Pro Re Nata Group Research Articles

Outcomes of Pro Re Nata versus Treat-and-Extend Anti-VEGF Injections for Myopic Macular Neovascularization in Multiethnic Patients in the United States.

To compare visual outcomes and recurrence rates between pro re nata (PRN), treat-and-extend and stop (TES), and treat-and-extend with chronic maintenance dosing (TEM) regimens of anti-vascular endothelial growth factor (VEGF) injections for myopic macular neovascularization (MNV) in multiethnic patients. This retrospective study included patients treated with PRN, TES, or TEM for myopic MNV using intravitreal bevacizumab or ranibizumab. The primary outcome measure was visual improvement at 12 months. We included 127 eyes of 117 patients (75 females and 42 males). The mean follow-up duration was 37.9 months. We compared the outcomes of PRN (47 eyes [37%]), TES (52 eyes [41%]), and TEM (28 eyes [22%]). All groups showed significant visual improvement at 12 months and at the final follow-up (all P<0.05). Visual outcomes did not differ significantly between the three groups at 12 months and final follow-up (all P>0.05). However, the number of eyes with recurrences was significantly higher in the PRN group and significantly lower in the TEM group during follow-up (38%, 21%, and 11% in the PRN, TES, and TEM groups, respectively; P=0.020). The PRN group received the fewest injections during follow-up (5.3, 10.9, and 19.9 injections in the PRN, TES, and TEM groups respectively; P<0.001). Anti-VEGF injections with PRN, TES, or TEM regimens are effective for myopic MNV and have comparable visual outcomes. Since PRN provides favorable outcomes with fewer injections, it should be the first-line approach. However, a treat-and-extend approach with TES and TEM may be an option given individual patient factors.

Two different initial treatment regimens of Conbercept in diabetic macular edema: 12-month results from a multicenter randomized controlled study

BackgroundThe optimal treatment regimen for diabetic macular edema (DME) and predictors for its treatment`s outcome need emerging evidence but currently poorly studied. MethodsA prospective, multicenter, open label randomized controlled study among adult patients with DME was conducted. Eyes were randomized to three or six doses initial Conbercept treatments. Additional injections were suggested pro re nata (PRN) over 12 months. Optical coherence tomography angiography (OCTA) was adopted to quantify the macular vessel density. Visual acuity gain and anatomical improvement and their associated factors were evaluated by multivariable linear regression. Results41 patients with 59 eyes participated in current study. Patients in both 3 + PRN (n = 32 eyes) or 6 + PRN (n = 27 eyes) treatments experienced similar best-corrected visual acuity (BCVA) gain and anatomical improvement, including the central macular thickness, foveal avascular aone (FAZ) and the retinal vessel density. Over 12 months, eyes in the 6 + PRN group received better changes of the deep capillary plexus (2.53 ± 5.45%). In multivariate linear regression, the age significantly affected visual outcome in 3 + PRN group (β = -0.014, P = 0.028), while the initial CMT (β = -0.001, P = 0.022) and FAZ area (β = -0.946, P = 0.007) associated with visual outcome in 6 + PRN group. Furthermore, the duration of diabetes exhibited significant results on CMT among 3 + PRN group (β= -7.516, P = 0.04). ConclusionsBoth 3 + and 6 + initial treatment regimens of Conbercept loading dose achieved parallel anatomical and functional visual improvement, while 6 + group had a trend of better treatment outcome. Older age, higher initial CMT and longer duration of diabetes might influence the clinical outcomes over 12 months from baseline.

Efficacy and safety of different conbercept injection regimens in the treatment of choroidal neovascularization in pathological myopia: a retrospective study.

