Pro Re Nata Research Articles

Sustained Benefits of Ranibizumab with or without Laser in Branch Retinal Vein Occlusion: 24-Month Results of the BRIGHTER Study

To evaluate the long-term (24-month) efficacy and safety of ranibizumab 0.5 mg administered pro re nata (PRN) with or without laser using an individualized visual acuity (VA) stabilization criteria in patients with visual impairment due to macular edema secondary to branch retinal vein occlusion (BRVO). Phase IIIb, open-label, randomized, active-controlled, 3-arm, multicenter study. A total of 455 patients. Patients were randomized (2:2:1) to ranibizumab 0.5 mg (n= 183), ranibizumab 0.5 mg with laser (n= 180), or laser (with optional ranibizumab 0.5 mg after month 6; n= 92). After initial 3 monthly injections, patients in the ranibizumab with or without laser arms received VA stabilization criteria-driven PRN treatment. Patients assigned to the laser arm received laser at the investigator's discretion. Mean (and mean average) change in best-corrected visual acuity (BCVA) and central subfield thickness (CSFT) from baseline to month 24, and safety over 24 months. A total of 380 patients (83.5%) completed the study. Ranibizumab with or without laser led to superior BCVA outcomes versus laser (monotherapy and combined with ranibizumab from month 6; 17.3/15.5 vs. 11.6 letters; P < 0.0001). Ranibizumab with laser was noninferior to ranibizumab monotherapy (mean average BCVA change: 15.4 vs. 15.0 letters; P < 0.0001). However, addition of laser did not reduce the number of ranibizumab injections (mean injections: 11.4 vs. 11.3; P= 0.4259). A greater reduction in CSFT was seen with ranibizumab with or without laser versus laser monotherapy over 24 months from baseline (ranibizumab monotherapy-224.7 μm, ranibizumab with laser-248.9 μm, laser [monotherapy and combined with ranibizumab from month 6]-197.5 μm). Presence of macular ischemia did not affect BCVA outcome or treatment frequency. There were no reports of neovascular glaucoma or iris neovascularization. No new safety signals were identified. The BRIGHTER study results confirmed the long-term efficacy and safety profile of PRN dosing driven by individualized VA stabilization criteria using ranibizumab 0.5 mg in patients with BRVO. Addition of laser did not lead to better functional outcomes or lower treatment need. The safety results were consistent with the well-established safety profile of ranibizumab.

Long-Term Follow-Up of Choroidal Neovascularization due to Angioid Streaks with pro re nata Intravitreal Anti-VEGF Treatment

Purpose: To evaluate the long-term outcomes of intravitreal anti-vascular endothelial growth factor (VEGF) drugs with a pro re nata (PRN) regimen for the treatment of choroidal neovascularization (CNV) secondary to angioid streaks (AS). Methods: This is a retrospective, multicenter, noncomparative case series of consecutive AS eyes affected by treatment-naïve CNV. A complete ophthalmologic examination was performed every 30-45 days after the loading phase, including fluorescein angiography and/or optical coherence tomography. Results: In all, 52 eyes of 39 patients were treated with intravitreal bevacizumab and/or ranibizumab and followed up for a mean of 33.8 months. The best corrected visual acuity at baseline was 20/40, and it deteriorated by an average of 6.8 ETDRS letters per year (p < 0.001). We performed an average of 5.1, 6.5, and 6.8 injections at the 1-, 2-, and 3-year follow-up, respectively. Conclusions: Intravitreal anti-VEGF drugs in a PRN regimen with close monitoring appear to slow the progression of CNV in AS, but they do not prevent the affected eyes from progressive visual loss.

Evaluation of Aflibercept Treatment Responses in Eyes with Bevacizumab/Ranibizumab-resistant Wet Age-related Macular Degeneration.

