Consecutive Monthly Injections Of Ranibizumab Research Articles

Changes in foveal avascular zone area and retinal vein diameter in patients with retinal vein occlusion detected by fundus fluorescein angiography.

To investigate changes in foveal avascular area (FAZ) and retinal vein diameter in patients with retinal vein occlusion (RVO) after intravitreal ranibizumab, and to analyze the correlation between ranibizumab therapy and visual gain. This retrospective study enrolled 95 eyes of 95 patients who had accepted three consecutive monthly ranibizumab injections, including 50 branch RVOs (BRVOs) and 45 central RVOs (CRVOs). BRVOs were divided into ischemia group (n = 32) and non-ischemia group (n = 18), and CRVOs also had ischemia group (n = 28) and non-ischemia group (n = 17). Comprehensive ophthalmic examinations were performed before the first injection and after 6, 12, and 24 months. The FAZ was manually circumscribed on early-phase images of fundus fluorescein angiography. Retinal vein diameters were measured on fundus photographs. After three injections, the FAZ area was significantly enlarged firstly and then reduced in all ischemic RVOs and the non-ischemic BRVOs (p < 0.05), while the retinal vein diameter was significantly reduced firstly and then increased in all groups except for unobstructed branch veins of non-ischemic BRVOs (p < 0.05). The correlation between the FAZ area and best corrected visual acuity was statistically significant in all CRVOs (non-ischemic, r = 0.372; ischemic, r = 0.286; p < 0.01) and ischemic BRVOs (r = 0.180, p < 0.05). Spearman's correlation analysis revealed that the retinal vein diameter was significantly correlated to the larger FAZ area in obstructed branch veins of ischemic BRVOs (r = -0.31, p < 0.01), inferior temporal branch veins of non-ischemic CRVOs (r = -0.461, p < 0.01) and ischemia CRVO groups (superior temporal branch vein, r = -0.226, p < 0.05; inferior temporal branch vein, r = -0.259, p < 0.01). After three consecutive monthly ranibizumab injections, the FAZ area was enlarged and retinal vein diameter reduced with gradual recovery to near baseline from 12 months. These results suggest that ranibizumab therapy can worsen macular ischemia and prevent visual gain in the short term. It has important significance for the treatment and prognosis of RVO, although the natural course of RVO may also affect ischemia and visual gain.

Angiogenin, FGF-\u03b1, and IL-36\u03b2 have higher expression levels in aqueous humor of nAMD patients in comparison to cataract patients

BackgroundNumerous cytokines have been proven to participate in the pathogenesis of neovascular age-related macular degeneration (nAMD). The present study aimed to investigate the aqueous humor cytokine expression profile in nAMD patients before and after ranibizumab treatments in comparison to cataract patients.MethodsThis prospective study included 20 treatment-naïve nAMD eyes of 20 patients who received three consecutive monthly injections of ranibizumab. Aqueous humor samples were collected before the first (baseline), second (1 month later), and third (2 months later) injections. Controls were 20 age- and gender-matched cataract patients without any other ocular disease. The aqueous concentrations of 28 cytokines were measured using a multiplex bead assay. Central macular thickness (CMT) and maximum retinal thickness (MRT)-3 mm were measured by spectral domain optical coherence tomography (SD-OCT). The greatest linear diameter (GLD) was measured by fundus fluorescein angiography (FA).ResultsThree cytokines in aqueous humor, including angiogenin, interleukin-36β (IL-36β), and fibroblast growth factor-acidic (FGF-α) were significantly higher in nAMD patients in comparison to cataract patients, both before and after two consecutive monthly ranibizumab injections. Compared with the nAMD patients’ basal levels, two consecutive monthly ranibizumab injections effectively reduced the aqueous concentrations of VEGF-A and placental growth factor (PlGF), as well as the values of CMT, MRT-3 mm, and GLD.ConclusionsAngiogenin, IL-36β, and FGF-α have higher expression levels in nAMD patients in comparison to cataract patients, both before and after 2 months of ranibizumab therapy. These cytokines may have correlations with the pathogenesis of nAMD.

