Monthly Ranibizumab Injections Research Articles

RECURRENCE IN PATIENTS WITH TYPE 3 NEOVASCULARIZATION (RETINAL ANGIOMATOUS PROLIFERATION) AFTER INTRAVITREAL RANIBIZUMAB.

To evaluate the incidence, timing, and characteristics of recurrence in patients with Type 3 neovascularization who were initially treated with ranibizumab. This retrospective study included 42 patients (42 eyes) who were diagnosed with Type 3 neovascularization and treated with 3 monthly injections of ranibizumab. The 12-month follow-up data of these patients were analyzed. The time of recurrence after the initial treatment was recorded. In eyes with recurrence, the association of the duration until the first recurrence and the incidence of multiple recurrences was analyzed. During the 12 months, recurrence was noted in 32 patients (76.2%), with 20 experiencing multiple recurrences. The first recurrence occurred (mean ± SD) 5.3 ± 1.8 months (range, 2-9 months) after the third ranibizumab injection. The first recurrence was noted in 20 eyes (62.5%) at 4 months to 6 months after the third injection. A significantly higher incidence of multiple recurrences was noted in patients who experienced their first recurrence less than 6 months after the third injection (13 of 16 eyes, 83.3%) compared with patients who had their first recurrence 6 or more months after the third injection (5 of 14 eyes, 35.7%) (P = 0.011). Recurrence did not occur in 23.8% of the patients with Type 3 neovascularization who were initially treated with 3 monthly ranibizumab injections. Close follow-up examination may be needed 4 months to 6 months after the third ranibizumab injection. The close follow-up or continuous injection may also be required for patients with early first recurrences.

ARMS2 A69S polymorphism is associated with the number of ranibizumab injections needed for exudative age-related macular degeneration in a pro re nata regimen during 4 years of follow-up.

To investigate whether single-nucleotide polymorphisms (SNPs) known to be strongly associated with the development of age-related macular degeneration (AMD) have an influence on recurrence rate of choroidal neovascularization (CNV) activity during 4-year ranibizumab treatment for exudative AMD. This prospective study included 103 treatment-naïve patients (103 eyes) that received initially a loading dose of 3 monthly ranibizumab injections and thereafter, were treated according to an as-needed regimen for a 4-year follow-up period. Baseline values, visual outcome, and recurrence rate were examined. CFH Y402H and ARMS2 A69S polymorphisms were determined and their association with lesion recurrence and visual outcome was analyzed using a one-way analysis of variance (ANOVA) with post hoc comparison tested by Fisher's LSD method. Multivariate linear regression analysis was then used to identify factors associated with recurrence rate. The cumulative total mean number of ranibizumab injections at the end of each year of the follow-up was 5.3±1.8, 9.2±2.9, 12.6±4.6, and 15.7±6.1. There was great inter-patient variability. Nineteen eyes (18.5%) did not experience recurrence during the first year, and five (4.8%) still displayed inactive CNV after 4years of follow-up. No significant association was found between the number of injections and mean best corrected visual acuity (BCVA) change or final BCVA at the end of the study period. Genotypes had no influence on baseline characteristics or visual outcome but a significant association was found between the A69S polymorphism and the number of injections needed by the patients. Homozygous for the T risk allele required more retreatments over the 48-month follow-up. The ARMS2 A69S polymorphism was associated with CNV recurrence rate in our patient cohort. Prediction of a greater risk of recurrence could help to design more appropriate follow-up treatment strategies for patients with neovascular AMD.

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.

Retinal Pigment Epithelium Tear Following Aflibercept for Exudative Macular Degeneration Tachyphylactic to Anti-Vascular Endothelial Growth Factor A Agents

Purpose: To report two cases of retinal pigment epithelium (RPE) tears following treatment with aflibercept of exudative macula degeneration associated with pigment epithelial detachment (PED) tachyphylactic to antivascularendothelial growth factor (VEGF) A agents such as bevacizumab or ranibizumab.Methods: Retrospective case series of patients with exudative macular degeneration with PED who were managed with anti-VEGF A agents that developed RPE tear following the first aflibercept injection. The patients were followed with optical coherence tomography and fluorescein angiography.Results: In our two cases, RPE tear developed after being switched from bevacizumab or ranibizumab to treatment with aflibercept. Both cases were rescued with monthly ranibizumab injections. In each case vision and macular edema improved with continued treatment.Conclusion: RPE tears may occur following injection with aflibercept for treatment of exudative AMD tachyphylactic to bevacizumab or ranibizumab. Continued anti-VEGF treatment can be effective rescue therapy.

