four devices (all P < 0.001). The mean retinal thickness measured varied according to the device used, and this needs to be considered when comparing retinal thickness measurements taken with different devices.

The Effect of a Loading Dose Regimen in the Switch to Brolucizumab for Patients with Aflibercept-Resistant nAMD.

To evaluate the one-year outcomes of switching to brolucizumab with and without a loading dose regimen (three monthly injections) in eyes with aflibercept-resistant neovascular age-related macular degeneration (nAMD). We retrospectively studied nAMD patients who had retinal exudate under bimonthly injections of aflibercept and were switched to brolucizumab from aflibercept. Patients were grouped into intravitreal brolucizumab injection (IVBr) with a loading dose regimen (loading group) and without a loading dose regimen (nonloading group). We assessed the best-corrected visual acuity (BCVA), central retinal thickness (CRT) at the fovea, subfoveal choroidal thickness (SFCT), IVBr status (number of injections and last injection interval), and retinal exudate status on optical coherence tomography. Overall, 52 eyes received ≥1 IVBr; 26 eyes received ≥3 IVBr with 12-month follow-up. A total of 13 eyes in the loading group and 13 eyes in the nonloading group were reviewed. One year after switching, BCVA changed from 0.28 ± 0.25 to 0.19 ± 0.28 in the loading group (P=0.28) and from 0.25 ± 0.20 to 0.23 ± 0.25 in the nonloading group (P=0.92). The mean CRT decreased from 263.6 ± 40.7 µm to 221.7 ± 54.6 µm in the loading group (P=0.03), while it only changed from 244.9 ± 77.2 µm to 221.0 ± 78.7 µm in the nonloading group (P=0.26). Both the loading and nonloading groups achieved 69% dry macula. The number of injections received was significantly higher in the loading group (7.6 ± 0.6 vs. 6.8 ± 0.4, P  <  0.001). Two patients (4.2%) developed intraocular inflammation. Switching to brolucizumab from aflibercept for eyes with nAMD with resistance to bimonthly injections of aflibercept is a valuable treatment option with and without the loading regimen. This trial is registered with UMIN000023676.

Retinal capillary plexus in Parkinson's disease using optical coherence tomography angiography.

To evaluate the alterations of the retinal microvasculature and foveal avascular zone in patients with Parkinson's disease (PD) using optical coherence tomography angiography (OCT-A). A retrospective study of PD patients examined in the Ophthalmology Department of the General Hospital of Athens, "Georgios Gennimatas" from March 2021 to March 2022 was conducted. Totally 44 patients with PD were included and 18 healthy controls were examined, hence a total of 124 eyes were enrolled in the study. The foveal and parafoveal superficial and deep capillary plexus vascular density (fSCP-VD, fDCP-VD, pSCP-VD, pDCP-CD) and foveal avascular zone (FAZ) were quantified with OCTA. Optical coherence tomography (OCT) was used to measure macular thickness. Our statistical analysis was conducted by using a mixed effect linear regression model. After adjustment for age and gender, the mean parafoveal superficial capillary plexus vascular density (pSCP-VD) and mean parafoveal deep capillary plexus vascular density (pDCP-VD) were significantly decreased in individuals with PD (P<0.001 in both) by -2.35 (95%CI -3.3, -1.45) and -7.5 (95%CI -10.4, -4.6) respectively. fSCP-VD and fDCP-VD didn't approach statistical significance. The FAZ area and perimeter were significantly decreased (P<0.001 in both) by -0.1 mm2 (95%CI -0.13, -0.07) and -0.49 mm2 (95%CI -0.66, -0.32) respectively. Circularity didn't approach statistical significance. Central retinal thickness (CRT) was significantly decreased in individuals with PD (P<0.001) by -23.1 µm (95%CI -30.2, -16) and temporal retinal thickness (TRT) was decreased (P=0.025) by -11 µm (95%CI -22, -1.5) while nasal retinal thickness (NRT) only approached statistical significance (P=0.066). The mean pSCP-VD, pDCP-VD, CRT and TRT are significantly decreased and FAZ is altered in individuals with PD. These findings can be potentially used as biomarkers for the diagnosis and evaluation of early PD.

Comparison of Loading Dose between Aflibercept and Faricimab for Neovascular Age-Related Macular Degeneration.