Comparison of Ranibizumab With or Without Verteporfin Photodynamic Therapy for Polypoidal Choroidal Vasculopathy

The 2-year efficacy and safety of combination therapy of ranibizumab administered together with verteporfin photodynamic therapy (vPDT) compared with ranibizumab monotherapy in participants with polypoidal choroidal vasculopathy (PCV) are unclear. To compare treatment outcomes of ranibizumab, 0.5 mg, plus prompt vPDT combination therapy with ranibizumab, 0.5 mg, monotherapy in participants with PCV for 24 months. This 24-month, phase IV, double-masked, multicenter, randomized clinical trial (EVEREST II) was conducted among Asian participants from August 7, 2013, to March 2, 2017, with symptomatic macular PCV confirmed using indocyanine green angiography. Participants (N = 322) were randomized 1:1 to ranibizumab, 0.5 mg, plus vPDT (combination therapy group; n = 168) or ranibizumab, 0.5 mg, plus sham PDT (monotherapy group; n = 154). All participants received 3 consecutive monthly ranibizumab injections, followed by a pro re nata regimen. Participants also received vPDT (combination group) or sham PDT (monotherapy group) on day 1, followed by a pro re nata regimen based on the presence of active polypoidal lesions. Evaluation of combination therapy vs monotherapy at 24 months in key clinical outcomes, treatment exposure, and safety. Polypoidal lesion regression was defined as the absence of indocyanine green hyperfluorescence of polypoidal lesions. Among 322 participants (mean [SD] age, 68.1 [8.8] years; 225 [69.9%] male), the adjusted mean best-corrected visual acuity (BCVA) gains at month 24 were 9.6 letters in the combination therapy group and 5.5 letters in the monotherapy group (mean difference, 4.1 letters; 95% CI, 1.0-7.2 letters; P = .005), demonstrating that combination therapy was superior to monotherapy by the BCVA change from baseline to month 24. Combination therapy was superior to monotherapy in terms of complete polypoidal lesion regression at month 24 (81 of 143 [56.6%] vs 23 of 86 [26.7%] participants; P < .001). Participants in the combination group received fewer ranibizumab injections (median, 6.0 [interquartile range (IQR), 4.0-11.0]) than the monotherapy group (median, 12.0 [IQR, 7.0-17.0]) up to month 24. The combination group required a median of 2.0 (IQR, 1.0-3.0) vPDT treatments for 24 months, with 75 of 168 participants (44.6%) requiring only 1 vPDT treatment. The 24-month data findings confirm that ranibizumab therapy, given as monotherapy or in combination with vPDT, is efficacious and safe for treatment of PCV. Combination therapy with vPDT added to ranibizumab achieved superior BCVA gain, increased odds of complete polypoidal lesion regression, and fewer treatment episodes compared with ranibizumab monotherapy. ClinicalTrials.gov Identifier: NCT01846273.

Intravitreal ranibizumab and dexamethasone implant injections as primary treatment of diabetic macular edema: simultaneously double protocol

PurposeTo assess the 12-month efficacy and safety of simultaneously administered intravitreal dexamethasone implant (DEX implant) and ranibizumab (simultaneous double protocol) injections in comparison with ranibizumab monotherapy as the first-line treatment of diabetic macular oedema (DMO).MethodsProspective, consecutive, clinical interventional study. Patients were randomized into two groups: 24 naive DMO patients (34 eyes) who received simultaneous double-protocol therapy and 22 DMO patients (34 eyes) who received ranibizumab monotherapy were included. Monthly ranibizumab (0.5 mg) was administered for the first 6 months and later on, an as-needed treatment basis. DEX implant injection was performed at any time during the loading dose of the three consecutive monthly injections of ranibizumab, and with as-needed reinjections of ranibizumab from 6th month onwards. Change in visual acuity was the primary efficacy endpoint. Secondary efficacy endpoints were a gain of ≥15 letters and a change in the central foveal thickness.ResultsMean BCVA increased from baseline to month 12 in the simultaneously double-protocol therapy group compared with the ranibizumab monotherapy group (21.6 versus 9.6 letters [P < 0.001]). The corresponding proportions of eyes gaining ≥15 letters were 60% versus 29.4% (P < 0.0001). Moreover, the mean reductions in the central foveal thickness were 413 versus 282 µm (P = 0.001). At 12 month, the simultaneous double-protocol therapy decreased a significant number of foveal cysts and subfoveal neuroretinal detachment compared with those by ranibizumab monotherapy.ConclusionsThe simultaneous addition of DEX implant at any time during the three monthly loading doses of ranibizumab in patients with DMO significantly improved the visual outcomes and revealed superior anatomic outcomes than those with the ranibizumab monotherapy.