Objectives:To evaluate anatomic and functional results after switching from intravitreal bevacizumab or ranibizumab treatment to aflibercept for wet (neovascular) age-related macular degeneration.Materials and Methods:This retrospective study included 22 eyes of 22 patients resistant to treatment with at least 6 injections of bevacizumab or ranibizumab. The first three injections had been applied monthly, the others pro re nata (PRN). Outcome measures were follow-up period, injection number, best corrected visual acuity (BCVA), central retinal thickness (CRT) and pigment epithelial detachment (PED) height. Dosing regimen of aflibercept was determined PRN. The patients were examined monthly. In all visits, BCVA and optical coherence tomography results were assessed together and injections were applied according to these findings. Patients with at least three months of follow-up were included in the study.Results:Twenty-two eyes of 22 patients treated with bevacizumab or ranibizumab were switched to aflibercept therapy. Seven patients had serous PED and 4 patients had fibrovascular PED. The mean follow-up periods for these groups were 20.59±6.76 months and 8.68±3.79 months, respectively. The mean injection numbers were 10.5±3.61 vs 4.54±1.56. Statistically significant reductions were noted in CRT (533.86±164.06 µm vs 412.04±143.86 µm, p<0.05). BCVA levels were almost equal before and after switching (0.18±0.17 vs 0.18±0.14). Serous and fibrovascular PED heights decreased suboptimally from 460±281.51 µm to 282.42±175.76 µm (p>0.05) for serous PEDs and 251.25±43.85 µm to 225.75±73.09 µm (p>0.05) for fibrovascular PEDs.Conclusion:Switching to aflibercept resulted in significant improvement in CRT, but not in BCVA or PED heights.

Aflibercept in age-related macular degeneration: evaluating its role as a primary therapeutic option.

The recent VIEW studies have demonstrated the non-inferiority of monthly and bi-monthly aflibercept in the management of wet age related macular degeneration (AMD) compared with ranibizumab. However, the current data are limited mainly to fixed dosing regimens with few studies looking at flexible dosing regimens of aflibercept in wet AMD. In addition, recent data from the VIEW 96 week extension has shown that patients being shifted from fixed dosing regimens to PRN have shown a drop in visual acuity and increase in central macular thickness. This is an indication that fixed dosing, a non-sustainable option, is only effective as long as it is continued. Regimens such as treat and extend (TAE) and pro-re nata (PRN) have been studied extensively in ranibizumab and bevacizumab and have shown to be effective options. With the presence of effective, established and less costly drugs such as ranibizumab and bevacizumab, the role of aflibercept as a primary treatment modality has yet to be clearly defined. The current review provides an analysis of the VIEW studies, as well as the extension phases. It also looks at post hoc analysis of predictors of response and outcomes. We have also conducted a search on studies comparing between PRN regimens using aflibercept and other anti-VEGF agents. This review also explores cheaper off label aflibercept; ziv-aflibercept in the treatment of wet AMD. The main purpose of the review is to delineate the role of aflibercept as a primary therapeutic option and if there are any significant advantages that would advocate its use over alternative anti-VEGF drugs. Finally, we propose a treatment algorithm for patients being started on aflibercept during the first year and thereafter.

Relationship Between Visual Acuity and Retinal Thickness During Anti–Vascular Endothelial Growth Factor Therapy for Retinal Diseases

To investigate the relationship between best-corrected visual acuity (BCVA) and central retinal thickness (CRT) in eyes receiving ranibizumab for 3 common retinal diseases. Retrospective analysis of clinical trial data. Early Treatment Diabetic Retinopathy Study BCVA and spectral-domain optical coherence tomography-measured CRT of 387 eyes of 345 patients enrolled in 6 prospective clinical trials for management of neovascular age-related macular degeneration (AMD), diabetic macular edema (DME), and retinal vein occlusion (RVO) were evaluated by Pearson correlation and linear regression. At baseline, there was a small correlation between BCVA and CRT in pooled AMD trial data (r=-0.24). A medium correlation was identified in pooled DME trial data (r=-0.42). No correlation was found in pooled RVO trial data. At month 12, no correlation was found between changes from baseline in BCVA and CRT in pooled AMD trial data. Medium correlations were identified in both pooled DME (r=-0.45) and pooled RVO (r=-0.35) trial data at month 12. Changes in BCVA and CRT associated with edema recurrence upon transition from monthly to pro re nata (PRN) dosing were correlated in AMD (r=-0.27) and RVO (r=-0.72) trials, but not in DME trial data. DME demonstrated a convincing relationship between BCVA and CRT. Correlations appear to be more complex in AMD and RVO. At the inflection point between monthly and PRN dosing, when recurrence of edema is anticipated in many patients, CRT appears strongly correlated with loss of BCVA in RVO.