Recently, faricimab was approved as the new drug for neovascular age-related macular degeneration (nAMD). We lack the knowledge to choose between the existing drug and this new drug to use for treatment-naïve nAMD cases. In this study, we compared the functional and morphologic effects in loading dose between patients with treatment-naïve nAMD treated with either intravitreal aflibercept (IVA) or intravitreal faricimab (IVF) injection in a clinical setting. This retrospective study included 30 eyes of 28 patients who started treatment with IVA between June and September 2022 and 30 eyes of 29 patients who were administered IVF between October 2022 and March 2023. All patients received three monthly IVA or IVF. The best corrected visual acuity (BCVA), central retinal thickness (CRT), and the proportion of eyes with residual exudative change at baseline and 1,2, and 3 months after initial treatment were compared between the groups. The mean BCVA significantly improved from pre-treatment after the loading dose in the IVA group (0.46 ± 0.46-0.36 ± 0.37, p = 0.0047) but not in the IVF group (0.46 ± 0.41-0.44 ± 0.45, p = 0.60). The mean CRT significantly improved in both groups. The proportion of eyes with residual exudative change was greater in the IVF group than in the IVA group 2 months after the first treatment (p = 0.026). The analysis of cases that achieved complete resolution of exudative changes after the loading dose showed that the IVA group had a significant improvement in the BCVA, whereas the IVF group did not (p = 0.0047 and 0.20, respectively). Although both IVA and IVF significantly improved CRT, the BCVA improved significantly in the IVA group but not in the IVF group.

Treatment outcomes for maculopathy secondary to retinal vein occlusion in Afghanistan.

The objective of this study was to investigate the efficacy of intravitreal antivascular endothelial growth factor (VEGF) therapy in the treatment of macular edema secondary to retinal vein occlusion (RVO) in Afghanistan. A retrospective analysis was conducted of all RVO cases that underwent intravitreal ant-VEGF injection at the two leading hospitals in Kabul. The main outcome measures were visual acuity and central retinal thickness as determined by optical coherence tomography. Information was also collected on the distance traveled by each patient and the frequency of injections. One hundred and twenty-five eyes of 121 patients (86 males) with RVO were identified as having undergone treatment, with a mean age of 53.1 years (range 20-80). The only agent used was bevacizumab. The mean central retinal thickness reduced from 624.2 ± 24.9 μm at the baseline to 257.8 ± 5.7 μm following treatment (P < 0.001). There was a small increase in visual acuity from 1.33 LogMAR at the baseline to 1.13 LogMAR following the most recent injection (P = 0.03, paired t-test). The mean distance traveled by patients was 173.9 km (range 2-447 km). Despite the challenges of health-care provision in Afghanistan, this review shows that the use of intravitreal bevacizumab has provided an effective treatment for macular edema after RVO.

Visual and anatomical outcomes following intravitreal treatment of macular oedema secondary to retinal vein occlusion

Aims/Purpose: We sought to measure the visual and anatomical outcomes of patients treated for macular oedema secondary to retinal vein occlusion (RVO) with anti‐vascular endothelial growth factor (VEGF) medications or intravitreal steroids.Methods: We retrospectively identified eyes with RVO in our Trust treated with anti‐VEGF injections or intravitreal steroids. Patient data such as age, gender and visual acuity (VA) were obtained from electronic patient records. Central retinal thickness (CRT) was measured via optical coherence tomography (OCT). Macular perfusion and ischaemia were assessed by fundus fluorescein angiography (FFA) on initiation of treatment. VA and CRT data were obtained for 24 months from starting treatment with anti‐VEGF injections or intravitreal steroids.Results: 56 eyes (26 with branch RVO (BRVO), 22 with central RVO (CRVO) and 8 with hemi‐RVO (HRVO)) were identified and followed up for 24 months after starting anti‐VEGF treatment or intravitreal steroids. Mean change in VA at 24 months was +7.0 ± 16.3 letters among CRVO eyes and + 3.9 ± 21.3 letters among BRVO eyes, whereas for HRVO mean VA change was +20.3 ± 16.8 letters. Mean CRT decreased by 334.2 ± 163.5 μm in eyes with CRVO, 147.1 ± 193.1 μm in eyes with BRVO and 300.3 ± 118.6 μm in eyes with HRVO. Furthermore, we achieved VA stabilization or improvement in 91% of eyes treated under ‘optimal’ conditions, in line with the meta‐analysis of studies on RVO outcomes by Hunter &amp; Williams (2022).Conclusions: Current Trust protocols for intravitreal steroids and anti‐VEGF injections show good outcomes in RVO patients. Patients on treatment should be followed up regularly to minimize delays, while early treatment agent switches should be pursued if VA is dropping or macular oedema persists.ReferencesHunter A, Williams M. Long‐term outcomes for patients treated for macular oedema secondary to retinal vein occlusion: a systematic review. BMJ Open Ophthalmol. 2022;7(1):e001010. doi:10.1136/bmjophth‐2022‐001010