Early and Late Switch from Ranibizumab to an Intravitreal Dexamethasone Implant in Patients with Diabetic Macular Edema in the Event of a Poor Anatomical Response.

Patients with diabetic macular edema may not have optimal outcomes even with monthly ranibizumab intravitreal injections. A corticosteroid implant might be considered in such patients. The objective of this study was to compare the outcomes of switching from ranibizumab to an intravitreal dexamethasone implant after three or six consecutive monthly injections of ranibizumab. Patients with treatment-naïve diabetic macular edema who showed a poor anatomical response to three or six consecutive intravitreal ranibizumab injections and received an intravitreal dexamethasone implant were enrolled in this retrospective study. Patients were divided into two groups as early- and late-switch groups. The early-switch group consisted of the patients who initially received three consecutive monthly ranibizumab injections and the late-switch group consisted of the patients who initially received six consecutive monthly ranibizumab injections and switched to a dexamethasone implant because of a poor anatomical response. Best corrected visual acuity and central retinal thickness at the baseline and 3, 6, 9, and 12months in the study population were recorded. Sixty-eight eyes of 68 patients were included. The early-switch group consisted of 34 eyes and the late-switch group consisted of 34 eyes. The mean change in best corrected visual acuity was similar between the two groups at 3, 9, and 12months; however, it was significantly better in the early-switch group than the late-switch group at 6months. The change in central retinal thickness was similar between the two groups at 3, 9, and 12months; however, it was significantly better in the early-switch group than the late-switch group at 6months. Although both early switching and late switching are similar in terms of providing functional and morphological improvement, early switching appeared better for ensuring patient well-being in the early period and improving patient adherence.

Comparison of the effect of ranibizumab and dexamethasone implant in diabetic macular edema with concurrent epiretinal membrane

To compare the efficacy and safety of intravitreal ranibizumab (RZB) injections and intravitreal dexamethasone (DEX) implant in diabetic macular edema (DME) with concurrent epiretinal membrane (ERM). This was a retrospective, observational, comparative study. Medical records of DME patients with concurrent ERM were retrospectively reviewed. Seventeen eyes of 16 patients treated with 3 consecutive monthly RZB injections (RZB group) and 22 eyes of 18 patients treated with a DEX implant (DEX group) were included. The groups were compared at baseline, 1st, 2nd, 3rd and 4th months in terms of best-corrected visual acuity (BCVA), central macular thickness (CMT), and intraocular pressure (IOP). Eighteen of the 39 eyes (46.1%) were phakic at baseline, 9 (52.9%) of which were treated with RZB, whereas 9 (40.9%) were treated with DEX implant (P=0.528). Although CMT improved significantly in both the RZB and DEX groups (P<0.001); the trend was different (P=0.003). The mean change in CMT at 1month in the DEX group was greater (DEX: 188.2±142.7μm; RZB: 95.7±110.7μm; P=0.034); it was in favor of RZB group at the 3rd and 4th months (DEX: -52.7±86.9μm; RZB: 1.4±31.4μm; P=0.012. DEX: -63±67.3μm; RZB: -5.8±43.9μm; P=0.004, respectively). BCVA improved significantly in both groups (P<0.001). There was no statistical difference between the groups with regard to gain in BCVA or IOP change throughout the study period (P=0.572, P=0.064, respectively). Both RZB and DEX are effective in improving anatomical and visual outcomes in DME with concurrent ERM. The DEX group was associated with a prompt anatomic response, but with a gradual decrease from 3rd month.

Comparison of Intravitreal Aflibercept and Ranibizumab following Initial Treatment with Ranibizumab in Persistent Diabetic Macular Edema.