Resource Use and Real-World Outcomes for Ranibizumab Treat and Extend for Neovascular Age-Related Macular Degeneration in the UK: Interim Results from TERRA.

IntroductionRanibizumab is an inhibitor of vascular endothelial growth factor-A (anti-VEGF) approved for the treatment of neovascular age-related macular degeneration (nAMD). The treat and extend (T&E) regimen can potentially reduce the burden of clinic visits compared with a pro re nata (PRN) regimen. Retrospective, interim analyses of clinical effectiveness, treatment and resource use patterns were conducted using real-world data in England and Wales from the TERRA study.MethodsTwo cohorts, those switching from a PRN to a T&E regimen (‘prior PRN’) and those initiating ranibizumab on the T&E regimen as their first anti-VEGF therapy (‘anti-VEGF-naïve’) were enrolled in TERRA. Retrospective clinical assessments were gathered from medical records, while resource use patterns were collected via an operating cost questionnaire completed by each study site.ResultsAt the interim analysis cut-off date (15 November 2016), 11 sites had enrolled 145 patients (prior PRN: n = 110; anti-VEGF-naïve: n = 35). Mean change from baseline (date of first injection) in visual acuity and central subfield retinal thickness to 12 months was +7.6 Early Treatment Diabetic Retinopathy Study letters [95% confidence interval (CI) 2.8, 12.4; p = 0.003; n = 27] and −67.7 μm (95% CI −106.5, −28.9; p = 0.001, n = 29), respectively, in the anti-VEGF-naïve cohort. Most T&E clinics were run as one-stop services (same-day monitoring and injection), whereas 4/10 PRN clinics were run as two-stop services (monitoring and injection on different days). In general, one-stop clinics used less staff resources and were likely to be shorter in duration for healthcare providers than the cumulative time spent for two-stop clinics.ConclusionThis is the first real-world observational study conducted in England and Wales demonstrating the effectiveness of the ranibizumab T&E regimen in anti-VEGF-naïve patients. T&E is compatible with one-stop clinic services, which these real-world data suggest to be less resource intensive than two-stop clinic services, possibly providing a dosing regimen beneficial to both patients and resource burden in UK clinical practice. Funding: Novartis Pharmaceuticals UK Limited.Electronic supplementary materialThe online version of this article (doi:10.1007/s40123-017-0091-9) contains supplementary material, which is available to authorized users.

Comparison of Conbercept with Ranibizumab for the Treatment of Macular Edema Secondary to Branch Retinal Vein Occlusion

ABSTRACTPurpose: To confirm the therapeutic efficacy of conbercept for the treatment of macular edema (ME) secondary to branch retinal vein occlusion (BRVO).Methods: In this prospective, randomized, and comparative study, patients were randomized and divided into conbercept (n = 18) and ranibizumab (n = 17) groups. After an initial intravitreal injection of either conbercept or ranibizumab, a pro re nata (PRN) strategy was adopted based on loss of visual acuity (VA) or increase in central macular thickness (CMT).Results: All patients were followed for ≥6 months. Baseline best-corrected visual acuities (BCVAs) were 0.67 ± 0.37 and 0.511 ± 0.23 logMAR in the conbercept and ranibizumab groups, respectively (p = 0.087, t-test). Baseline CMTs were 512.5 ± 115.22 and 491.23 ± 114.72 µm in the conbercept and ranibizumab groups, respectively (p = 0.993, t-test). Significant improvements in BCVA and reduction of CMT were observed in both groups at each follow-up visit and compared to baseline values (p < 0.05, t-test). No significant differences in improvement of BCVA (p > 0.05, t-test) or reduction of CMT (p > 0.05, t-test) were noted in either group. Mean numbers of injections were 2.28 ± 0.96 and 2.65 ± 1.17 for the conbercept and ranibizumab groups, respectively (p = 0.478, t-test), with no statistically significant differences between the two groups.Conclusion: Intravitreal injection of conbercept is shown to be safe and effective for the treatment of ME secondary to BRVO, based on 6-month follow-up data.