To investigate the clinical efficacy of conbercept 1 + pro re nata (PRN) (i.e., reinjection as needed after one injection) and 3 + PRN (reinjection as needed after 3months of injection) regimens in choroidal neovascularization secondary to pathological myopia (PM-CNV). From 06/2019 to 06/2020, 65 patients (65 eyes) confirmed with PM-CNV were included in this retrospective study. Intravitreal injection of 0.5mg conbercept was conducted either with the 1 + PRN or 3 + PRN strategy. Patients were followed up for 12months. The best-corrected visual acuity (BCVA), central retinal thickness (CRT), CNV lesion leakage area, the number of injections, and postoperative adverse reactions were observed. The mean age of the patients was 42.10 ± 4.69years, and the average diopter was -11.26 ± 2.97D. The BCVA at month 3 in the 3 + PRN (n = 30) group was lower than in the 1 + PRN (n = 35) group (P < 0.001). The CRT at month 3 in the 3 + PRN group was lower than in the 1 + PRN group (P < 0.001). After 12months, there were no differences in the BCVA and CRT between the two groups (P > 0.05). The number of injections was less in 1 + PRN than in 3 + PRN (2.14 ± 1.06 vs. 3.37 ± 0.76, P < 0.001) at 12months. No serious treatment-related ocular complications or serious systemic adverse events were found. The 1 + PRN and 3 + PRN strategies of intravitreal injection of conbercept are effective in treating PM-CNV. The 1 + PRN regimen required fewer injections, and it might be more suitable for the treatment of PM-CNV.

Efficacy of as-needed intravitreal injection compared to 3-monthly loading of anti-vascular endothelial growth factor agents for branch retinal vein occlusion

We investigated the efficacy of intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents in branch retinal vein occlusion (BRVO). Databases, including PubMed, EMBASE, and the Cochrane Library, were searched on November 11, 2022. Studies comparing the pro-re-nata (PRN) regimen after the first treatment (PRN group) to three consecutive monthly injection regimens followed by the PRN regimen (3 + PRN group) were investigated. The primary outcomes were the change in best-corrected visual acuity (BCVA) and the change in central retinal thickness (CRT), with the secondary outcome being the injection frequency. Among 195 reports on anti-VEGF treatment, six comparative studies were included in this meta-analysis. The two groups had no statistically significant differences in terms of BCVA or CRT. However, the total number of injections during follow-up was significantly lower in the PRN group than in the 3 + PRN group (95% CI − 2.09 to − 0.83). The as-needed injection regimen is as effective as 3-monthly loading in terms of anatomical and functional improvement for BRVO, along with a lower treatment burden for patients and physicians.

Three Monthly Injections Versus One Initial Injection of Ranibizumab for the Treatment of Macular Edema Secondary to Branch Retinal Vein Occlusion: 12-Month Results of a Prospective Randomized Study.

To compare three monthly injections versus one initial injection of intravitreal ranibizumab (IVR) followed by pro re nata (PRN) dosing to treat macular edema secondary to branch retinal vein occlusion (BRVO). Seventy-four patients were randomized (1:1) to the 3+ PRN or 1+ PRN groups. Patients underwent monthly evaluations and additional IVR injections were administered if the retreatment criteria were met. The functional and anatomical outcomes were recorded. The factors associated with the improvement in best-corrected visual acuity (BCVA) were analyzed. Sixty-nine patients (93.2%) completed the study. At 12months, the mean gain in BCVA was 12.9 letters in the 3 + PRN group and 14.3 letters in the 1 + PRN group, which was not significant (P = 0.59). The mean reduction in central macular thickness was 297.8μm in the 3 + PRN group and 300.2μm in the 1 + PRN group (P = 0.96). The macular vascular density changes of the superficial and deep capillary plexuses were not significantly different between the two groups (P = 0.99 and 0.70, respectively). The mean number of IVR injections was 5.0 in the 3 + PRN group and 4.2 in the 1 + PRN group (P = 0.17). The incidence of retinal neovascularization was similar in both groups (P = 0.67). The baseline BCVA, but not the treatment regimen, was significantly associated with the change in BCVA (P < 0.01). Significant gains in BCVA and maintenance of macular perfusion were achieved in BRVO eyes treated with the 3 + PRN or 1 + PRN regimens. Baseline BCVA was a prognostic factor for the visual improvement. A prospective randomized controlled trial to compare the 1 + PRN and 3 + PRN regimen in the treatment of macular edema secondary to branch retinal vein occlusion (ChiCTR2000038086).