Safety and efficacy of intravitreal injection of conbercept for the treatment of patients with choroidal neovascularization secondary to pathological myopia: Results from the SHINY study.

To evaluate the safety and efficacy of intravitreal injections of 0.5 mg conbercept in patients with choroidal neovascularization secondary to pathological myopia (pmCNV). The 177 pmCNV patients were randomly assigned in a 3:1 ratio to receive conbercept or sham injection, respectively. The conbercept group receive conbercept intravitreal injections administered on a pro re nata (PRN) basis after 3 monthly loading doses. The sham group received three consecutive monthly sham injections and then one conbercept injection followed by PRN conbercept intravitreal injections. At month 3, the mean BCVA for the two groups were improved by 12.0 letters (conbercept group, from 54.05 letters to 66.05 letters) and 0.6 letters (sham group, from 49.77 letters to 50.33 letters), respectively (p < 0.001). The mean central retinal thickness (CRT) at month 3 in the two groups decreased 62.0 μm (conbercept group, from 348.90 μm to 286.18 μm) and 4.4 μm (sham group, from 347.86 μm to 343.47 μm) (p < 0.001). At month 9, the mean BCVA improved by 13.3 letters in the conbercept group and 11.3 letters in the sham group. The mean CRT decreased 73.6 μm in the conbercept group and 55.9 μm in the sham group (p < 0.001). The most common ocular adverse events were associated with intravitreal injections, such as conjunctival haemorrhage and increased intraocular pressure. Intravitreal injections of 0.5 mg conbercept provided improvement in visual and anatomical outcomes in pmCNV patients with low rates of ocular and nonocular safety events.

Evaluation of the retinal nerve fiber layer and choroidal thickness with optical coherence tomography in patients with psoriasis

BackgroundTo evaluate the retinal nerve fiber layer (RNFL), central retinal thickness (CRT), and choroidal thickness (CT) in patients with psoriasis. MethodsThe study included 43 patients diagnosed with psoriasis not receiving systemic treatment and 41 healthy volunteers. Spectral domain optical coherence tomography was used for retinal and choroidal thickness measurements. The mean RNFL, quadrant RNFL (superior, inferior, nasal, temporal), and CRT values were recorded. The choroidal thickness measurements were taken from the subfoveal area, towards the temporal and nasal directions from the fovea at distances of 500, 1000, and 1500 µm. ResultsThe RNFL was determined to be thinner in the superior quadrant (p=0.025), and the CT was thicker at all the measurement points (p < 0.05) in the patients with psoriasis. The CRT values were similar in both groups (p > 0.05). No correlation was determined between the parameters measured and disease duration or severity. ConclusionsThinning of the RNFL and increased CT may be a sign of choroidal microvascular changes and ganglion cell damage due to psoriasis.

Long-term outcomes of anti-VEGF treatment with 5+PRN regimen for macular edema due to central retinal vein occlusion.

