Monthly Intravitreal Ranibizumab Research Articles

Pharmacokinetics of the Port Delivery System with Ranibizumab in the Ladder Phase 2 Trial for Neovascular Age-Related Macular Degeneration.

IntroductionLadder was a phase 2 trial that evaluated the Port Delivery System with ranibizumab (PDS) for neovascular age-related macular degeneration. Serum and aqueous humor samples were collected to characterize the pharmacokinetics (PK) of ranibizumab delivered through the PDS.MethodsLadder was a multicenter, randomized, active treatment-controlled, phase 2 clinical trial. Patients with neovascular age-related macular degeneration (n = 220) were randomized (3:3:3:2) to PDS 10 mg/ml, PDS 40 mg/ml, PDS 100 mg/ml, or monthly intravitreal ranibizumab 0.5 mg. Serum PK samples were collected in all arms and analyzed for ranibizumab concentration using an enzyme-linked immunosorbent assay. The main PK analyses were conducted in the PK-evaluable population (n = 68), which excluded patients who received fellow eye intravitreal treatment, supplemental ranibizumab treatment, or had previous treatment with bevacizumab in either eye within 9 months of randomization.ResultsIn the PDS 10 mg/ml arm, median serum ranibizumab concentrations were below the serum trough concentration (Ctrough; 130 pg/ml) expected with monthly intravitreal ranibizumab 0.5 mg at all time points. In the PDS 40 mg/ml and 100 mg/ml arms, median serum ranibizumab concentrations were above the Ctrough expected with monthly intravitreal ranibizumab 0.5 mg (130 pg/ml) through month 3 and month 12 after implantation, respectively, and remained above the lower limit of quantification through month 15 and month 16 after implantation, respectively.ConclusionsThese PK data indicate that the implant in the PDS 100 mg/ml arm maintained ranibizumab concentrations within the range of monthly intravitreal ranibizumab 0.5 mg injections (130–2220 pg/ml) through month 12 after implantation.Trial RegistrationClinicalTrials.gov identifier, NCT02510794.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40123-022-00532-9.

Short-Term Outcomes following “Switching” to Monthly Ranibizumab in Neovascular Age-Related Macular Degeneration Showing Insufficient Response to Bimonthly Aflibercept

Results CRT and logMAR VA were 349.62 ± 223.51 μm and 0.50 ± 0.23 at the baseline and 274.69 ± 148.77 μm and 0.46 ± 0.24, 311.54 ± 192.90 μm and 0.45 ± 0.20 at 1 month after the first and third ranibizumab injections, respectively. The CRT decrease during three ranibizumab injections was statistically significant (38.08 ± 69.52 μm, p=0.033). Change in VA was not statistically significant. The percentage of eyes with SRF was 100% at baseline and 53.8%, 76.9%, and 69.2% one month after each ranibizumab injections. The percentage of eyes with IRF was 38.5% at baseline and 23.1%, 23.1%, and 15.4%, respectively, after switching. Conclusion Switching to monthly ranibizumab in nAMD showing an insufficient response to bimonthly aflibercept led to immediate anatomical improvement. It can be considered in countries where the healthcare insurance system limits the minimum injection interval of aflibercept.

Intravitreal Ranibizumab versus Intravitreal Ranibizumab Combined with Posterior Subtenon Triamcinolone Acetonide in Diabetic Macular Edema