Theory of Planned Behavior Constructs Associated with Nurses’ Pain Assessment and Pro Re Nata (PRN) Opioid Analgesic Administration: A Cross-sectional Study

Little theory-based research has been performed to better understand nurses' perceptions of pain management. Framed by the theory of planned behavior, the aims of the study were to describe nurses' beliefs (behavioral, normative, and control) about pain management for hospitalized elderly patients with postoperative pain; to present an item analysis for beliefs, attitudes, perceived norms, perceived behavioral control, intentions, and behaviors (measured in case study vignettes) for nurses (a) with different durations of nursing experience, (b) working in university, public health, and military hospitals, and (c) who either had or had not received pain management training in the past six months; and to compare differences in the constructs across these three groups. A comparative descriptive cross-sectional design was used with a convenience sample of 140 Thai nurses working in three Bangkok hospitals. Participants responded to pain assessment and management questionnaires. Most nurses expressed fairly strong beliefs about pain assessment and pro re nata (PRN) opioid analgesic administration. Nurses with more than 10 years of experience had the highest scores for attitudes toward pain assessment and perceptions of others’ expectations about PRN opioid analgesic administration. Responses of nurses working in different types of hospitals indicated significantly different pain assessment and PRN opioid analgesic administration behaviors. No significant differences were found for nurses who did and did not receive pain management training. The study highlighted the need for improved pain management education for nurses to enhance the quality of patient care.

Comparison of pro re nata versus Bimonthly Injection of Intravitreal Aflibercept for Typical Neovascular Age-Related Macular Degeneration

Purpose: The aim of this study was to clarify the 1-year outcomes of pro re nata (PRN) and bimonthly intravitreal injections of aflibercept (IVA) for typical neovascular age-related macular degeneration (tAMD) after the initial 3 monthly IVA. Methods: We conducted a prospective, interventional study. Fifty-eight treatment-naïve patients with tAMD were randomly assigned to the PRN (30 patients) or the bimonthly (28 patients) treatment group. Both groups initially received 3 monthly IVA. Visual acuity, central macular retinal thickness (CRT), and central choroidal thickness (CCT) were evaluated at 12 months. Subanalysis was performed to identify factors associated with the best-corrected visual acuity (BCVA). Results: BCVA was significantly improved only in the bimonthly group at 12 months. CRT and CCT were significantly decreased in both groups. Subanalysis showed that the only factor associated with BCVA improvement at 12 months was the existence of pigment epithelial detachment at baseline. Conclusions: BCVA showed significant improvement only in the bimonthly group but not in the PRN group at 12 months.

Relation between macular morphology and treatment frequency during twelve months with ranibizumab for diabetic macular edema.

PurposeTo investigate whether baseline optical coherence tomography (OCT) parameters can predict the treatment frequency of intravitreal ranibizumab (IVR) injections during the first year in patients with diabetic macular edema (DME) treated with pro re nata (PRN) IVR injections.MethodsWe retrospectively reviewed 68 eyes of 63 patients with center-involved DME who received IVR injections for 12 months or longer according to three monthly IVR injections followed by the PRN dosing. We measured the mean retinal thicknesses in the individual subfields of the Early Treatment Diabetic Retinopathy Study grid and evaluated the qualitative and quantitative parameters on OCT sectional images. We investigated the relationship between these OCT parameters at baseline and the number of IVR injections during the 12-month follow-up.ResultsThree loading doses were administered to 10 eyes; four to seven annualized IVR injections were administered to 34 eyes. The number of eyes that received IVR injections decreased gradually until month 6 and was almost constant from months 7 to 11. No relationships were seen between the treatment frequency and baseline systemic factors and the ophthalmic examination findings. Univariate analyses showed that the number of IVR injections during the first year was associated with the mean retinal thickness in the individual subfields and the transverse length of the disrupted external limiting membrane (ELM) and ellipsoid zone of the photoreceptors. Multivariate analysis showed a significant association with the thickness in the inferior subfield alone. The treatment frequency during the 12-month follow-up was not correlated with improved visual acuity but was associated with the decrease in the central subfield thickness and disrupted ELM.ConclusionThe retinal thickness in the inferior subfield predicts the treatment frequency during the first year in eyes with DME treated with PRN IVR injections.