Purpose To compare the visual and anatomic outcomes in patients with persistent diabetic macular edema (DME) who switched from ranibizumab to aflibercept with those who continued with previous ranibizumab therapy. Methods In this retrospective comparative study, medical records of consecutive patients with center-involved DME ≥ 350 μm who had at least three recent consecutive monthly ranibizumab injections followed by as-needed therapy with either aflibercept or ranibizumab were reviewed. Data were collected at presentation (preinjection), at the intermediary visit, and at the last visit (at the end of the follow-up period). Results Forty-three eyes of 43 patients were divided into two groups: the switch group (n = 20) and the ranibizumab group (n = 23). Though no significant improvement was found in the mean BCVA from the intermediary visit to the last visit, there was a difference in the mean CMT in the switch group and the ranibizumab group (p < 0.001 and p = 0.03, resp.). The mean CMT decreased after the intermediary visit by 188.6 ± 120.5 μm in the switch group and by 60.3 ± 117.1 μm in the ranibizumab group (p = 0.003). Conclusions Both aflibercept and ranibizumab decreased CMT in patients with persistent DME who showed a poor response to ranibizumab injections. However, switching to aflibercept provided only morphologic improvement.

Change in choroidal thickness after intravitreal injection for treatment of neovascular age-related macular degeneration: Ranibizumab versus aflibercept

To compare the changes in subfoveal choroidal thickness after intravitreal ranibizumab or aflibercept injections for neovascular age-related macular degeneration (nAMD). In this retrospective study, 28 eyes with nAMD treated with 3 consecutive monthly injections of ranibizumab (IVR) and 24 eyes with nAMD treated with 3 consecutive monthly injections of aflibercept (IVA) between September 2012 and June 2016 were reviewed. The follow-up time was 6 months. Changes in two groups' best-corrected visual acuity (BCVA) and subfoveal choroidal thickness by using enhanced depth imaging optical coherence tomography at 1st, 3rd and 6th months were recorded and compared. Choroidal thickness decreased significantly in eyes treated with IVR (P=0.015, 0.01 and 0.01, respectively) or IVA (P=0.001, 0.001 and ˂0.001, respectively) at 1, 3 and 6 months examination but IVA treated eyes presented a significantly further reduction in choroidal thickness when compared with ranibizumab (P=0.03, 0,04 and 0.03, respectively). There was no significant difference between aflibercept and ranibizumab group when change in BCVA from baseline compared at 1, 3 and 6th months (P=0.54, 0.06 and 0.37, respectively). There was no correlation between change in choroidal thickness and the BCVA outcomes in either group. Subfoveal choroidal thickness decreased significantly after both of IVR and IVA injections in patients with nAMD. In conclusion, intravitreal injections of ranibizumab or aflibercept affect not only neovascular lesion but also the underlying choroid.

Efficacy and Safety of Ranibizumab With or Without Verteporfin Photodynamic Therapy for Polypoidal Choroidal Vasculopathy

Polypoidal choroidal vasculopathy (PCV) is a common subtype of exudative age-related macular degeneration among Asian individuals. To our knowledge, there are no large randomized clinical trials to evaluate intravitreal ranibizumab, with and without verteporfin photodynamic therapy (vPDT), for the treatment of PCV. To compare the efficacy and safety of combination therapy of ranibizumab and vPDT with ranibizumab monotherapy in PCV. A double-masked, multicenter randomized clinical trial of 322 Asian participants with symptomatic macular PCV confirmed by the Central Reading Center using indocyanine green angiography was conducted between August 7, 2013, and March 2, 2017. Participants were randomized 1:1 to ranibizumab, 0.5 mg, and vPDT (n = 168; combination therapy group) or ranibizumab, 0.5 mg, and sham PDT (n = 154; monotherapy group). All participants received 3 consecutive monthly ranibizumab injections, followed by a pro re nata regimen. Participants also received vPDT/sham PDT on day 1, followed by a pro re nata regimen based on the presence of active polypoidal lesions. Step 1 assessed whether combination therapy was noninferior (5-letter margin) to monotherapy for change in best-corrected visual acuity from baseline and superior in complete polyp regression. If noninferiority was established, step 2 assessed whether combination therapy was superior to monotherapy measured by best-corrected visual acuity change at month 12. Baseline demographics of the 322 participants were comparable between the treatment groups. Mean (SD) age of the patients was 68.1 (8.8) years, and overall, 69.9% of the patients were men. At baseline, the overall mean best-corrected visual acuity and mean central subfield thickness were 61.1 letters and 413.3 μm, respectively. At 12 months, mean improvement from baseline was 8.3 letters with combination therapy vs 5.1 letters with monotherapy (mean difference, 3.2 letters; 95% CI, 0.4-6.1), indicating that combination therapy met the predefined criterion for noninferiority as well as being superior to monotherapy (P = .01). Combination therapy was also superior to monotherapy in achieving complete polyp regression at month 12 (69.3% vs 34.7%; P < .001). Over 12 months, the combination therapy group received a median of 4.0 ranibizumab injections compared with 7.0 in the monotherapy group. Vitreous hemorrhage was the only ocular serious adverse event (combination therapy group, 1 [0.6%]; monotherapy group, 3 [2.0%]). After 12 months, combination therapy of ranibizumab plus vPDT was not only noninferior but also superior to ranibizumab monotherapy in best-corrected visual acuity and superior in complete polyp regression while requiring fewer injections. Combination therapy should be considered for eyes with PCV. clinicaltrials.gov Identifier: NCT01846273.