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.

Long-Term Outcomes in Patients with Neovascular Age-Related Macular Degeneration Who Maintain Dry Macula after Three Monthly Ranibizumab Injections

ABSTRACTPurpose: To evaluate long-term changes in visual acuity and retinal microstructure in patients with neovascular age-related macular degeneration (AMD) who had maintained dry macula after initial treatment. Methods: This retrospective observational study included 55 eyes that were diagnosed with neovascular AMD, were treated with three monthly ranibizumab injections, and maintained dry macula during a two-year follow-up. Best-corrected visual acuity (BCVA) at three months and at the final follow-up were compared, and the degree of visual improvement was compared between eyes with and without improvement of the ellipsoid zone. In addition, the incidence of improvement of the ellipsoid zone was compared between eyes with different extents of disruption. Results: The mean follow-up period was 30.3 ± 4.1 months. BCVA at three months and at the final follow-up was 0.51 ± 0.46 and 0.45 ± 0.49 (P<0.001). Among 35 eyes that exhibited >200 μm of disruption of the ellipsoid zone, 15 (42.9%) showed improvement of the ellipsoid zone, and the improvement in BCVA was greater in these eyes than that in the remaining 20 eyes (P=0.021). A higher incidence of improvement of the ellipsoid zone was noted in eyes with 200 to 800 μm of disruption than in eyes with >800 μm of disruption (P<0.001). Conclusions: Long-term improvement in visual acuity was noted in eyes that had maintained dry macula after three ranibizumab injections. The status of the ellipsoid zone at three months was closely associated with visual improvement.

High-frequency aflibercept injections in persistent neovascular age-related macular degeneration.

To report the 1-year outcomes of every-4-weeks (Q4W) as-needed aflibercept treatment in resistant neovascular age-related macular degeneration (nAMD) patients who had been treated and failed prior bevacizumab or ranibizumab injections, and who also responded poorly to every-8-weeks (Q8W) aflibercept treatment. Forty-three eyes of 39 patients with persistent nAMD despite monthly bevacizumab and/or ranibizumab injections and who were switched to Q8W 2-mg aflibercept injections, but showed persistence of fluid were included. Patients were treated with as-needed Q4W aflibercept injections with monthly monitoring. Maximum retinal thickness (MRT), central macular thickness (CMT), maximum pigment epithelial detachment height (PED) and best-corrected visual acuity (BCVA) were assessed and compared to baseline when high-frequency aflibercept was initiated. A mean of 8 (interquartile range, 4-11) Q4W injections were given during the follow-up. MRT and CMT significantly decreased at all follow-up visits (p < 0.05); however, there was no significant change in maximum PED height (p > 0.05) at any visit. Mean BCVA was 0.38 ± 0.28 (logMAR) (≈20/63, Snellen) at baseline, and 0.4 ± 0.34 (logMAR) (≈20/76, Snellen) at 1 year (p = 0.76). Seventy-two percent of eyes maintained a final BCVA of 20/63 or better. Twelve eyes (28%) had some subretinal scar tissue formation and 5 eyes (11.6%) had evidence of atrophy at 1 year. A stepwise algorithm with Q4W as-needed aflibercept treatment led to anatomic improvement in previously treated eyes which failed other therapies, including aflibercept every 8weeks. Lack of visual improvement may be due to a ceiling effect as our eyes generally had good visual acuity.