Objectives:This is a retrospective, comparative evaluation of the short-term efficacy and safety of intravitreal ranibizumab (IVR) and IVR combined with posterior subtenon triamcinolone acetonide (STA) in the treatment of diabetic macular oedema (DME).Methods:A total of 79 pseudophakic eyes of 57 patients with DME who underwent IVR injection treatment were examined retrospectively. All of the patients were treatment-naive. In the study group (STA+IVR), consisting of 30 eyes of 39 patients, the STA and IVR were administered in the first treatment session simultaneously, followed by 2 consecutive monthly IVR injections. In the control group (IVR only) comprised 40 eyes of 27 patients, 3 consecutive monthly IVR injections were administered. Patients with serous retinal detachment (SRD) according to optical coherence tomography images were identified in both groups for subgroup analyses. The primary outcome measures were changes in central macular thickness (CMT), best corrected visual acuity (BCVA), and the intraocular pressure (IOP) at 1, 2, and 3 months post-injection.Results:There was no statistically significant difference between the demographic characteristics of the patients’ baseline BCVA and CMT measurements (p>0.05). For the IVR group, the mean pre-treatment CMT and BCVA was 421.20±89.10 μm and 0.42±0.24 logMAR, respectively. After the third injection, the mean was 308.12±59.07 μm and 0.20±0.12 logMAR, respectively. The combined treatment group baseline measurements were 454.50±122.52 μm and 0.54±0.29 logMAR, respectively. After the third injection, the mean was 294.22±50.33 μm and 0.27±0.21 logMAR, respectively. The decrease was statistically significant for both groups (p=0.001). Comparison of the CMT within groups revealed a statistically significant difference in favor of the combined group after the second injection (p=0.017). There was no statistically significant difference in the BCVA gains between groups (p>0.05). Patients with SRD were evaluated as a subgroup, and at the first month, the mean gain in CMT was -71.63±57.98 μm in the control group and -123.61±93.46 μm in the study group (p=0.048). The required anti-glaucomatous treatment was statistically significant in the combined group (p=0.008).Conclusion:Both treatments provided improvement in BCVA and CMT and can be considered functional and anatomically effective treatment options for DME.

THE CORRELATION BETWEEN AQUEOUS VASCULAR ENDOTHELIAL GROWTH FACTOR LEVEL AND CLINICAL ACTIVITY IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

The aim of the current study was to investigate the correlation between the pretreatment aqueous level of vascular endothelial growth factor (VEGF) and clinical activity in neovascular age-related macular degeneration. Patients with neovascular age-related macular degeneration treated by intravitreal ranibizumab injections and followed for 12 months were included in the current study. The treatment regimen consisted of three consecutive monthly intravitreal ranibizumab injections (loading treatment) followed by a pro re nata (PRN) treatment regimen. The aqueous VEGF levels were measured by enzyme-linked immunosorbent assay using aqueous humor samples obtained just before the first intravitreal ranibizumab injections. Sixty-four eyes of 64 patients were included in the current study. The mean number of intravitreal ranibizumab injections during 12 months was 4.6 ± 1.4, and 17 eyes had no recurrence after loading treatment. The mean aqueous VEGF level was significantly higher in eyes with recurrence after loading treatment than in eyes without recurrence (107.6 vs. 83.8 pg/mL, respectively; P = 0.04) and significantly higher in eyes with recurrence within 3 months after loading treatment than in other eyes (114.9 vs. 86.7 pg/mL, respectively; P < 0.01). Pretreatment aqueous VEGF level was significantly correlated with the likelihood of recurrence in neovascular age-related macular degeneration. The measurement of pretreatment aqueous VEGF level may be useful to determine the best treatment options for patients with neovascular age-related macular degeneration.

Anatomical and functional outcomes following switching from aflibercept to ranibizumab in neovascular age-related macular degeneration in Europe: SAFARI study

Background/AimsProspective data on switching anti-vascular endothelial growth factors in patients with neovascular age-related macular degeneration (nAMD) who have previously shown no/partial response are limited. This prospective study assessed the effect...