Macular Sensitivity after Intravitreal Ranibizumab Injection for Macular Edema in Central Retinal Vein Occlusion: One versus Three Initial Monthly Injections

Background: We aimed to compare the macular sensitivity after one initial intravitreal injection of an anti-vascular endothelial growth factor (VEGF) agent followed by pro re nata (PRN) dosing with that after three initial monthly injections followed by PRN dosing in patients with central retinal vein occlusion (CRVO) and macular edema. Methods: We included 20 eyes of 20 patients with treatment-naïve macular edema in CRVO and followed them for 12 months after intravitreal ranibizumab injection (IRI). Before and 1, 3, 6, and 12 months after IRI, macular sensitivity within the central 1 mm, 3 mm, and 6 mm fields was measured with an MP3 microperimeter and best-corrected visual acuity (BCVA) was assessed. Eleven eyes received one initial IRI (1 + PRN group), and nine received three initial monthly IRIs (3 + PRN group). PRN injections were performed when fovea exudative changes were evident. Results: Mean macular sensitivity within the central 1 mm, 3 mm, and 6 mm fields significantly improved from baseline to month 12 in all treated eyes. We found no significant differences in macular sensitivity in the central 1 mm, 3 mm, or 6 mm fields between the two groups at month 1, 3, 6, or 12. The choice of treatment regimen (1 + PRN or 3 + PRN) showed no association with either macular sensitivity in the central 1 mm, 3 mm, and 6 mm fields or BCVA at month 12. Conclusions: These findings suggest that a 1 + PRN regimen improves macular sensitivity to a similar extent as a 3 + PRN regimen.

A Randomized, Controlled Trial of Treat-and-Extend vs. Pro Re Nata Regimen for Neovascular Age-Related Macular Degeneration.

PurposeTo compare the efficacy and safety of conbercept using a treat-and-extend (T&E) regimen vs. a pro re nata (PRN) regimen in Chinese patients with neovascular age-related macular degeneration (nAMD).MethodsThis was a randomized, multicenter, non-inferiority study. After an initial loading phase of three consecutive monthly intravitreal injections of 0.5 mg Conbercept, the patients were treated to PRN or T&E regimen. The prespecified retreatment criteria was defined as a more than 5-letter decrease in BCVA from the previous visit or any evidence of new retinal hemorrhages, or the presence of any IRF and any SRF of more than 200 μm in height at the sub-foveal center. The primary outcome was the mean change in best-corrected visual acuity (BCVA) from baseline to 24 months, with a prespecified non-inferiority limit of −5 letters.ResultsFrom July 2016 through August 2018, 141 participants were allocated and treated (T&E, n = 69; PRN, n = 72). About one fifth of the overall participants were dropped out during the 12-month follow-up (28/141, 19.9%), and about one thirds of the overall participants were lost during the 24-month follow-up (51/141, 36%). At 2 years, mean BCVA letter improvement was + 4.0 in the T&E group vs. + 5.1 in the PRN group, and T&E regimen was not non-inferior to PRN regimen [difference, −1.169 letters; 95% confidence interval (CI): −6.864 ∼ 4.526]. Subgroup analyses also demonstrate the similar results in PCV patients, naive patients and no-naive patients. The mean decrease in central subfield thickness were 180 ± 165 μm in the T&E group and 247 ± 230 μm in the PRN group, respectively. The patients in the PRN group had required significantly fewer injections than those in the T&E group (12.4 vs. 14.6 injections, P = 0.041). The types and rates of adverse events were comparable in the two treatment groups.ConclusionThese findings suggest that the T&E regimen was not non-inferior to the PRN regimen in patients with nAMD in terms of BCVA outcomes through 24 months.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT02802657.

Enhanced recovery after surgery multimodality pain regimen performs similar to PRN narcotics on outcomes and pain control after cardiac surgery: A quality improvement project.

While enhanced recovery after surgery (ERAS) pathways have been successfully applied for cardiac surgery, there has been limited research directly comparing ERAS protocols to ad hoc narcotic use after surgery. We hypothesized that a standardized ERAS protocol would provide similar pain management and psychoemotional outcomes while decreasing the use of opioids in the hospital and after discharge. As part of a 7-month quality improvement project, cardiac surgery patients on a fast-tracked to extubate pathway were assigned pro re nata (PRN) narcotic pain management for 3 months (n = 49). After a 1-month ERAS protocol optimization period, a separate group of patients were given the ERAS protocol (n = 34). Clinical outcomes were gathered, and participants completed a quality of recovery survey that allowed for the assessment of pain and symptom control at four-time points after surgery. Among 83 participants, 66% were male and the mean age was 53 years. There were no differences in patient characteristics between PRN and ERAS groups (all p > .244). There were no differences between ERAS and PRN groups for surgery characteristics (all p > .060), inpatient outcomes (all p > .658), or after-discharge outcomes (all p > .397). Furthermore, across all time-point comparisons, there were no supported differences in patient-reported outcome and pain control between the ERAS and PRN narcotic groups (all p > .075). An ERAS protocol demonstrated similar patient outcomes and pain control to traditional opioid use for postoperative cardiac surgery patients. Further research is recommended to further confirm the results of this study.

