Monthly Intravitreal Ranibizumab Injections Research Articles

The Effect of Systemic Parameters and Baseline Characteristics in Short-Term Response Analysis with Intravitreal Ranibizumab in Treatment-Naive Patients with Neovascular Age-Related Macular Degeneration.

Anti-vascular endothelial growth factor drugs keep being the main therapy for neovascular age-related macular degeneration (AMD). Possible predictive parameters (demographic, biochemical and/or inflammatory) could anticipate short-term treatment response with ranibizumab. 46 treatment-naive patients were included in a prospective observational study. They underwent three monthly injections of intravitreal ranibizumab for neovascular AMD and the clinical examination was made at baseline and one month after the third injection. Demographic characteristics, co-morbidities and concomitant treatments were recorded at the baseline visit. Biochemical parameters, complete blood count and inflammation biomarkers were also measured at these times. Uric Acid was found to be statistically significant with a one-point difference between good and poor responders in both basal and treated patients, but only in basal parameters was statistical significance reached (p = 0.007 vs. p = 0.071 in treated patients). Cholesterol and inflammatory parameters such as white blood cell count and neutrophils were significantly reduced over time when treated with intravitreal ranibizumab. On the other hand, women seemed to have a worse prognosis for short-term response to intravitreal ranibizumab treatment. Uric acid may help identify possible non-responders before initial treatment with ranibizumab, and cholesterol and white blood cells could be good candidates to monitor short-term response to ranibizumab treatment.

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

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

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

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

Activation of quiescent polypoidal choroidal vasculopathy after membrane peeling vitrectomy for epiretinal membrane: a case report

BackgroundRegular membrane peeling vitrectomy for epiretinal membrane (ERM) patients seldom causes large pigment epithelial detachment (PED). We presented an unusual case of the activation of quiescent polypoidal choroidal vasculopathy (PCV) after membrane peeling vitrectomy for ERM, with an uneven therapeutic process.Case presentationA 75-year-old female patient complained of metamorphopsia in her left eye for 2 years. Her best-corrected visual acuity was 20/160 with a moderate nuclear cataract. An irregular ERM and slight PED were shown in optical coherence tomography (OCT). No obvious orange-red lesion was detected. The patient underwent vitrectomy + ERM peeling + cataract surgery. After the operation, large PED emerged, and indocyanine green angiography (ICGA) confirmed PCV. Four monthly injections of intravitreal ranibizumab were administered, but PED persisted. After focal laser therapy targeted to the polyps combined with ranibizumab treatment, PED was absorbed.ConclusionsCareful evaluation for PCV before membrane peeling vitrectomy for ERM is important, as indolent PCV may be activated postoperatively. Anti-VEGF therapy accompanied by laser photocoagulation may be more effective for PCV polyps located away from the fovea.

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.

Efficacy and Cost-Effectiveness of Anti-VEGF for Treating Diabetic Retinopathy in the Indian Population.

PurposeIn the present study, we aimed to evaluate the efficacy, safety, and cost-effectiveness of the anti-vascular endothelial growth factor (anti-VEGF), namely ranibizumab (RBZ) or bevacizumab (BVZ), after either focal or grid or scatter laser photocoagulation, for the treatment of diabetic macular edema (DME) in the Indian population.MethodsRetrospective data were collected in the Regional Institute of Ophthalmology, Kolkata, India between January 2018 and June 2019. Seventy-seven eyes received 3 consecutive monthly intravitreal injections of RBZ (0.5 mg) and were followed by prompt laser photocoagulation (within 7–10 days after the third injection). Similarly, 51 eyes received 3 consecutive monthly intravitreal injections of BVZ (1.25 mg), an off-label drug, and were followed by prompt laser therapy. Safety assessments of the therapy, as well as surrogate markers of biochemical derangements related to diabetic retinopathy (DR), were also investigated at the end of 12 months.ResultsSeventy-seven subjects who were given a treatment of RBZ+laser therapy showed average 6.87±5.53 letters gain in their best-corrected visual acuity (BCVA) score, whereas the ones treated with off-label BVZ+ laser therapy demonstrated improvement in BCVA of an average 6.82±5.76 letters in “Early Treatment Diabetic Retinopathy Study” (ETDRS) chart. The study also highlights the cost-effectiveness of both RBZ+laser and BVZ+laser therapies for the treatment of DME in DR. The results demonstrated that a subject has to pay 20.951 times more cost (in INR) for RBZ+laser therapy compared to BVZ+laser therapy, to get an almost similar outcome.ConclusionBVZ is found to be the more attractive option for treating DME in DR for its cost-friendliness over RBZ in terms of BCVA outcome, as well as the safety perspectives, at least for the economically backward population in developing countries, like India.

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.

Multifocal Electroretinogram Alterations after Intravitreal Ranibizumab Treatment in Diabetic Macular Edema.