The Port Delivery System with Ranibizumab for Neovascular Age-Related Macular Degeneration: Results from the Randomized Phase 2 Ladder Clinical Trial

To evaluate the safety and efficacy of the Port Delivery System with ranibizumab (PDS) for neovascular age-related macular degeneration (nAMD) treatment. Phase 2, multicenter, randomized, active treatment-controlled clinical trial. Patients diagnosed with nAMD within 9 months who had received 2 or more prior anti-vascular endothelial growth factor intravitreal injections and were responsive to treatment. Patients were randomized 3:3:3:2 to receive the PDS filled with ranibizumab 10 mg/ml, 40 mg/ml, 100 mg/ml, or monthly intravitreal ranibizumab 0.5-mg injections. Time to first implant refill assessed when the last enrolled patient completed the month 9 visit (primary efficacy end point), improvement in best-corrected visual acuity (BCVA) and central foveal thickness (CFT), and safety. The primary analysis population was 220 patients, with 58, 62, 59, and 41 patients in the PDS 10-mg/ml, PDS 40-mg/ml, PDS 100-mg/ml, and monthly intravitreal ranibizumab 0.5-mg arms, respectively. Median time to first implant refill was 8.7, 13.0, and 15.0 months in the PDS 10-mg/ml, PDS 40-mg/ml, and PDS 100-mg/ml arms, respectively. At month 9, the adjusted mean BCVA change from baseline was ‒3.2 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, ‒0.5 ETDRS letters,+5.0 ETDRS letters, and+3.9 ETDRS letters in the PDS 10-mg/ml, PDS 40-mg/ml, PDS 100-mg/ml, and monthly intravitreal ranibizumab 0.5-mg arms, respectively. At month 9, the adjusted mean CFT change from baseline was similar in the PDS 100-mg/ml and monthly intravitreal ranibizumab 0.5-mg arms. The optimized PDS implant insertion and refill procedures were generally well tolerated. After surgical procedure optimization, postoperative vitreous hemorrhage rate was 4.5% (7/157; 1 event classified as serious). There was no evidence of implant clogging. In the phase 2 Ladder trial, the PDS was generally well tolerated and demonstrated a dose response across multiple end points in patients with nAMD. The PDS 100-mg/ml arm showed visual and anatomic outcomes comparable with monthly intravitreal ranibizumab 0.5-mg injections but with a reduced total number of ranibizumab treatments. The PDS has the potential to reduce treatment burden in nAMD while maintaining vision.

Dexamethasone implant as an adjuvant therapy to ranibizumab loading dose in persistent diabetic macular edema.

This study evaluates the effectiveness of a single-dose dexamethasone implant (DI) as an auxiliary therapy to continued intravitreal ranibizumab (IVR) treatment in patients with persistent diabetic macular edema (DME). Twenty-five pseudophakic eyes of 25 patients with DME who underwent a single injection of DI as an adjuvant therapy following an IVR loading dose were examined retrospectively. All patients were treatment naive and had a poor response to a loading dose of three consecutive monthly IVR injections. IVR treatments were continued pro re nata after the DI. The main outcome measures were changes in best-corrected visual acuity (BCVA) and central macular thickness (CMT) at 1, 3, 6 and 8 months post-DI treatment. After the IVR loading dose, the mean BCVA and CMT were 0.9 ± 0.6LogMAR and 478.2 ± 107.8µm, respectively. One month after the DI, the mean BCVA and CMT had improved to 0.6 ± 0.4LogMAR (p = 0.005) and 313.8 ± 62.7µm (p < 0.001), respectively. This improvement was maintained with mean 0.8 ± 0.8 IVR injections throughout the follow-up period. The final mean BCVA and CMT were 0.5 ± 0.5LogMAR and 298.4 ± 71.5µm. Subgroup analyses revealed that different DME types did not have any effect on CMT or BCVA improvement (p = 0.188, p = 0.136; respectively). Adding DI results in rapid anatomical and visual improvement in patients who respond poorly to an IVR loading dose. Improvements may be maintained with additional IVR in follow-up.

Comparison of one and three initial monthly intravitreal ranibizumab injection in patients with macular edema secondary to branch retinal vein occlusion.