Treat-and-Extend vs. Pro Re Nata Regimen of Ranibizumab for Diabetic Macular Edema-A Two-Year Matched Comparative Study.

PurposeTo compare 2-year treatment outcomes of ranibizumab using treat-and-extend (T&E) or pro re nata (PRN) regimens for diabetic macular edema (DME) in clinical settings.MethodsWe retrospectively enrolled 34 patients (34 eyes) with DME treated with ranibizumab using the T&E regimen, and 34 patients (34 eyes) treated with ranibizumab using the PRN regimen and matched to cases in the treat-and-extend group by baseline best-corrected visual acuity (BCVA) and central foveal thickness (CFT). BCVA and CFT changes, number of injections and recurrence of macular edema over 2 years were compared between the groups.ResultsThe average BCVA gain in the T&E and PRN groups was 16.2 and 7.6 ETDRS letters at 2 years (p = 0.011), respectively. The mean CFT reduction was 145.5 ± 127.3 and 97.3 ± 152.5 μm in the T&E and PRN groups at 2 years (p = 0.035), respectively. The T&E group had a higher proportion of patients with BCVA gain ≥ 15 letters at months 18 (p = 0.015) and 24 (p = 0.029) than the PRN group. During the 2-year treatment periods, the T&E group received more injections than the PRN group (11.0 ± 3.2 vs. 6.2 ± 2.0; p < 0.001), while the PRN group had more recurrence of macular edema than the T&E group (71 vs. 41%; p = 0.015).ConclusionsAfter 2-year ranibizumab treatment for DME, better visual and anatomical improvement and less recurrence of macular edema were achieved in the T&E group, with more injections administered.

To investigate treat and extend versus pro re nata regimen in neovascular age-related macular degeneration: results from the IDEM study

The purpose of this study is to report the 24-month outcomes of a pro re nata (PRN) compared with a treat and extend (T&E) regimen in patients previously treated for neovascular age-related macular degeneration (nAMD). This was a 2-year prospective, single-center study. Previously treated patients for nAMD were randomized into two regimen groups: T&E and PRN groups. Main outcome measured was change in best corrected visual acuity (BCVA) from baseline to month 24. Secondary outcomes encompassed anatomical features such as central retinal thickness (CRT), number of intravitreal injections (IVI), and visits required. A total of 124 eyes received the T&E (n = 61) or PRN (n = 63) regimen. At month 24, the mean BCVA change was -4.4 early treatment diabetic retinopathy study (ETDRS) letters (T&E) and -3.4 ETDRS letters (PRN), with a difference of +1.1 ETDRS letters (95% CI [-2.25]; p = 0.006). The mean change in CRT was -10.6 µm (T&E) and -7.9 µm (PRN), with a difference of +2.6 µm (95% CI [+19.2]; p = 0.004). The T&E group had received a mean of +4.6 more injections (95% CI [-7.06; -2.12]; p < 0.001) at month 24. There was statistically proven non-inferiority between the PRN and T&E regimens in terms of visual and anatomical outcomes at 24 months, with significantly more IVI administered in the T&E regimen.