Randomized Trial of Treat and Extend Ranibizumab with and without Navigated Laser for Diabetic Macular Edema: TREX-DME 1 Year Outcomes

To compare monthly dosing with a treat and extend algorithm using ranibizumab 0.3 mg with and without angiography-guided macular laser photocoagulation for center-involving diabetic macular edema (DME). Multicenter, prospective, randomized clinical trial. A total of 150 eyes from 116 subjects were randomized into 3 cohorts: Monthly (n= 30), TReat and EXtend without macular laser photocoagulation (TREX; n= 60), and treat and extend with angiography-GuIded macular LAser photocoagulation (GILA; n= 60). Monthly cohort eyes received ranibizumab 0.3 mg every 4 weeks. Eyes in the TREX and GILA cohorts received 4 monthly injections of ranibizumab 0.3 mg followed by a treat and extend algorithm based on disease activity. Eyes in the GILA cohort also received angiography-guided macular laser photocoagulation at month 1 and again every 3 months for microaneurysm leakage. Change in mean best-corrected visual acuity (BCVA), mean central retinal thickness (CRT), number of injections from baseline to 1 year, and percentage gaining/losing 2 and 3 lines of vision. Baseline demographics were well balanced among the cohorts. A total of 137 eyes (91%) completed the 1-year end point visit. At 1 year, the mean BCVA improved by 8.6, 9.6, and 9.5 letters in the Monthly, TREX, and GILA cohorts, respectively (P= 0.8). There was no significant difference between the cohorts in the percentage gaining/losing 2 and 3 lines of vision. The CRT improved by 123 μm, 146 μm, and 166 μm in theMonthly, TREX, and GILA cohorts, respectively (P= 0.47). The mean number of macular laser treatments in theGILA cohort at 1 year was 2.9 (range, 1-4). The number of injections was significantly reduced in both the TREX (10.7) and GILA (10.1) cohorts compared with the Monthly cohort (13.1, P < 0.001). There were no cases of endophthalmitis, and the total incidence of Anti-Platelet Trialists' Collaboration events was 4.7%. This prospective, randomized trial found that treat and extend dosing of ranibizumab 0.3 mg with and without angiography-guided macular laser photocoagulation significantly decreased the number of injections given while providing similar visual and anatomic outcomes compared with monthly dosing at 1 year. Adding angiography-guided laser photocoagulation to this dosing algorithm did not significantly improve outcomes at 1 year.

Worsening anatomic outcomes following aflibercept for neovascular age-related macular degeneration in eyes previously well controlled with ranibizumab.

PurposeAntivascular endothelial growth factor injection is the mainstay of treating neovascular age-related macular degeneration (AMD). Previous studies have shown that switching treatment from ranibizumab to aflibercept led to an improvement in eyes with recalcitrant activity. Herein, we identify a unique subset of patients whose eyes with neovascular AMD were previously well controlled with ranibizumab injections were then worsened after being switched to aflibercept.MethodsThis is a retrospective interventional case series. Eyes with neovascular AMD, previously well controlled with monthly injections of ranibizumab, which then developed worsening of subretinal fluid after being switched to aflibercept were included.ResultsA total of 17 eyes were included. All eyes developed increased subretinal fluid when switched from ranibizumab to aflibercept. Fourteen patients were switched back to ranibizumab after a single injection of aflibercept and had subsequent rapid resolution of subretinal fluid. Three patients continued with monthly aflibercept injections for two subsequent months and demonstrated the persistence of the increased subretinal fluid until they were switched back to treatment with ranibizumab at which time the fluid resolved. No eye had persistent decline in visual acuity.ConclusionSwitching from intravitreal ranibizumab to aflibercept in eyes with well-controlled neovascular AMD may result in worsening in a subset of patients and resolves when therapy is switched back to ranibizumab.

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.

Individualized Stabilization Criteria–Driven Ranibizumab versus Laser in Branch Retinal Vein Occlusion: Six-Month Results of BRIGHTER