To compare three initial monthly intravitreal ranibizumab (IVR) injections followed by pro re nata (PRN) dosing with one initial monthly IVR injections followed by PRN dosing for macular edema (ME) secondary to branch retinal vein occlusion (BRVO). Forty-two eyes of 42 patients who had IVR injections for BRVO were retrospectively studied. Eighteen eyes received 1 initial IVR injection (1+PRN group) and 24 eyes received 3 monthly IVR injections (3+PRN). At 1, 3, 6 and 12mo; spectral-domain optical coherence tomography (SD-OCT) was performed. Central macular thickness (CMT), the integrity of the external limiting membrane (ELM), the presence of subretinal fluid, cyst size, the presence of inner segment/outer segment (IS/OS) defect were determined. At baseline the mean CMT was 521.3±153.2 µm in the 3+PRN group while it was 438.1±162.4 µm in 1+PRN group. At the final visit, mean CMT was 278.3±87.8 µm in the 3+PRN group and 285.2±74.2 µm in the 1+PRN group (P=0.079). The changes in CMT over the entire study period were also comparable in both groups (243±160 µm in the 3+PRN group, and 152.9±175.3 µm in the 1+PRN group; P=0.090). At baseline, best-corrected visual acuity (BCVA) was 0.92±0.60 logarithm of the minimal angle of resolution (logMAR) in the 3+PRN group, while it was 0.72±0.46 logMAR in the 1+PRN group. Final BCVA was 0.42±0.55 logMAR in the 3+PRN group and 0.38±0.50 logMAR in the 1+PRN group (P=0.979). Additionally, the BCVA changes from baseline to final visit were not significantly different (-0.50±0.45 logMAR in the 3+PRN group, and -0.33±0.39 logMAR in the 1+PRN group; P=0.255). No significant differences in the anatomical or functional results are found between 3+PRN and 1+PRN regimens in the patients receiving ranibizumab for ME secondary to BRVO. Intact IS/OS and baseline BCVA are good predictor of the visual gain, while baseline CMT is a good predictor of the anatomical gain.

The outcomes of aflibercept therapy in patients with age-related macular degeneration resistant to bevacizumab or ranibizumab

PurposeThis study was designed to assess the functional and anatomic outcomes of intravitreal aflibercept injection in patients with wet age-related macular degeneration (AMD) refractory to intravitreal bevacizumab or ranibizumab therapy. MethodsThis retrospective study included 43 eyes of 43 patients resistant to treatment with at least 6 injections of bevacizumab or ranibizumab. Persistent intraretinal and subretinal fluid (IRF and SRF) on optical coherence tomography (OCT), no improvement in best corrected visual acuity (BCVA), and a central macular thickness (CMT) increase of more than 100 μm due to SRF and/or IRF compared to baseline for at least 6 monthly intravitreal bevacizumab or ranibizumab injections were defined as resistant to bevacizumab/ranibizumab therapy. BCVA, intraocular pressure (IOP), CMT, maximum retinal thickness (MRT), and maximum pigment epithelial detachment (PED) height (MPEDH) were evaluated before and after aflibercept injections. ResultAfter initiating aflibercept treatment, the mean final BCVA logarithm of the minimum angle of resolution or recognition (logMAR) improved to 0.84 ± 0.59 which was statistically significant compared to baseline (1.14 ± 0.51), (P < 0.001). After aflibercept injection, statistically significant reduction was noted in mean CMT (402.6 ± 196.7 μm vs 264.2 ± 52.85 μm, P < 0.05), MRT (435.3 ± 195.2 μm vs 282.2 ± 31.8 μm, P < 0.05), and MPEDH (154.2 ± 86.0 μm vs 68.3 ± 70.6 μm, P < 0.05). There was no correlation between the total number of previous injections and the increase of BCVA (r = −0.10, P = 0.265). The decrease of mean IOP was statistically significant under aflibercept treatment (P < 0.001). ConclusionsThe present study showed the efficacy of aflibercept treatment in eyes with persistent retinal or SRF under bevacizumab or ranibizumab therapy. A significant anatomical and functional improvement was noted.

Inner nuclear layer cystoid spaces are a poor prognostic factor in typical age-related macular degeneration and polypoidal choroidal vasculopathy.