RANIBIZUMAB FOR MACULAR EDEMA AFTER BRANCH RETINAL VEIN OCCLUSION: One Initial Injection Versus Three Monthly Injections.

To compare the 12-month-efficacy of 1 initial intravitreal ranibizumab injection (IVR) followed by pro re nata (PRN) dosing with that of three initial monthly IVR followed by PRN dosing in patients with macular edema (ME) after branch retinal vein occlusion. Prospective, interventional study. Of 81 eyes, 42 received 1 initial IVR injection (1+PRN group) and 39 eyes received 3 monthly IVRs (3+PRN). Pro re nata injections were performed when fovea exudative changes were evident. At Month 12, the visual acuity (VA) changes from baseline were -0.245 ± 0.227 and -0.287 ± 0.222, in the 1+PRN and 3+PRN groups, respectively; there were no significant difference between groups (P = 0.728). The stratified analysis showed that patients with better VA (baseline VA >20/40) had similar significant improvement in VA at Month 12 (P < 0.001) to that of those with poorer VA (≤20/40). Better VA at Month 12 was significantly associated with younger age, better baseline VA, and thinner baseline central foveal thickness (P = 0.003, < 0.001, and < 0.001, respectively). Mean total number of IVR injections in the 1+PRN and 3+PRN groups were 3.8 ± 1.8 and 4.6 ± 1.4, respectively (P = 0.060). In both groups, shorter durations to the first PRN injection were associated with greater total PRN injection number (1+PRN, P = 0.006; 3+PRN; group, P < 0.001). In IVR treatment for ME after branch retinal vein occlusion, 1+PRN and 3+PRN regimens achieved similar 12-month functional outcomes. Patients with shorter durations to initial PRN injection may require more PRN treatments.

PRN Medication Administration in a Geriatric Psychiatric Hospital: Chart Review and Nursing Perspective

ABSTRACTObjective: To improve patient care/outcome, an evaluation was conducted of nursing procedures and protocols for pro re nata (PRN) medications.Methods: A 14-day chart review was conducted for 27 patients with mood and thought disorders (MTD) and for 24 patients with organic disorders (OD) at a geriatric psychiatric hospital, and a questionnaire was completed by 20 nurses.Results: 377 PRNs were administered to patients in the MTD and OD units (240 and 137, respectively). The majority of PRNs were administered during the evening shifts on the MTD unit and during the day shifts on the OD unit. Chart notes indicated the behavior requiring PRN administration was not always specifically described and therapeutic interventions were not often attempted before PRN administration. Inconsistency between chart notes and medication record books was noted in the majority of cases. It was often not known whether the PRN was initiated by the staff, patient, or family. PRNs were reported to be not effective in the majority of cases.Conclusions: Documentation was suboptimal and effectiveness was poor.Clinical Implications: It would be worthwhile to train all staff in a patient-centered or ecopsychosocial (i.e., non-pharmacological) model of care, which would provide staff alternatives to PRNs. In that context, it would be important to implement standards of practice into geriatric psychiatry inpatient settings for PRN administration and documentation.

Nurses' attitudes towards the use of PRN psychotropic medications in acute and forensic mental health settings.