Changes in multiple cytokine concentrations in the aqueous humour of neovascular age-related macular degeneration after 2 months of ranibizumab therapy

PurposeTo determine changes in multiple cytokine concentrations in the anterior chamber during the induction phase of ranibizumab treatment in patients with neovascular age-related macular degeneration (AMD).MethodsThis prospective study included 48...

Influence of baseline diabetic retinopathy status on initial anatomical response of intravitreal ranibizumab therapy for diabetic macular oedema.

PurposeIntraocular vascular endothelial growth factor (VEGF) levels increases with the severity of diabetic retinopathy. Response of diabetic macular oedema (DMO) to ranibizumab is driven by VEGF suppression. We hypothesised that the initial reduction of central macular thickness by ranibizumab should be maximum in severe diabetic retinopathy until the levels of VEGF decreases to the levels observed in eyes with mild retinopathy.MethodsConsecutive patients with centre-involving DMO (central subfield thickness (CSFT)>300 μm) who had three consecutive monthly ranibizumab injections followed by as needed therapy were included. Retinopathy status was graded as mild non-proliferative diabetic retinopathy (NPDR) (G1), moderate to severe NPDR with no prior panretinal photocoagulation (G2), and treated PDR (G3).ResultsTwo hundred and thirty-nine eyes from 204 patients with a mean age of 64.9 years were included. The distribution was 31.4 G1, 32.2 G2, and 36.4% G3. Mean baseline CSFT for all eyes was 458.5±110.8 μm. Baseline CSFT for G1, G2, and G3, respectively, were 437.6±90.9, 472.3±109.8, and 464.7±124.9 μm (P=0.2155). Mean change in CSFT after three consecutive injections was 128.5±116.6 μm. The mean changes were 95.8±101.4 μm for G1, 137.2±112.9 μm for G2, and 148.9±126.9 μm for G3. The changes in CSFT between groups adjusted for baseline CSFT were statistically significant (P=0.0473). At 6 and 12 months after a mean of 4.5 and 7.7 injections, the changes between groups were no longer significant, P=0.4783 and P=0.8271, respectively.ConclusionsThe initial anatomical response of DMO with intravitreal ranibizumab injections was maximum in eyes with treated PDR, suggesting that the higher the VEGF levels, the better the response with ranibizumab.

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.

Vitrectomy with subretinal tissue plasminogen activator and ranibizumab for submacular haemorrhages secondary to age-related macular degeneration: retrospective case series of 45 consecutive cases.

PurposeTo assess the efficacy of small-gauge vitrectomy with subretinal recombinant tissue plasminogen activator (rtPA) and ranibizumab for submacular haemorrhages secondary to neovascular age-related macular degeneration (nAMD), and to identify the factors associated with visual outcome.MethodsA retrospective case series was performed, including all patients who had small-gauge vitrectomy with subretinal rtPA and ranibizumab for submacular haemorrhages secondary to nAMD. All patients received three consecutive monthly injections of ranibizumab after the surgery, and were reviewed monthly and treated on a pro re nata regime.ResultsA total of 45 eyes of 45 patients were included in the study. Mean age was 77.07±9.67 years, and 32 of 45 patients (71.1%) were women. Surgery was performed on average 6.98±5.70 days after the onset of symptoms, and patients were observed for a follow-up period of 12.9±10.8 months. On average, visual acuity improved -0.59±0.61 LogMAR between presentation and last follow-up. Visual acuity improved in 33 patients (73.3%), remained unchanged in 10 patients (22.2%), and worsened in 2 patients (4.4%). Multiple linear regression showed that patients with smaller haemorrhages (P=0.012) and prompt surgery (P=0.008) had better final visual acuities. A haemorrhage area of ≤30 mm(2) had 91.3% sensitivity and 73.3% specificity for predicting a final visual acuity ≥6/60.ConclusionSmall-gauge vitrectomy with subretinal rtPA and ranibizumab is effective for improving visual acuity in patients with submacular haemorrhages secondary to nAMD. Small haemorrhage area and prompt surgery are associated with better final visual acuity.