To investigate predictive factors for changes in best-corrected visual acuity (BCVA) at 24months after intravitreal ranibizumab (IVR) for neovascular age-related macular degeneration (nAMD). This retrospective study included 55 eyes of 55 consecutive patients (32 men and 23 women) with nAMD who received three consecutive monthly IVR injections and were re-treated as needed over a 24-month period. We used the mean changes in logarithm of the minimal angle of resolution (logMAR) BCVA at 24months as the dependent variable in regression analysis. The presence of intraretinal cystoid spaces in the inner nuclear layer (INLc, P=0.004) and baseline subfoveal choroidal thickness (SFCT, P=0.013) predicted BCVA changes from baseline to 24months. The presence of INLc and thinning of SFCT were associated with decreased BCVA at 24months. Thirty-five eyes without INLc showed improved logMAR BCVA, from 0.550±0.273 to 0.368±0.274 (P=0.045); however, 20 eyes with INLc showed decreased logMAR BCVA, from 0.708±0.347 to 0.971±0.523 (P<0.001) through the 24-month follow-up. The mean number of IVR injections during the follow-up period was 8.74±4.76 in eyes without INLc and 10.63±4.72 in eyes with INLc, without a statistically significant difference (P=0.144). Eyes with INLc or thinned SFCT showed worse visual outcomes compared with eyes without the INLc or with thick SFCT. Furthermore, eyes without INLc showed improved BCVA; however, eyes with INLc showed decreased BCVA with an as-needed regimen.

Prognostic factors of short-term outcomes of intravitreal ranibizumab in diabetic macular edema.

To evaluate the prognostic factors for short-term visual and anatomical improvement of intravitreal ranibizumab (IVR) for diabetic macular edema (DME). Fifty-one eyes from 35 patients that received three consecutive monthly IVR for DME with moderate visual loss were retrospectively recruited; all cases had their baseline best-corrected visual acuity (BCVA) between 20/400 and 20/40. BCVA and central subfield thickness (CST) at baseline and month 3 were collected. Linear mixed models were used to evaluate the prognostic factors for visual and anatomical improvement at month 3. Younger age, poorer baseline BCVA and proliferative diabetic retinopathy (PDR) were correlated with better visual improvement at month 3 (P=0.002, 0.0001 and 0.007, respectively). Thicker CST and the presence of subretinal fluid at baseline were correlated with a greater reduction in CST (P<0.0001 and P=0.018, respectively). The presence of epiretinal membrane or previous posterior subtenon injection of triamcinolone acetonide (PSTA) were associated with a smaller reduction in CST (P=0.029 and 0.018, respectively), but had no significant effects in visual improvement at month 3 (P>0.05 for both). For eyes with DME and moderate visual loss, those with younger age, poorer baseline BCVA or PDR tend to have better visual improvement after three consecutive monthly IVR. Epiretinal membrane or previous PSTA result in less resolution of CST, but do not significantly affect visual improvement.

Aqueous cytokine and growth factor levels indicate response to ranibizumab for diabetic macular oedema

Background/AimsTo investigate the relations between aqueous humour levels of cytokines/growth factors and treatment response to intravitreal ranibizumab (IVR) for diabetic macular oedema (DME)MethodsSixty-eight eyes of 68 patients with treatment-naïve centre-involved...

Systemic Associations with Residual Subretinal Fluid after Ranibizumab in Diabetic Macular Edema.