To assess the long-term outcomes of treating macular edema (ME) associated with central retinal vein occlusion (CRVO) with a regimen of "5+pro re nata (PRN)". This retrospective study included 27 eyes of 27 patients with ME associated with non-ischemic CRVO (non-iCRVO group, n=15) and ischemic CRVO (iCRVO group, n=12). The eyes were treated with five consecutive intravitreal injections of conbercept or ranibizumab, followed by reinjections as needed or PRN. Retinal laser photocoagulation or intravitreal dexamethasone implants (DEX) were implemented in both groups when necessary. The best-corrected visual acuity (BCVA, logMAR) and central retinal thickness (CRT) were recorded at baseline, at 1, 2, 3, 4, 5, 6, and 12mo, and at the final visit. The efficacy rates of BCVA and CRT before and after treatment were calculated. The number of injections at each visit and the incidence of adverse events were also recorded. The patients, aged 59.4±15.1y, were followed up for 24.7±8.8mo (range: 15-42mo). After treatment, BCVA improved significantly from 1.04±0.56 logMAR at baseline to 0.59±0.36 logMAR (P=0.038) at the final visit in all patients. Both the non-iCRVO and the iCRVO groups achieved improved BCVA compared to the baseline at all visit points, but there was no statistical significance (P=0.197 and 0.33, respectively). The mean CRT was statistically reduced compared to baseline at all visit points in all the eyes and in both groups (all P<0.001). The apparent effective rate was 22.22% for BCVA and 37.04% for CRT after the first injection, 48.15% for BCVA and 62.96% for CRT after 5 consecutive injections, and 74.08% for BCVA and 100% for CRT at the end of follow up. The average number of injections in all patients was 9.0±2.4 at 12mo and 14.9±8.1 finally with no statistical significance between both groups (P>0.05). Laser treatment was applied to all eyes in the iCRVO group, while only 5 patients in the non-iCRVO group. Six patients in the non-iCRVO group and 3 patients in the iCRVO group had a drug switch. DEX was applied to 4 eyes in the non-iCRVO group and 5 eyes in the iCRVO group. The 5+PRN anti-vascular endothelial growth factor (VEGF) regimen is found to be safe and effective for both iCRVO and non-iCRVO, especially in the iCRVO group. The best regimen for such patients needs to be further investigated. Adjuvant laser therapy and DEX are necessary in some cases.

Clinical efficacy and changes of serum VEGF-A, VEGF-B, and PLGF after conbercept treating neovascular age-related macular degeneration.

To evaluate the clinical efficacy and systemic safety profile of conbercept in clinical practice on vascular endothelial growth factor (VEGF)-A, VEGF-B, and placental growth factor (PLGF) levels after intravitreal injections for the neovascular age-related macular degeneration (AMD). Thirty-five patients (35 eyes) with neovascular AMD received intravitreal injections of conbercept treatment with pro re nata protocol. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were detected before the intravitreal injection and at 1, 3, and 12mo after conbercept treatment. The levels of serum VEGF-A, VEGF-B, and PLGF were measured by enzyme-linked immunosorbent assay before the injection and 1 and 12mo after conbercept treatments. At baseline, the mean BCVA score was 39.89±14.64 letters. The mean BCVA scores were 51.03±15.78, 56.71±14.38, and 52.49±10.16 letters at 1, 3, and 12mo after conbercept treatment, and the BCVA improvements were all significant, respectively (P<0.05). At baseline, the mean CRT was 436.7±141.9 µm. At 1, 3, and 12mo after conbercept treatment, the mean CRT values were 335.1±147.8, 301.1±116.5, and 312.2±98.22 µm, and the CRT improvements were all significant, respectively (P<0.05). At baseline, 1 and 12mo after conbercept treatment, the mean levels of serum VEGF-A were 1013.8±454.3, 953.1±426.4, and 981.5±471.7 pg/mL, the mean levels of serum VEGF-B were 46.93±24.76, 42.99±19.16, and 45.32±18.76 pg/mL, the mean levels of serum PLGF at these points were 251.7±154.9, 241.3±166.7, and 245.6±147.2 pg/mL, respectively. Compared with the baseline, the levels of serum VEGF-A, VEGF-B, and PLGF did not significantly change at 1 and 12mo after conbercept treatment, respectively (P>0.05). Conbercept intravitreal injection leads to BCVA and CRT improvement, however, it does not significantly affect systemic serum VEGF-A, VEGF-B, and PLGF levels at 1 and 12mo after intravitreal injection treating neovascular AMD.

Single Center Experience with Voretigene Neparvovec Gene Augmentation Therapy in RPE65 Mutation–Associated Inherited Retinal Degeneration in a Clinical Setting