Objectives:To assess multifocal electroretinogram (mf-ERG) values in patients with diabetic macular edema (DME) who were treated with intravitreal ranibizumab (IVR).Methods:Thirty eyes of patients with DME, who underwent three consecutive monthly injections of IVR and as required thereafter, were evaluated. Best corrected visual acuity (BCVA) (log MAR), optical coherence tomography (OCT) features [diameters of cyst and subretinal fluid, hyperreflective dots (HRDs)], and mf-ERG were evaluated at baseline, 1 month, and 6 months throughout the follow-up period. The correlation of mf-ERG values and OCT features, BCVA, and the duration of disease were investigated.Results:In the study group, the baseline P1 and N1 amplitudes were significantly lower than the control group, and P1 and N1 implicit times were significantly higher in patients with DME than in the control group in all rings (All p<0.05) The mean response density (P1 amplitude, nV/deg2) values increased over 6 months in rings 1, 2, and 3 (p<0.001, p=0.003, p=0.006). There was a negative correlation between the diameter of the cyst and the initial response density of P1 (for horizontal diameter: r=–0.658, p=0.03; for vertical diameter: r=–0.597, p=0.037; for the area of the cyst, r=–0.603, p=0.021). There was a significant negative correlation between the subretinal fluid and HRD reduction and the response density of P1 increase (all p<0.05). At baseline and 6 months, the correlation between BCVA and the P1 and N1 amplitude of the central ring was significant (for baseline P1: r=–0.649, p=0.01; for N1: r=–0.575, p=0.02; for 6-month P1, r=–0.603, p<0.001; for N1: r=–0.591, p=0.005).Conclusion:The combination of OCT and mf-ERG can be used to evaluate the functional recovery in DME.

The Application of Structural Retinal Biomarkers to Evaluate the Effect of Intravitreal Ranibizumab and Dexamethasone Intravitreal Implant on Treatment of Diabetic Macular Edema.

Background: The aim of this study was to compare the therapeutic effect of intravitreal treatment with ranibizumab and dexamethasone using specific swept-source optical coherence tomography retinal biomarkers in patients with diabetic macular edema (DME). Methods: 156 treatment-naïve patients with DME were divided in two groups: 75 patients received 3 monthly intravitreal injections of ranibizumab 0.5 mg (Lucentis®) (Group 1) and 81 patients received an intravitreal implant of dexamethasone 0.7 mg (Ozurdex®) (Group 2). Patients were evaluated at baseline (V1), at three months post-treatment in Group 1, and at two months post-treatment in Group 2 (V2). Best-corrected visual acuity (BCVA) and swept source-OCT were recorded at each interval. Changes between V1 and V2 were analyzed using the Wilcoxon test and differences between the two groups of treatment were assessed using the Mann–Whitney test. Multiple regression analysis was performed to evaluate the possible OCT biomarker (CRT, ICR, CT, SND, HRS) as predictive factors for final visual acuity improvement. Results: In both groups, BCVA improved (p-value < 0.0001), and a significant reduction in central retinal thickness, intra-retinal cysts, red dots, hyper-reflective spots (HRS), and serous detachment of neuro-epithelium (SDN) was observed. A superiority of dexamethasone over ranibizumab in reducing the SDN height (p-value = 0.03) and HRS (p-value = 0.01) was documented. Conclusions: Ranibizumab and dexamethasone are effective in the treatment of DME, as demonstrated by functional improvement and morphological biomarker change. DME associated with SDN and HRS represents a specific inflammatory pattern for which dexamethasone appears to be more effective.

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...

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.

Two-Year Efficacy of Ranibizumab Plus Laser-Induced Chorioretinal Anastomosis vs Ranibizumab Monotherapy for Central Retinal Vein Occlusion

Adding a laser-induced chorioretinal anastomosis (L-CRA) to current treatments for central retinal vein occlusion (CRVO) may improve outcomes and lessen therapy burdens. To determine the 2-year efficacy of intravitreal ranibizumab with an L-CRA vs ranibizumab alone for patients with macular edema caused by CRVO. In this randomized clinical trial conducted at a single university clinic from March 2012 to June 2015, 58 participants with macular edema caused by CRVO were randomized 1:1 to either an L-CRA or sham procedure at baseline. All participants received monthly intravitreal injections of ranibizumab, 0.5 mg. Data were analyzed from April 2017 to September 2017. Random assignment to L-CRA plus monthly injections of intravitreal ranibizumab, 0.5 mg, (combination group; n = 29) or to a sham L-CRA procedure plus monthly injections of intravitreal ranibizumab, 0.5 mg, (ranibizumab alone group; n = 29) for 6 months. From month 7 to month 24, participants were evaluated monthly and received an injection of ranibizumab if a loss of 5 or more letters of best-corrected visual acuity (BCVA) on ETDRS chart from previous highest score occurred or if there was evidence of residual macular edema on optical coherence tomography. Mean number of injections from month 7 to month 24, change in BCVA, and change in central subfield thickness (CST). Of the 58 included participants, 38 (66%) were men, and the mean (SD) age was 68.6 (11.8) years; participants had a mean (SD) BCVA of 57.09 (11.87) ETDRS letters (Snellen equivalent, 20/73) and a mean (SD) CST of 738.36 (175.54) μm. A successful L-CRA was created in 24 of 29 participants (83%) in the combination group. The mean number of injections from month 7 to month 24 was 3.2 (95% CI, 2.5-3.8) in the combination group and 7.1 (95% CI, 6.0-8.0) in the ranibizumab alone group. The ratio of the number of injections in the combination group compared with the ranibizumab alone group was 0.46 (95% CI, 0.36-0.61; P < .001). Mixed-effects regression modeling showed a difference in mean BCVA at 2 years between the combination and ranibizumab alone groups (combination, 70.3 letters [Snellen equivalent, 20/40]; ranibizumab alone, 61.6 letters [Snellen equivalent, 20/60]; difference, 8.8 letters; 95% CI, 0.2-17.3; P = .05). There was also a difference in CST at 2 years between the combination and ranibizumab alone groups (mean CST: combination, 303.6 μm; ranibizumab alone, 394.5 μm; difference, 90.9 μm; 95% CI, 24.3-157.5; P = .01). Four participants (14%) in the combination group required a vitrectomy for early macular traction or vitreous hemorrhage. For macular edema caused by CRVO, an L-CRA significantly reduced the number of ranibizumab injections required. anzctr.org.au Identifier: ACTRN12612000004864.