Purpose To investigate the impact of systemic diseases on the occurrence of subretinal fluid (SRF) in diabetic macular edema (DME) and prognostic factors for residual SRF following three consecutive monthly intravitreal ranibizumab. Methods Ninety-seven eyes from 68 patients with DME who completed 3 consecutive monthly injections of ranibizumab were enrolled. Systemic parameters mainly included chronic kidney disease (CKD), hypertension, HbA1c, and insulin dependence. Renal parameters for CKD were serum creatinine, estimated glomerular filtration rate (eGFR), and serum albumin. Ocular factors were baseline central macular thickness (CMT), severity of diabetic retinopathy (DR), and status of panretinal photocoagulation (PRP). Results Chronic kidney disease had significant correlation with baseline SRF (R = 0.397, p < 0.001 after partial correlation with adjustment for age and DR severity). As for CKD, lower serum albumin, but not eGFR or serum creatinine, was associated with baseline presence of SRF (p = 0.026, p = 0.08 and p = 0.53, resp., after adjustment for age and DR severity). Overall, lower eGFR and lower HbA1c values, contrary to popular belief, predicted the presence of residual SRF following intravitreal injections (p = 0.016 and p < 0.001, resp.). Conclusions Tight sugar control and poorer baseline kidney function may slow the resorption of SRF after anti-VEGF injections in patients with DME in the short term.

Comparing ranibizumab monotherapy and combination with single photodynamic therapy in wet AMD: retreatment and morphologic results.

To evaluate retreatment indications/morphologic responses to ranibizumab monotherapy and combination with verteporfin photodynamic therapy (PDT). A total of 40 patients received 3 monthly intravitreal ranibizumab 0.3 mg injections combined with either PDT or sham PDT at baseline (1:1) followed by as-needed ranibizumab based on predetermined vision/anatomical criteria. Retreatment criteria were visual acuity (VA) loss (59%/58%), central retinal thickness (CRT) increase (27%/26%), or both (14%/16%). One month before retreatment, intraretinal cysts (IRC) were present in 84%/74%, subretinal fluid (SRF) in 70%/63%, and at least one of them in 84%/89% of eyes. A significant decrease in mean leakage area, IRC, and SRF as well as a reduction in presence of hemorrhages and hard exudates occurred in both treatment groups at 12 months (compared to baseline). Retreatment indications were mostly based on VA loss, probably due to the quantitative optical coherence tomography criterion. Intraretinal cysts and SRF were earlier predictors for recurring choroidal neovascularization (CNV) activity than CRT/VA changes. Both treatment strategies were equally potent in reducing CNV activity.

Distinct Responsiveness to Intravitreal Ranibizumab Therapy in Polypoidal Choroidal Vasculopathy With Single or Multiple Polyps

To understand the prognosis of polypoidal choroidal vasculopathy (PCV) by evaluating the responsiveness to intravitreal ranibizumab (IVR) monotherapy according to the presence of a single or multiple polyps. Retrospective case series. We included 48 treatment-naïve eyes of 48 patients who received IVR monotherapy at the Medical Retina Division Clinic, Keio University Hospital between March 2009 and January 2013 and attended the clinic for at least 12months. All patients received 3monthly IVR injections followed by pro re nata injections and were divided into single polyp and multiple polyps groups according to indocyanine green angiography and optical coherence tomography (OCT) findings. The outcome measures included changes in best-corrected visual acuity (BCVA) and OCT findings over 2 years after initial IVR. At baseline, the multiple polyps group exhibited a poorer BCVA, larger greatest linear dimension, and higher prevalence of fibrovascular pigment epithelial detachment compared with the single polyp group. Over 2 years, the multiple polyps group showed no improvement in BCVA, although the central retinal thickness (CRT) decreased in both groups. The multiple polyps group exhibited a significantly greater CRT at 1 year and required more injections in the first year compared with the single polyp group; furthermore, it included a higher number of nonresponders judged either by BCVA or fundus findings at 1 year and fundus findings at 2 years. We propose that the stratification of PCV lesions according to the presence of single or multiple polyps may be valuable to understand the prognosis.

Two-year results of combined intravitreal ranibizumab and photodynamic therapy for retinal angiomatous proliferation.