To assess the impact of baseline data on psychophysical and morphological outcomes of subretinal voretigene neparvovec (VN) (Luxturna, Spark Therapeutics, Inc.) treatment. Single-center, retrospective, longitudinal, consecutive case series. Patients with RPE65-biallelic mutation-associated inherited retinal degeneration (RPE65-IRD) treated between February 2020 and March 2022 with VN and oral immunosuppression according to the manufacturer's recommendation by one surgeon (F.G.H.). Retrospective analysis of surgical and clinical records, ancillary testing, and retinal imaging after VN therapy for RPE65-IRD. Descriptive statistics compared data at baseline up to 32 months post-treatment. Best-corrected visual acuity (BCVA), low-luminance VA (LLVA), Goldmann visual fields (GVFs), chromatic full-field stimulus threshold (FST) testing (FST), scotopic and photopic 2-color threshold perimetry (2CTP), and multimodal retinal imaging. Thirty eyes of 19 patients were analyzed (10 pediatric patients < 20 years; 20 adult patients > 20 years of age; overall range: 8-40 years) with a median follow-up of 15 months (range, 1-32). The fovea was completely or partially detached in 16 eyes, attached in 12 eyes, and not assessable in 2 eyes on intraoperative imaging. Median BCVA at baseline was better in the pediatric group (P < 0.05) and did not change significantly independent of age. Meaningful loss of BCVA (≥ 0.3 logarithm of the minimal angle of resolution [logMAR]) occurred in 5 of 18 adult eyes, and a meaningful gain (≥-0.3 logMAR) occurred in 2 of 18 adult and 2 of 8 pediatric eyes. The LLVA and scotopic 2CTP improved considerably in pediatric patients. Scotopic blue FST improved at all ages but more in pediatric patients (8/8 eyes gained ≥ 10 decibels [dB]; P < 0.05). In pediatric patients, median GVF improved by 20% for target V4e and by 50% for target III4e (target I4e not detected). Novel atrophy developed in 13 of 26 eyes at the site of the bleb or peripheral of vascular arcades. Improvements in FST did not correlate with development of chorioretinal atrophy at 12 months. Mean central retinal thickness was 165.87 μm (± 26.26) at baseline (30 eyes) and 157.69 μm (± 30.3) at 12 months (26 eyes). Eight adult patients were treated unilaterally. The untreated eyes did not show meaningful changes during follow-up. These data in a clinical setting show the effectiveness of VN therapy with stable median BCVA and mean retinal thickness and improvements of LLVA, FST, and 2CTP up to 32 months. Treatment effects were superior in the pediatric group. We observed new chorioretinal atrophy in 50% of the treated eyes. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Efficacy of Injection Interval Shortening in Neovascular Age-related Macular Degeneration with Limited Response to Bimonthly Aflibercept

Purpose: To investigate the effectiveness of shortening the injection interval to &lt; 2 months in neovascular age-related macular degeneration (AMD) with limited response to bimonthly aflibercept injections.Methods: We performed a retrospective analysis of medical records for neovascular AMD patients who received aflibercept injections with &lt; 2 month intervals (shortened injection) because of limited response to bimonthly injections. The best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were compared before and after shortened injections. The incidence of complete resolution of retinal edema was also analyzed.Results: A total of 28 patients were included, with a mean duration between diagnosis and shortened injection of 43.0 ± 20.5 months. The interval of the first shortened injection was 5 weeks in 8 eyes and 6 weeks in 20 eyes. BCVA changed from mean logarithm of minimal angle of resolution of 0.37 ± 0.21 to 0.32 ± 0.20 after shortening (&lt;i&gt;p&lt;/i&gt; = 0.075). The mean CRT reduced significantly from 389.3 ± 73.7 μm to 242.1 ± 91.9 μm after shortening (&lt;i&gt;p&lt;/i&gt; &lt; 0.001). Retinal fluids resolved completely in 11 (39.3%) eyes after a single shortened injection, and in 15 (53.6%) eyes after two or more shortened injections.Conclusions: Shortening the injection interval to &lt; 2 months had good anatomical efficacy in neovascular AMD with limited response to bimonthly aflibercept injections. However, the efficacy for improvement in visual acuity was limited. Further studies are required to investigate the long-term outcomes.

Factors Affecting Intensive Aflibercept Treatment Response in Diabetic Macular Edema: A Real-World Study.