To compare the 6-month efficacy and safety profile of an individualized stabilization criteria-driven pro re nata (PRN) regimen of ranibizumab 0.5 mg with or without laser versus laser alone in patients with visual impairment due to macular edema secondary to branch retinal vein occlusion (BRVO). A 24-month, prospective, open-label, randomized, active-controlled, multicenter, phase IIIb study. A total of 455 patients. Eligible patients were randomized 2:2:1 to receive ranibizumab (n= 183), ranibizumab with laser (n= 180), or laser only (n= 92). Patients treated with ranibizumab with or without laser received a minimum of 3 initial monthly ranibizumab injections until visual acuity (VA) stabilization, and VA-based PRN dosing thereafter. In the ranibizumab with laser and laser-only groups, laser was given at the investigator's discretion at a minimum interval of 4 months and if VA was <79 letters. Mean change from baseline at month 6 in best-corrected visual acuity (BCVA) (primary end point) and central subfield thickness, and safety over 6 months. Exploratory objectives were to evaluate the influence of baseline BCVA, disease duration, and ischemia on BCVA outcomes at month6. Baseline mean BCVA was 57.7 letters, and mean BRVO duration was 9.9 months. Ranibizumab with or without laser was superior to laser only in improving mean BCVA from baseline at month 6 (14.8 and 14.8 vs. 6.0 letters; both P < 0.0001; primary end point met). Patients with a shorter BRVO duration at baseline had a higher mean BCVA gain than those with a longer BRVO duration. Patients with a poor baseline VA had a better BCVA gain than those with a higher baseline VA, although final BCVA was lower in those with poor baseline VA. In the ranibizumab with or without laser groups, the presence of some macular ischemia at baseline did not influence mean BCVA gains. There were no new ocular or nonocular safety events. Ranibizumab with an individualized VA-based regimen, with or without laser, showed statistically significant superior improvement in BCVA compared with laser alone in patients with BRVO. Overall, there were no new safety events other than those reported in previous studies.

Comparison of intravitreal aflibercept and ranibizumab injections on subfoveal and peripapillary choroidal thickness in eyes with neovascular age-related macular degeneration.

We aimed to compare changes in subfoveal and peripapillary choroidal thickness (CT) after intravitreal aflibercept or ranibizumab injections for neovascular age-related macular degeneration (AMD). Medical records of 54 treatment-naïve, consecutive patients (54 eyes) who were diagnosed with neovascular AMD and received three monthly injections of aflibercept (21 eyes) or ranibizumab (33 eyes) were reviewed. Subfoveal and peripapillary CT were measured with images obtained using spectral domain optical coherence tomography at baseline and at three months. Subfoveal CT decreased from 232.2 ± 94.4μm at baseline to 207.1 ± 89.3μm at three months in the aflibercept group (p < 0.001) and from 231.5 ± 102.9μm to 220.0 ± 98.0μm in the ranibizumab group (p = 0.006). The reduction was greater in the aflibercept group than in the ranibizumab group (p = 0.024). Peripapillary CT decreased from 157.2 ± 62.2μm at baseline to 147.4 ± 62.2μm at three months in the aflibercept group (p < 0.001). However, the change in peripapillary CT from 154.9 ± 46.5μm at baseline to 152.3 ± 50.0μm at three months was not significant in the ranibizumab group (p = 0.123). Intravitreally injected aflibercept significantly decreased subfoveal CT more than ranibizumab. Choroidal thinning after aflibercept injection was not limited to the subfoveal area, but extended beyond the macula as well.

Anti-VEGF in a Marathon Runner’s Retinopathy Case

Central retinal vein occlusion (CRVO) is one of the most common retinal vascular disorders. Intense exercise associated CRVO have been described in otherwise healthy young patients. We describe a case of a young male ultramarathoner who presented with a CRVO, presumably associated with dehydration, making part of a marathon runner's retinopathy. Resolution of macular edema and subretinal fluid, with visual acuity improvement, was observed after 3 monthly injections of ranibizumab. Our case suggests that dehydration could be involved in the mechanism of CRVO in healthy young patients and ranibizumab may be an effective treatment option for marathon runner's retinopathy.

Alternating Bi-Weekly Intravitreal Ranibizumab and Bevacizumab for Refractory Neovascular Age-Related Macular Degeneration with Pigment Epithelial Detachment