The aim of this study was clarify the efficacy of combination therapy of intravitreal ranibizumab (IVR) injections and photodynamic therapy (PDT) in patients with symptomatic retinal angiomatous proliferation (RAP) over 24 months. We retrospectively reviewed 37 naïve eyes of 31 patients treated with three consecutive monthly IVR injections (0.5 mg/0.05 ml) and PDT and followed for at least 24 months. The mean logarithm of the minimum angle of resolution best-corrected visual acuity levels improved significantly (P < 0.0001) from 0.63 at baseline to 0.39 at 24 months. Geographic atrophy (GA) involving the fovea developed in nine (24%) eyes, with a significant (P = 0.036) decrease in VA at 24 months and a high (100%) prevalence of reticular pseudodrusen (RPD) at baseline. Complete occlusion of the retinal–retinal anastomosis seen in 35 eyes was achieved in 33 eyes at month 24. The central retinal thickness decreased significantly (P < 0.0001) from 415 to 129 μm at 24 months. The mean number of treatments during 24 months was 2.5 PDT and 5.5 IVR injections. Combination therapy comprising IVR injections and PDT is generally effective in maintaining or improving VA and retinal morphology within 2 years in eyes with RAP, except for eyes with baseline RPD, which are likely to develop GA in the fovea resulting in reduced VA.

The Presence of Intra- or Subretinal Fluid during the Loading Phase in the Treatment of Exudative Age-Related Macular Degeneration with Intravitreal Ranibizumab Assessed by Optical Coherence Tomography

Purpose: To assess intra- and subretinal fluid during the loading phase with intravitreal ranibizumab in exudative age-related macular degeneration and to quantify the accuracy of crosshair scan spectral-domain optical coherence tomography with regard to retinal fluid. Methods: This is a retrospective study of 31 treatment-naive patients who received 3 monthly intravitreal ranibizumab injections. Visual acuity and the presence of retinal fluid were assessed at each visit using volume and crosshair scan protocols. Results: Visual acuity improved and central retinal thickness decreased significantly during the loading phase. However, retinal fluid persisted in two thirds of the patients. The accuracy of the crosshair scan to detect fluid was 93%. Conclusions: A substantial proportion of eyes had persistent fluid after 3 months of ranibizumab injections. However, visual improvement was independent of residual fluid. Message: Crosshair scans detect relevant collections of retinal fluid accurately and may be sufficient in daily clinical practice.

Effects of Intravitreal Ranibizumab on Retinal Hard Exudate in Diabetic Macular Edema: Findings from the RIDE and RISE Phase III Clinical Trials

To evaluate the effect of monthly intravitreal ranibizumab on hard exudate (HE) area and the impact of HE on visual acuity (VA) outcomes in diabetic macular edema (DME) patients using data from 2 phase III clinical trials. Exploratory analyses of phase III, randomized, double-masked, sham-controlled, multicenter clinical trials. Adults with DME, baseline best-corrected VA 20/40 to 20/320 Snellen equivalent, and central foveal thickness of ≥275 μm. Between the 2 studies, 759 patients with DME were randomized to receive monthly 0.3 or 0.5 mg intravitreal ranibizumab (Lucentis; Genentech, Inc., South San Francisco, CA) or sham injections. Hard exudate area was assessed from color fundus stereophotographs both on an ordinal scale and using continuous estimates of areas within the Early Treatment Diabetic Retinopathy Study grid. Data from 739 eyes were available for analysis. Mean baseline HE area was similar across treatment groups, ranging from 0.65 to 0.82 mm(2). Through month 24, the percentage of eyes without HE increased from 20.9% to 36.3% in the sham group and from 22.1% to 61.3% and 23.6% to 62.0% in the ranibizumab 0.3-mg and 0.5-mg groups, respectively. Resolution of HE became apparent sometime after month 6 in ranibizumab-treated eyes. At baseline, there was no meaningful correlation between VA and presence or absence of HE. After baseline, there also was no consistent correlation between presence or absence of HE and change in VA over time. In this exploratory analysis, monthly intravitreal ranibizumab resulted in significantly greater reduction of HE area compared with sham (P < 0.0001). In contrast to the rapid effects of ranibizumab on macular edema, changes in HE area were more gradual. Contrary to prior expectations, the presence and area of HE did not increase as DME resolved (either in the ranibizumab or sham groups). Importantly, baseline VA was not correlated with presence of HE, nor was the therapeutic benefit of ranibizumab on VA affected negatively by the presence of HE. These data suggest that in the context of intravitreal anti-vascular endothelial growth factor therapy, the presence of HE is not a prognostic indicator of poor visual outcomes.