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 REVOLUTIONARY trial: A pilot study to assess the efficacy, durability, and safety of combination ranibizumab + peripheral scatter laser for macular edema secondary to branch retinal vein occlusion associated with peripheral nonperfusion on ultrawide-field angiography.

Purpose: To determine the efficacy, durability, and safety of combination intravitreal ranibizumab plus peripheral scatter laser in patients with macular edema secondary to branch retinal vein occlusion associated with peripheral retinal nonperfusion on ultrawide-field fluorescein angiography. Methods: A 12-month, randomized, controlled, prospective, single center phase I/II study of 12 treatment-naive eyes of 12 patients with visual impairment secondary to macular edema secondary to branch retinal vein occlusion associated with peripheral nonperfusion on ultrawide-field fluorescein angiography. Patients were randomized in 1:1 fashion to study and control groups. Patients in the study group received angiography-guided peripheral scatter laser treatment at baseline. All patients received six monthly intravitreal injections of ranibizumab followed by six months of observation with pro re nata treatment with ranibizumab if prespecified visual acuity or optical coherence tomography criteria were met. Results: At the 6-month primary outcome, both groups had significant improvement in mean change in best-corrected visual acuity (treatment: +16.8 letters v/s control +14.5 letters) and reduction in central foveal thickness (treatment: -207 μ m v/s control -241 μ m). Both groups also had an improvement at 12 months in mean change in best-corrected visual acuity (treatment: +19.1 letters v/s control +15.3 letters) and reduction in central foveal thickness (treatment: -282 μ m v/s control -281 μ m). The differences between groups were not statistically significant. In the 6-month observation period, the REVOLUTIONARY group had a statistically-significant fewer number of retreatments (median of 1 in the treatment group v/s 2.5 in the control group p=0.03), and there was a trend in the reduction of patients needing retreatment (67% in the treatment group v/s 100% in the control group, p=0.14). Conclusion: This pilot study suggests safety and durability of combination ranibizumab + angiography-guided peripheral scatter laser in treatment-naive patients with macular edema secondary to branch retinal vein occlusion and peripheral nonperfusion on ultrawide-field fluorescein angiography. Further investigation is warranted to demonstrate the efficacy and long-term benefit of this treatment strategy.

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.

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...

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.

VISUAL AND MORPHOLOGIC OUTCOMES OF INTRAVITREAL RANIBIZUMAB FOR DIABETIC MACULAR EDEMA BASED ON OPTICAL COHERENCE TOMOGRAPHY PATTERNS.

To evaluate the visual and morphologic outcomes of intravitreal ranibizumab (IVR) in eyes with diabetic macular edema (DME) based on the morphologic pattern on optical coherence tomography. A prospective and consecutive series of 55 eyes with DME was classified according to OCT features: diffuse retinal thickening (DRT), cystoid macular edema (CME), and serous retinal detachment (SRD). Patients received three consecutive monthly injections of IVR and as needed thereafter. The primary outcome was the number of treatments undertaken by DME type over 12 months. Best-corrected visual acuity, retinal thickness, and microstructural changes were also evaluated. The eyes were classified as DRT (n = 23), CME (16), or SRD (16). The mean number of injections over 12 months was significantly different among the groups: DRT (3.69), CME (5.33), and SRD (5.09; P = 0.028). Best-corrected visual acuity of SRD (20/60) was significantly worse than that of the other types (DRT = 20/38; CME = 20/43; P = 0.015) after 12 months. Vision gains and retinal anatomy improvement were maintained in all three types during the first year of IVR administration. Especially, DRT maintained a good response to ranibizumab in a fewer number of injections. Disruption of the photoreceptor integrity at the baseline was correlated with poorer visual outcome and occurred more frequently in SRD.

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.