To investigate the systemic and ocular factors that affect the response to intensive aflibercept treatment in diabetic macular edema (DME) in a real-world setting. This retrospective cohort study evaluated 30 eyes of 23 patients with DME who underwent intensive intravitreal aflibercept injections (five monthly loading doses). Treatment response was assessed by central retinal thickness (CRT) and best-corrected visual acuity (BCVA) at each monthly visit. The patients were categorized as good (<300 μm) and suboptimal (≥300 μm) responders based on CRT after the loading phase. Baseline systemic and ocular factors associated with treatment response were investigated. The mean CRT and BCVA significantly improved after five loading injections (486.87 ± 95.46 to 334.90 ± 69.47 μm and 0.51 ± 0.30 to 0.35 ± 0.25 LogMAR, respectively, all p < 0.05). During 12 months of follow-up, 16 eyes (53.33%) maintained CRT without additional treatment. Eyes with diabetes mellitus (DM) for ≥15 years, estimated glomerular filtration rate (eGFR) < 80 mL/min/1.73 m2, serum creatinine ≥ 0.95 mg/dL and potassium ≥ 4.7 mmol/L, and presence of epiretinal membrane (ERM) were more likely to have a suboptimal response to the treatment. Five monthly loading doses of intravitreal aflibercept injection provided significant anatomical and visual improvements in patients with DME. Patients with longer DM duration, lower eGFR, higher serum creatinine or potassium levels, or ERM were predisposed to a suboptimal treatment response. Individual response to intensive aflibercept treatment for DME can be predicted by these systemic and ocular risk factors.

Brolucizumab for recalcitrant macular neovascularization in age-related macular degeneration with pigment epithelial detachment.

To analyze anatomic and functional response to intravitreal brolucizumab in age-related macular degeneration recalcitrant to previous intravitreal anti-VEGF therapies. In this monocentric, one arm, retrospective study, eyes affected by neovascular age-related macular degeneration (nAMD) resistant to other intravitreally injected anti-vascular endothelial growth factor inhibitors were switched to intravitreal brolucizumab. All patients underwent ophthalmological examinations at baseline and in regular follow-up intervals. Best registered visual acuity (BRVA), Goldmann tonometry, intraocular pressure (IOP), central retinal thickness (CRT) and pigment epithelial detachment (PED) characteristics were analyzed at initiation of anti-VEGF treatment, at treatment switch, and at the end of brolucizumab loading phase. The study included 20 eyes of 18 consecutively treated patients (age: 77 ± 6 years). All eyes had macular neovascularization with PED. Previous treatments included intravitreal aflibercept, bevacizumab, and ranibizumab and had not resulted in a significant improvement in BRVA (0.5 ± 0.5 logMAR vs 0.5 ± 0.6 logMAR) or mean CRT (320 ± 60 µm vs 313 ± 83 µm) up to treatment switch to brolucizumab. At the end of the brolucizumab loading phase, there was significant improvement for both BRVA (0.3 ± 0.2 logMAR, P < 0.05) and CRT (264 ± 55 µm, P < 0.05). Under previous anti-VEGF therapy, there was a significant increase/deterioration in both PED area (2.68 mm2 to 5.18 mm2, P < 0.05) and PED volume (0.39 mm3 to 1.07 mm3, P < 0.05); however, both parameters improved after switching to brolucizumab (3.81 mm2 and 0.37 mm3, P < 0.05). Our results suggest a favourable anatomical and visual response after treatment switch to brolucizumab in patients with nAMD refractory to previous anti-VEGF agents.

Long-term surveillance provides real-world evidences of safety and effectiveness in intravitreal aflibercept treatment for age-related macular degeneration

This prospective, multicentre, postmarketing surveillance were conducted to report on the long-term safety and effectiveness of intravitreal aflibercept (IVT-AFL) treatment in clinical practice of Japanese patients with neovascular age-related macular degeneration (nAMD) who newly initiated IVT-AFL treatment. The primary outcomes were the incidence of adverse events (AEs) and of adverse drug reactions (ADRs) over 36 months. Number of injections, timing of ADR occurrence, and some effectiveness index were also summarised. A total of 3,872 patients received 7.2 ± 5.8 (mean ± standard deviation) injections, and AEs occurred in 5.73% of patients. ADRs were reported in 2.76% of patients, with ocular and nonocular ADRs in 2.07% and 0.72% of patients, respectively. Most vitreo-retinal events developed within 6 months of initial IVT-AFL treatment, and most instances of increased intraocular pressure and cerebral infarction developed after 6 months of follow-up. Mean best-corrected visual acuity and central retinal thickness were numerically better throughout the follow-up period compared with baseline. These results indicated acceptable tolerability and effectiveness of IVT-AFL treatment in patients with nAMD in clinical practice in Japan. Information regarding the risk and the timing of ADRs is valuable for safe and effective long-term treatment of patients with nAMD.Trial registration number: NCT01756248.