Comparison of intravitreal ranibizumab between phakic and pseudophakic neovascular age-related macular degeneration patients: Two-year results

Background and objectiveTo compare the efficacy of intravitreal ranibizumab (IVR) for the treatment of neovascular age-related macular degeneration (nAMD) between phakic and pseudophakic eyes after a follow-up of two years. Materials and methodsData were analyzed retrospectively. The newly diagnosed and treatment naïve nAMD patients were included in the study. The patients were divided into two subgroups: phakic group, and pseudophakic. All patients received 3 consecutive monthly IVR injections, and then the treatment was continued on an as-needed regimen. Patients were examined monthly, and the data at the baseline, at month 6, 12, 18, and 24 were evaluated. The changes in best corrected visual acuity (BCVA), central retinal thickness (CRT), and the number of injections were compared between the two groups. ResultsThe study included 92 eyes of 87 patients (58 phakic, 34 pseudophakic). Mean logarithm of the minimal angle of resolution (LogMAR) VA at the baseline, and at month 6, 12, 18, and 24 was 0.89, 0.74, 0.75, 0.73, and 0.75, in the phakic group; and 0.79, 0.71, 0.66, 0.70, and 0.70 in the pseudophakic group, respectively. The change in mean BCVA from the baseline to month 6, 12, 18, and 24 was not statistically different between the two groups (p=0.4, p=0.9, p=0.5, p=0.6, respectively). Mean injection number at month 24 was 7.9 and 8.1 in the phakic and pseudophakic group, respectively (p=0.7). ConclusionIntravitreal ranibizumab treatment on an as-needed treatment regimen is effective in preserving vision and improving central retinal thickness in both the phakic and pseudophakic group of nAMD patients. The functional and anatomical outcomes of the treatment, and the number of injections were similar in the phakic and pseudophakic nAMD patients after a follow-up time of 24months.

Optical coherence tomography-based ranibizumab monotherapy for retinal angiomatous proliferation in Korean patients.

To evaluate the visual outcome of optical coherence tomography-based ranibizumab monotherapy in Korean patients with retinal angiomatous proliferation and identify prognostic factors of visual outcome. A prospective single-arm clinical study of 31 retinal angiomatous proliferation patients who underwent 3 consecutive monthly intravitreal ranibizumab injections was conducted. Additional treatment was given based on optical coherence tomography at monthly follow-ups over 24 months. Best-corrected visual acuity improved from 48.7 ± 19.3 to 56.3 ± 19.1 letters at 24 months (P = 0.010). Total cumulative numbers of injection were 5.5 ± 2.2 and 7.7 ± 3.4 times at 12 and 24 months, respectively. Older age, larger choroidal neovascularization size, and poor initial best-corrected visual acuity were associated with poor visual outcome. Final best-corrected visual acuity was significantly worse with Stage 3 disease (70.4 ± 5.1, 62.3 ± 11.6, 46.2 ± 22.3 letters improved in each stage; P = 0.015). Among factors associated with poor visual outcome, only the stage of retinal angiomatous proliferation remained statistically significant on multiple linear regression analysis (P = 0.006). Although baseline best-corrected visual acuity was similar, Stage 3 patients exhibited limited visual improvement despite anatomical improvement, and more recurrences requiring more injections. Retinal angiomatous proliferation may be successfully managed with ranibizumab monotherapy in Korean patients, with the number of treatments required comparable to other forms of neovascular age-related macular degeneration. However, visual improvement was limited in late-stage RAP.