Many countries now have national mental health policies and guidelines to decrease or eliminate the use of seclusion and restraint yet the use of Pro Re Nata (PRN) medications has received less practice evaluation. This research aimed to identify mental health nurses' attitudes towards the use of PRN medications with mental health consumers. Participants were working in forensic mental health and non-forensic acute mental health settings. The "Attitudes towards PRN medication use survey" was used and data were collected online. Data were analysed using the Statistical Package Social Sciences, Version 22.0. Practice differences between forensic and other acute mental health settings were identified related to the use of PRN medications to manage symptoms from nicotine, alcohol and other drug withdrawal. Differences related to the useage of comfort rooms and conducting comprehensive assessments of consumers' psychiatric symptoms were also detected. Qualitative findings highlighted the need for increased accountability for the prescribing and administration of PRN medications along with more nursing education/training to use alternative first line interventions. Nurses administering PRN medications should be vigilant regarding the indications for this practice to ensure they are facilitating the consumer's recovery by reducing the use of all forms of potentially restrictive practices in the hospital setting. The reasons for using PRN medications and PRN administration rates must be continually monitored to avoid practices such as high dose antipsychotics use and antipsychotic polypharmacy to ensure the efficacy of the consumers' management plans on their health care outcomes.

Intravitreal aflibercept in neovascular age-related macular degeneration previously treated with ranibizumab.

To report the change in visual acuity and central macular thickness (CMT) following treatment with intravitreal aflibercept injections in patients with neovascular age-related macular degeneration (nAMD) with suboptimum response to ranibizumab. This was a retrospective study. The inclusion criteria were patients with nAMD who responded poorly to ranibizumab. Patients then received either 3 consecutive aflibercept injections followed by pro re nata (PRN) treatment or PRN alone. Primary endpoints were mean change in best-corrected visual acuity (BCVA) and CMT at 12mo. Secondary endpoints were number of injections and adverse events. Forty-nine eyes from 49 patients met the inclusion criteria and completed 12-month follow up on aflibercept. Thirty-eight eyes received 3 consecutive aflibercept injections followed by PRN treatment and 11 eyes received PRN injections alone. At 12mo, mean BCVA improved by one letters (logMAR 0.56±0.31 to 0.54±0.34) and mean CMT decreased from 303.9±82.1 to 259.2±108.3 µm. Four percent of eyes gained 15 letters or more, 6% lost more than 15 letters and the remaining 90% had stable BCVA. The mean number of aflibercept injections was 6. There was one case of infectious endophthalmitis. Intravitreal aflibercept in patients with nAMD with a previous suboptimal response to ranibizumab resulted in an anatomical improvement in macular appearance at 12mo without a corresponding improvement in visual acuity.

Head‐to‐head comparison of ranibizumab PRN versus single‐dose dexamethasone for branch retinal vein occlusion (COMRADE‐B)

To compare the efficacy and safety of ranibizumab 0.5mg versus dexamethasone 0.7mg according to their European labels in macular oedema secondary to branch retinal vein occlusion (BRVO) in a 6-month, phase IIIb, randomized trial. Patients received either monthly ranibizumab for 3months followed by Pro re nata (PRN) treatment (n=126) or a sustained-release dexamethasone implant followed by PRN sham injections (n=118). Main outcomes were mean average change in best-corrected visual acuity (BCVA) from baseline to month 1 through month 6, mean changes in BCVA and foveal centre point thickness (FCPT), and adverse events (AEs). There was no difference in BCVA gains between the treatments prior to month 3. Best-corrected visual acuity (BCVA) gain with dexamethasone declined thereafter. From month 3 to month 6, mean BCVA change from baseline was significantly higher with ranibizumab than with dexamethasone [raw means (standard deviation):+16.2 (±11) letters versus +9.3 (±10.1) letters]. At month 6, the difference in BCVA gains from baseline was +17.3 letters in the ranibizumab versus +9.2 letters in the dexamethasone group. Patients in the ranibizumab group received a mean of 2.94 loading injections and 1.74 PRN retreatment injections, while those in the dexamethasone group received a single loading injection. Elevated intraocular pressure (IOP) and AEs were more frequent with dexamethasone than ranibizumab treatment. Ranibizumab PRN resulted in greater visual acuity (VA) gains in macular oedema following BRVO compared with single-dose dexamethasone over a 6-month study period, observed from month 3, when administered according to their European label. In clinical practice, retreatment with dexamethasone may be required prior to this point.

Health-related quality of life, visual function and treatment satisfaction following intravitreal dexamethasone implant for diabetic macular edema.