Choroidal Thickness Changes After Intravitreal Antivascular Endothelial Growth Factor Therapy for Age-Related Macular Degeneration: Ranibizumab Versus Aflibercept.

To compare the changes in subfoveal choroidal thickness (CT) in eyes with neovascular age-related macular degeneration (nAMD) treated with intravitreal ranibizumab or aflibercept. In this retrospective case series, the medical records of 28 patients with nAMD treated with at least 3 consecutive monthly injections of ranibizumab (0.5 mg/0.05 mL) or aflibercept (2 mg/0.05 mL) between December 2013 and June 2014 and who were followed up for at least 3 months were reviewed. Subfoveal choroidal thickness was measured using enhanced depth imaging optical coherence tomography. Choroidal thickness decreased over time in the aflibercept group, but was unchanged throughout the study in the ranibizumab group. At each time point, the decrease was significantly greater in aflibercept-treated eyes compared with ranibizumab-treated eyes (P<0.05). No significant change in best-corrected visual acuity (BCVA) was seen in either group during follow-up. There was no correlation between change in choroidal thickness and age, sex, duration of previous antivascular endothelial growth factor treatment, number of previous injections, spherical equivalent, baseline choroidal thickness, and the BCVA outcome in either group. Subfoveal choroidal thickness appeared to decrease significantly in eyes with nAMD during 3 months of aflibercept treatment. No corresponding decrease in choroidal thickness occurred in ranibizumab-treated eyes.

Ocular pulse amplitude and retinal vessel caliber changes after intravitreal ranibizumab.

The purpose of the present study was to examine the effects of intravitreal ranibizumab on ocular pulse amplitude (OPA) and retinal vessel caliber (RVC) in wet age-related macular degeneration (AMD). Thirty-two eyes of 32 wet AMD patients were included in this case series. Three consecutive monthly injections of ranibizumab were performed. The OPA was measured with the Pascal dynamic contour tonometer. RVC measurements were taken with spectral-domain optical coherence tomography. Pre-injection mean OPA value was 2.55±0.76mmHg and post-injections mean OPA value was 2.79±0.88mmHg at the last visit (p=0.10). Pre-injection mean arteriole and venule RVC were 96.7±9.4 and 125.9±8.4µm; while post-injections arteriole and venule RVC were 96.0±8.7 and 125.6±8.9µm, respectively (p>0.05). OPA and RVC are unchanged after triple intravitreal ranibizumab injections, indicating that this treatment does not significantly alter gross retina-choroidal vasculature and hemodynamics.

Low-Fluence Photodynamic Therapy versus Ranibizumab for Chronic Central Serous Chorioretinopathy: One-Year Results of a Randomized Trial