Objective: To describe visual and anatomical outcomes following bi-weekly intravitreal ranibizumab/bevacizumab injections in eyes with refractory neovascular age-related macular degeneration (AMD) and pigment epithelial detachment (PED). Design: Retrospective, consecutive, interventional case series. Participants: Eighteen patients diagnosed with neovascular AMD that were refractory to anti-VEGF therapy and received alternating biweekly ranibizumab/bevacizumab injections were included. Methods: Patients with neovascular AMD and PED that were refractory to at least 11 monthly ranibizumab or bevacizumab injections were included in this study at a large, single retina practice. Following inclusion, patients received four bi-weekly alternating ranibizumab/bevacizumab intravitreal injections. After completing a course of four bi-weekly injections, patients were treated with variable regimens of intravitreal anti-vascular endothelial growth factor (VEGF) therapy. The primary outcomes of the study included change in visual acuity (VA) and central foveal thickness (CFT) at eight weeks follow-up. Results: Study eyes had previously received a mean of 22 intravitreal anti-VEGF injections. At enrollment, mean VA was 20/95 and mean CFT was 455 µm. After four bi-weekly anti-VEGF injections, mean VA improved to 20/65 (p < 0.001), and mean CFT decreased to 387 µm (p = 0.029). In patients with PED, there was a mean 27.9% reduction in height (p = 0.046) at eight weeks’ follow-up. Conclusions: Four injections of bi-weekly alternating ranibizumab/bevacizumab improved visual acuity and reduced macular thickness in a number of patients with refractory neovascular AMD and PED.

Factors Associated with Recurrence of Age-Related Macular Degeneration after Anti-Vascular Endothelial Growth Factor Treatment: A Retrospective Cohort Study

To investigate the predictive factors associated with recurrence after anti-vascular endothelial growth factor (VEGF) treatment for neovascular age-related macular degeneration (AMD). Retrospective cohort study. A total of 343 eyes of 326 patients with subfoveal neovascular AMD who were treated with an as-needed regimen after 3 monthly loading doses of intravitreal ranibizumab. Patients were followed up by an as-needed regimen for more than 1 year after the first injection. Baseline data and CFH I62V and ARMS2 A69S polymorphisms were analyzed for their association with recurrence after anti-VEGF treatment. Regression analysis was used to identify independent predictors of visual acuity (VA) prognosis. The primary end point was the presence or absence of recurrence. The secondary end point was VA improvement. In total, 236 eyes (68.8%) showed complete resolution of retinal exudative change after the 3 loading injections, and 81 eyes (34.3%) experienced no recurrence during the first year. Of the 236 eyes, 139 (58.9%) were followed for more than 2 years and 35 (25.2%) showed no recurrent retinal exudation during 24 months. Visual acuity improvement was significantly better in eyes without recurrence than in eyes with recurrence during the 2-year period. Baseline characteristics and genotypes had no influence on response to ranibizumab loading treatment. Stepwise analysis revealed that age (P<0.001), subtype of AMD (P=0.041), and VA at baseline (P<0.001) were associated with VA at 24 months. Older patients (P=0.006) and male patients (P=0.018) tended to require re-treatment for recurrence during the first year, yet the statistical significance disappeared when evaluated in 2 years. The subtypes of neovascular AMD were solely associated with the interval to the recurrence, which was shorter in eyes with polypoidal choroidal vasculopathy (PCV) than in eyes with typical AMD (P=0.015). Older age and male sex may predict recurrence after 3 monthly ranibizumab injections, and PCV may be associated with shorter interval to recurrence. Predicting the risk of recurrence would help us to choose the most appropriate follow-up treatment strategy for patients with AMD.

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.

REFRACTORY INTRARETINAL OR SUBRETINAL FLUID IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION TREATED WITH INTRAVITREAL RANIZUBIMAB: Functional and Structural Outcome.

To investigate the visual acuity results of eyes with neovascular age-related macular degeneration and refractory fluid despite monthly treatment with ranibizumab, and to investigate differences between refractory subretinal fluid and intraretinal cystic changes. Retrospective chart review of consecutive treatment-refractory neovascular age-related macular degeneration, defined as persistent intraretinal or subretinal fluid despite monthly ranibizumab injections during 12 months or more. Data were evaluated for baseline characteristics, type and location of the refractory fluid, mean visual acuity change, number of injections, and the time point of first complete disappearance of all fluid on spectral domain optical coherence tomography. Seventy-six eyes (74 patients, mean age, 76.8 years) were identified. The mean follow-up was 33.6 months (range, 12-73 months). The mean number of injections was 11.4 in the first year and 27.7 over follow-up. The refractory fluid was located subfoveally in 61.8%. In 27 eyes (35.5%), the fluid resolved after a mean of 21.8 months (range, 13-49 months). Mean visual acuity increased by 9.0, 7.9, and 7.9 letters by Month 12, Month 24, and Month 36, respectively. Subgroup analysis revealed a higher risk for fibrosis (odds ratio, 3.30) or atrophy (odds ratio, 3.34) in patients with refractory cysts as compared with refractory subretinal fluid. Furthermore, refractory cysts showed a higher risk for a 10-letter visual acuity loss (P = 0.018). Fluid refractory to monthly treatment with ranibizumab for neovascular age-related macular degeneration still allowed for well-maintained visual improvement, even in subfoveal location. Late fluid resolution may occur. However, refractory cysts were associated with poorer anatomical and functional outcome than subretinal fluid.