PurposeThe aim of this study was to explore and describe quantitatively patient-reported outcome measures (PROMs), ie, health-related quality of life (QoL), visual function and treatment satisfaction, in patients with diabetic macular edema (DME) receiving two different regimens of Ozurdex (intravitreal dexamethasone implant).MethodsIn this multicenter, prospective study, 100 patients with center-involving refractory DME were randomized 1:1 to either five monthly fixed dosing or optical coherence tomography (OCT)-guided pro re nata (PRN) regimen of dexamethasone intravitreal implant therapy. The primary outcome was the difference between arms in change in PROMs and health-related QoL from baseline to 12 months, as measured by the Retinopathy-Dependent Quality of Life (RetDQoL) questionnaire, Visual Function Questionnaire-25 (VFQ-25) and Retinopathy Treatment Satisfaction Questionnaire (RetTSQ).ResultsThere was no statistically significant difference in the RetDQoL score and VFQ-25 score at month 12 compared to those at baseline, whereas the total mean RetTSQ score increased significantly at the exit visit. The two treatment arms did not differ significantly regarding the change in PROMs and health-related QoL questionnaires. Logistic regression analysis showed that visual acuity (VA) of ≥55 letters, central foveal thickness <300 μm and macular volume <9.2 mm3 at the exit visit (month 12) predicted a higher change in RetTSQ.ConclusionThis study showed that there is a statistically significant improvement in treatment satisfaction, as measured by RetTSQ, in patients with DME treated with dexamethasone intravitreal implant, independent of the dose regimen, namely, fixed or PRN. However, it should be noted that the clinically meaningful change could not be assessed accurately, since no thresholds for clinically meaningful change currently exist for the RetTSQ. On the other hand, there was no significant change in health-related QoL, as measured using VFQ-25 and RetDQoL. Factors affecting the patients’ treatment satisfaction were the final VA, the central foveal thickness and the macular volume.

Intravitreal Aflibercept for the Treatment of Subacute Central Serous Chorioretinopathy

Purpose: To evaluate the role of intravitreal aflibercept (IVA) for treating persistent central serous chorioretinopathy (CSCR) of more than 6 weeks. Methods: AFlibercept Efficacy in Cscr Treatment (NCT01971190) was a 6-month, phase 2, multicenter, prospective, randomized, controlled clinical trial at 6 clinical sites in Korea. Forty-three patients were randomized into group 1 (29) with 3 monthly IVA administrations or group 2 (14) with sham treatment and followed for 6 months with pro re nata (PRN) IVA. Patients could be retreated with IVA when they met the eligibility criteria for this. The primary end point was a mean change in central subfield thickness (CST) from baseline. Best-corrected visual acuity (BCVA) and CST were checked monthly. Data from a subgroup with long-term follow-up in a real-life practice were also compared. Results: After 3 months of treatment, group 1 had a greater change in mean CST (173.97 vs 80.15 µm; P = .001) and BCVA improvement (10.38 vs 8.62 Early Treatment of Diabetic Retinopathy Study letters; P = .52) than group 2. Among patients whose disease had lasted ≥3 months, BCVA improvement was significantly better in group 1 than in group 2 after 3 months (12.0 vs −2.7 letters; P = .007), and the percentage of eyes requiring PRN IVA was lower in group 1 (50% vs 100%). These differences were attenuated at 6 months but maintained during additional 6-month follow-up. Conclusion: Intravitreal aflibercept may facilitate the anatomical improvement in persistent CSCR and may improve the visual outcomes in relatively chronic cases. The IVA injection may be a therapeutic option for CSCR.