To compare the efficacy and safety between low-fluence photodynamic therapy (PDT) and the intravitreal ranibizumab in the treatment of chronic central serous chorioretinopathy (CSC). Prospective, randomized, single-center, parallel-arm, controlled trial. Thirty-four eyes of 32 patients with chronic CSC with >6 months' duration of symptoms or recurrent CSC were randomly placed into the low-fluence PDT group (n = 18) or the ranibizumab group (n = 16). The patients underwent a single session of low-fluence PDT or 3 consecutive monthly injections of ranibizumab. Rescue treatment was available from month 3 if the subretinal fluid (SRF) persisted or recurred after primary treatment; low-fluence PDT was given to the ranibizumab group and intravitreal ranibizumab to the low-fluence PDT group. The primary outcome was the proportion of eyes with complete resolution of SRF without rescue treatment. Secondary outcomes included the mean changes in logarithm of the minimum angle of resolution best-corrected visual acuity (BCVA), central retinal thickness (CRT), and angiographic findings from baseline to 12 months. At month 12, 16 eyes (88.9%) of the low-fluence PDT group maintained complete resolution of SRF without rescue treatment versus 2 eyes (12.5%) in the ranibizumab group (P <0.001). Two eyes (11.1%) in the low-fluence PDT group and 11 eyes (68.8%) in the ranibizumab group met the criteria for rescue treatment (P = 0.001). In the low-fluence PDT group, the mean decrease in CRT from baseline was significantly greater than that in the ranibizumab group until month 6 (P <0.05), but the differences became insignificant thereafter. The improvement in BCVA from baseline was superior in the low-fluence PDT group to that in the ranibizumab group, but the differences were not statistically significant except at month 3 (P = 0.025). On indocyanine green angiography, a significantly greater proportion of the low-fluence PDT group (16 eyes; 88.9%) showed a marked reduction in choroidal hyperpermeability after primary treatment than that of the ranibizumab group (0 eyes; P <0.001). No serious adverse events related to the drugs or procedures were observed. This study represents the overall superiority of low-fluence PDT compared with intravitreal ranibizumab in the treatment of chronic CSC.

Combination of ranibizumab and navigated retinal photocoagulation in diabetic macular edema, compared to ranibizumab mono‐therapy: Twelve month results

AbstractPurpose To evaluate the number of anti‐VEGF injections needed in DME patients using a protocol with navigated laserMethods A consecutive series of 76 eyes with DME were included and randomized into 3 groups: 1. Ranibizumab monotherapy (n=27; using an observation and retreatment paradigm for anti‐VEGF therapy that is compliant with the European Public Assessment Report (EPAR, European Medicines Agency) for ranibizumab), 2. Three consecutive monthly ranibizumab injections followed by navigated laser therapy, then application of the observation and retreatment paradigm as in group “1” (n=15), 3. Monthly ranibizumab injection until central retinal thickness (CRT) was reduced to 450µm (Spectralis OCT) then navigated laser therapy followed by the application of the observation and retreatment paradigm as in group “1” (n=34). Subjects were followed monthly (best corrected Visual acuity (BCVA), CRT) for 12month, to assess the number of anti‐VEGF injections required to maintain stable clinical improvement.Results After 12 month BCVA increased and in all three investigated groups significantly (group 1: 6.3 ±6.77; group 2: 7.1 ±8.22; group 3: 7.4 ±7.53 letters). To achieve these results, after an upload of three consecutive monthly applied ranibizumab injections, ranibizumab mono‐therapy group (group 1) needed 5.2 ± 3.2 injections. In contrast, group 2 and 3 nedded significantly less ranibizumab injections (0.5 ± 0.8 and 0.8 ± 1.1, p&lt;0.001).Conclusion Combining anti‐VEGF with navigated laser showed similar visual improvements compared to anti‐VEGF monotherapy with significantly fewer injections. Commercial interest

A prospective pilot study comparing combined intravitreal ranibizumab and half-fluence photodynamic therapy with ranibizumab monotherapy in the treatment of neovascular age-related macular degeneration

PurposeThis prospective multi-center pilot study compares the use of half-fluence photodynamic therapy combined with ranibizumab with ranibizumab monotherapy for the treatment of neovascular age-related macular degeneration.MethodsAll patients presenting with untreated subfoveal neovascular age-related macular degeneration were considered for inclusion. Patients were randomized to receive either ranibizumab with half-fluence photodynamic therapy or ranibizumab alone. Patients in the ranibizumab alone group were given three consecutive monthly ranibizumab injections and were followed monthly. They were treated with ranibizumab as needed, based on clinical discretion, using vision and optical coherence tomography. Patients in the combined group were given one same-day combined ranibizumab and half-fluence (25 j/cm2) photodynamic therapy treatment and were treated monthly as needed. Outcomes included changes in standardized visual acuity, optical coherence tomography foveal thickness, and percentage of as-needed injections to maintenance examinations.ResultsFifty-six out of 60 enrolled patients completed the twelve month primary outcome visit; this consisted of 27 patients receiving ranibizumab alone and 29 receiving combined treatment. The average age was 79.1 for the ranibizumab alone group and 79.3 for the combined group. The mean visual acuity in the ranibizumab alone group improved from 52.9 Early Treatment of Diabetic Retinopathy letters initially to 62.8 letters at twelve months. The mean visual acuity in the combined group improved from 49.2 letters to 51.8 letters at twelve months. The differences in visual acuity improvements were not statistically significant based on a two-tailed t-test (P = 0.2). Due to the presence of outliers in each group, a Mann–Whitney U test was performed to confirm the results (U = 325; P = 0.28). The mean optical coherence tomography foveal thickness improved 92.5 microns and 106.7 microns in the ranibizumab alone and the combined group, respectively. The difference was not significant based on a two-tailed t-test (P = 0.6). The ranibizumab alone group received an average of 6.8 injections, while the combined group received an average of three injections. This difference was not significant based on a chi-square test (P = 0.11).ConclusionThe groups appeared similar based on statistical analysis, but larger studies are needed to determine possible small differences between combination therapy and monotherapy.