Changes of choroidal neovascularization in indocyanine green angiography after intravitreal ranibizumab injection.

To investigate vascular structural changes of choroidal neovascularization (CNV) followed by intravitreal ranibizumab injections using indocyanine green angiography. A total of 31 patients with exudative age-related macular degeneration and CNV whose structures were identifiable in indocyanine green angiography were included. Ranibizumab was injected into the vitreous cavity once a month for 3 months and then as needed for the next 3 months prospectively. Indocyanine green angiography was performed at baseline, 3, and 6 months. Early to midphase images of the indocyanine green angiography in the details of vascular structure of the CNV were discerned the best were used in the image analysis. Vascular structures of CNV were described as arteriovenular and capillary components, and structural changes were assessed. Arteriovenular components were observed in 29 eyes (94%). Regression of the capillary components was observed in most cases. Although regression of arteriovenular component was noted in 14 eyes (48%), complete resolution was not observed. The eyes were categorized into 3 groups according to CNV structural changes: the regressed (Group R, 10 eyes, 31%), the matured (Group M, 7 eyes, 23%), and the growing (Group G, 14 eyes, 45%). In Group R, there was no regrowth of CNV found at 6 months. In Group M, distinct vascular structures were observed at 3 months and persisted without apparent changes at 6 months. In Group G, growth or reperfusion of capillary components from the persisting arteriovenular components was noted at 6 months. Both capillary and arteriovenular components were regressed during monthly ranibizumab injections. However, CNV regrowth was observed in a group of patients during the as-needed treatment phase.

Parafoveal contributions to retinal function during ranibizumab therapy for age-related macular degeneration

ObjectiveThe standard measure for the assessment of functional vision in the central retina is best corrected visual acuity (VA). Our aim was to investigate whether it is an advantage to include tests for functional changes in the near retinal periphery to monitor treatment effects in patients receiving multiple injections of anti–vascular endothelial growth factor (anti-VEGF) agents for advanced exudative age-related macular degeneration (AMD). DesignProspective pilot study. ParticipantsOur cohort consisted of 24 patients with exudative AMD (mean age ± SD: 77.46 ± 7.82 years) treated at an ophthalmology clinic. MethodsWe compared data from standard functional measurements, VA-near, and contrast sensitivity (CS), with results from the macular mapping test (MMT) at 10% and 100% contrast. Measurements of retinal thickness by optical coherence tomography (OCT) were used to document the morphologic efficacy of the anti-VEGF agent. Tests were performed at baseline and 4 weeks after 3 monthly ranibizumab injections. ResultsAll 4 functional tests yielded successes (equal or better visual performance after treatment) in 79.2% to 83.3% of cases. Including test locations in the near periphery yielded the highest success rate in the MMT at 10% contrast. Values for VA-near and CS also improved in a majority of cases. OCT measurements of retinal thickness indicated that the agent was effective in the fovea and near periphery. ConclusionsOur findings indicate that using the MMT adds information about functional changes in the near periphery of the retina and allows more sensitive assessment of treatment effects or disease progression without the high expense of other techniques.

Dexamethasone intravitreal implant as adjunct therapy for patients with wet age-related macular degeneration with incomplete response to ranibizumab

PurposeTo evaluate the visual and anatomical outcomes of dexamethasone intravitreal implant (DXI; 700 μg, Ozurdex; Allergan, Irvine, California, USA) as adjunctive therapy for patients with refractory wet age-related macular degeneration...