Functional impact of treatment with ranibizumab under a reactive strategy in patients with neovascular age-related macular degeneration

Abstract Objective To analyze the functional recovery using a pro re nata (PRN) dosing strategy with intravitreal injections of ranibizumab for patients with neovascular age-related macular degeneration (AMD). Material and methods An observational, retrospective, single-center study, was conducted on patients with neovascular AMD managed with a PRN strategy with ranibizumab, and were followed-up for a minimum of 18 months. Sociodemographic and clinical data were collected from medical records. The percentage of visual acuity (VA) recovered after losing 5 or more letters was calculated taking into account the previous visit, as well as considering the best VA recorded prior to the retreament. Results The analysis included 128 patients. The mean (SD) follow-up period was 18.9 (2.3) months. The mean (SD) elapsed days between onset of symptoms and diagnosis, and between prescription and administration of treatment was 50.2 (57.4) and 10.9 (16.0), respectively. Only 108 patients were prescribed ranibizumab after losing 5 or more letters of VA. The mean (SD) VA recovery compared to the previous VA was 70.3% (114.4). On the other hand, the mean (SD) VA recovery when considering the best VA registered before the retreatment was 43.5% (112.9), with 59.4% of re-treatments having a VA recovery below 75%, and with 11.7% not presenting any VA recovery. Conclusions A PRN dosing strategy with intravitreal ranibizumab for neovascular AMD may not be efficient in preserving and/or recovering VA in the long-term, due to a cumulative irreversible VA loss.

One-Year Outcomes of 1 + pro re nata versus 3 + pro re nata Intravitreal Aflibercept Injection for Neovascular Age-Related Macular Degeneration

Purpose: We compared 1-year outcomes of 1 + pro re nata (PRN) versus 3 + PRN of intravitreal aflibercept injection (IAI) for age-related macular degeneration (AMD). Methods: Forty-two eyes with naïve AMD received 3 + PRN IAI treatment and 47 eyes with naïve AMD received 1 + PRN IAI treatment. Visual acuity (VA), central retinal thickness (CRT), and central choroidal thickness (CCT) and number of administered IAIs during 12 months were compared. Results: VAs improved, and CRTs reduced significantly at any given month from baseline in both groups (p < 0.01, respectively). CCT reduced significantly at 3 months in the 3 + PRN group (p = 0.024) but not in the 1 + PRN group. The 1 + PRN group received fewer injections than the 3 + PRN group (p < 0.01). Conclusions: Aflibercept leads to equivalent VA and morphologic retinal improvement without administering 3 injections.

6-Year Results of CNV Secondary to Pathological Myopia Treated with Ranibizumab.

Background The current standard treatment of choroidal neovascularisation (CNV) secondary to pathological myopia (PM) is intravitreal injection of VEGF antagonists. We now present our 6-year results after treating patients with CNV secondary to PM with ranibizumab. Patients and Methods We retrospectively analysed 15 treatment-naive eyes of 13 patients (10 women, 3 men, mean age 59.2; standard deviation (SD) 11.1; range 41-78 years) with visual impairment related to CNV secondary to PM, who were treated with at least 1 injection of ranibizumab. Follow-up treatments were indicated according to our PRN (pro re nata) regimen. Re-treatment criteria were: reduction in visual acuity and/or activity in OCT or fluorescence angiography. Results Patients received a mean of 3.5 ranibizumab injections (SD 3.4; range 1-12) during a mean follow-up of 85 months (SD 6.6; range 76-102 months). Initial spherical equivalent was - 12.4 ± 4.0 dpt (range - 7.5 to 20.5 dpt). Baseline visual acuity was (log MAR) 0.65 ± 0.28. After one month, visual acuity improved to 0.43 ± 0.23 (p = 0.002), after 3 months to 0.38 ± 0.22 (p = 0.002), after 6 months to 0.34 ± 0.22 (p = 0.002) and after 9 months to 0.35 ± 0.23 (p = 0.002). After 1 year, visual acuity was 0.35 ± 0.24 (p = 0.001), after 2years 2 0.35 ± 0.23 (p = 0.001), after 3 years 0.35 ± 0.23 (p = 0.002), after 4 years 0.37 ± 0.23 (p = 0.002), after 5 years 0.38 ± 0.23 (p = 0.002), and after 6 years 0.39 ± 0.26 (p = 0.016). Conclusion After considerable initial improvement in visual acuity, the initial gain was maintained by a strict PRN regimen for the observation and treatment of patients with neovascular membranes secondary to pathological myopia. The number of injections needed to achieve stable visual acuity was lower than with other diseases that respond to anti-VEGF.