RANIBIZUMAB MONOTHERAPY VERSUS SINGLE-SESSION VERTEPORFIN PHOTODYNAMIC THERAPY COMBINED WITH AS-NEEDED RANIBIZUMAB TREATMENT FOR THE MANAGEMENT OF NEOVASCULAR AGE-RELATED MACULAR DEGENERATION

To compare verteporfin photodynamic therapy combined with intravitreal ranibizumab (combination therapy) versus ranibizumab monotherapy for management of neovascular age-related macular degeneration. Thirty patients (40 eyes) with neovascular age-related macular degeneration were prospectively allocated to combination therapy or monotherapy. In monotherapy, the induction phase consisted of 3 consecutive monthly ranibizumab injections (0.5 mg), while the combination therapy had a single session of photodynamic therapy with intravitreal ranibizumab. Follow-up treatment for either group consisted only of additional as-needed ranibizumab injections. The main outcome measure was that a proportion of eyes losing <15 letters of visual acuity after 12 months. Except for 1 eye in combination therapy, all eyes in both groups lost <15 letters of visual acuity. At 12 months, there was a mean gain of +12 letters and +3.2 letters for monotherapy and combination therapy, respectively (relative percent change of 32% vs. 7%, P = 0.03). Anatomical improvement was similar in both groups. After induction, the time until ranibizumab retreatment was longer for combination therapy (P = 0.002) while ranibizumab injections were required more frequently with monotherapy (P = 0.015). Ranibizumab monotherapy showed greater improvement in visual acuity versus combination therapy. However, combination therapy required fewer ranibizumab injections. Larger trials need to confirm the findings of this pilot study.

Polypoidal Choroidal Vasculopathy Masquerading as Neovascular Age-Related Macular Degeneration Refractory to Ranibizumab

To report a neovascular age-related macular degeneration pattern refractory to ranibizumab. Retrospective, observational case series. Between March and May 2009, cases with neovascular age-related macular degeneration refractory to ranibizumab were investigated with indocyanine green angiography. We identified 12 eyes of 12 patients with polypoidal choroidal vasculopathy. Refractory to treatment were defined cases with persistent subretinal or intraretinal fluid, or both, after 3 or more consecutive monthly ranibizumab injections regardless of best-corrected visual acuity. All patients identified were white, of whom 6 were male. Mean age ± standard deviation at presentation was 75 ± 5.6 years (range, 64 to 81 years); diagnosis, based on fluorescein angiography, comprised occult choroidal neovascularization (CNV) in 8 eyes, and 1 case each of classic-no-occult CNV, minimally classic CNV, predominantly classic CNV, and retinal angiomatous proliferation. Eight cases had switched from courses of other therapy (5 pegaptanib, 1 photodynamic therapy, 1 photodynamic therapy then pegaptanib, 1 bevacizumab). After a mean follow-up of 10.2 ± 4.8 months (range, 3 to 18 months) and 7.6 ± 3.9 ranibizumab injections (range, 3 to 14 injections), indocyanine green angiography revealed polypoidal choroidal vasculopathy lesions in all cases. Neovascular age-related macular degeneration refractory to a course of ranibizumab injections may harbor polypoidal choroidal vasculopathy. In such cases, indocyanine green angiography is a valuable tool for revealing polypoidal lesions.