Preferred treatment regimen of aflibercept after treatment interruption in patients with neovascular age-related macular degeneration

BACKGROUND: The efficacy of antiangiogenic therapy in neovascular age-related macular degeneration depends on adherence to the intravitreal injection regimen and regular follow-up. In 2020, the COVID-19 pandemic and associated epidemiological restrictions in ophthalmological care delivery led to a massive lack of appropriate control and management of this condition.&#x0D; AIM: To determine the preferred regimen of intravitreal anti-VEGF therapy in patients with neovascular age-related macular degeneration who experienced treatment interruption due to the COVID-19 pandemic.&#x0D; MATERIAL AND METHODS: Thirty eyes of 26 patients (20 males and 6 females, mean age 73.7 10.4 years) with neovascular age-related macular degeneration were included; all of them experienced treatment interruption due to the COVID-19 pandemic during the second year of aflibercept therapy. Re-starting therapy, all patients were divided in two groups and received treatment as per the fixed dosing (bimonthly), or as pro re nata (PRN) regimen. All patients underwent standard ophthalmological examination and optical coherence tomography before and after treatment interruption as well as six months after treatment re-start.&#x0D; RESULTS: At six months after treatment re-start, best corrected visual acuity and central retinal thickness did not show statistically significant difference similar between the fixed dosing group and that of PRN dosing regimen (p = 0.34 and p = 0.85, respectively). However, patients of the fixed dosing group received for one more injection than those of the PRN group (median value 2.0 injections, 95% confidence interval 2.0-2.4; p = 0.0001). Preservation of the disease activity according to optical coherence tomography data, in the fixed regimen group was found in 10 eyes (71.4 %) versus 9 eyes (56.2 %) in the PRN group (p = 0.63).&#x0D; CONCLUSIONS: For neovascular age-related macular degeneration patients at the second year of treatment, an adequate therapeutic strategy for re-starting anti-VEGF therapy after treatment interruption appears to be the PRN regimen. PRN regimen allows reducing one injection in comparison to fixed dosing regimen with comparable functional outcomes during first 6 month.

One year outcomes of treat and extend and pro re nata (PRN) treatment regimens with aflibercept for polypoidal choroidal vasculopathy.

To compare the 1-year outcomes of treat-and-extend and pro re nata (PRN) treatment regimens with aflibercept for polypoidal choroidal vasculopathy (PCV), by the means of visual acuity (VA), frequency of recurrence of polypoidal lesions and developed fibrosis, and the number of intravitreal injections, and thus to determine which one is preferable in the maintenance phase in PCV. In our prospective study, only naive and previously untreated PCV patients were included. Initially one session of photodynamic therapy (PDT) and three monthly intravitreal injections of 2.0 mg aflibercept (IAIs) were applied in 38 eyes. After this loading phase, they were re-examined and 30 PCV eyes with no exudative phenomena were included in the study. They were divided in two groups; in the first one (16 patients) the PRN treatment modality of IAIs was applied, while in the second one (14 patients) the treat-and-extend regimen was applied. Over a 12-month period, VA significantly improved in treat-and-extend group (logMAR BCVA 0.41 ± 0.15 vs 0.57 ± 0.24 at baseline, p = 0.044), while in the PRN group VA remained stable (logMAR BCVA 0.70 ± 0.36 vs 0.65 ± 0.18 at baseline, p = 0.61). During the maintenance phase, the patients of treat-and-extend group did not encounter development/progression of fibrosis or any recurrent episodes, whereas the patients of PRN group had significantly more recurrent episodes (0 vs 1.37 ± 0.5, p < 0.001) and the frequency of development/progression of fibrosis was significantly higher (0% vs 44%, p = 0.02). However, the treat-and-extend treatment regimen was accompanied by significantly more administered IAIs (6 ± 0 vs 5.13 ± 1.08, p = 0.006). We highlighted the superiority of treat-and-extend regime with IAIs, which seems to yield better functional outcomes by preventing recurrence and subfoveal fibrosis, although a greater number of injections is required.

Comparison of Regularly Scheduled Ibuprofen Versus "Pro Re Nata" for Ankle Sprains in Children Treated in the Emergency Department: A Randomized Controlled Trial.

We compared pain and degree of disability in patients with acute ankle sprains receiving regular scheduled ibuprofen versus pro re nata (PRN). This study is a randomized single-blinded controlled trial of children aged 7 to 17 years presenting with acute ankle sprain to an emergency department. Patients were randomized to receive 10 mg/kg of ibuprofen per dose (maximum 600 mg) every 6 hours regular scheduled versus PRN. Outcome measures included a 100-mm visual analog scale pain and degree of disability at day 4. A sample size of 72 children had a power of 80% to detect a clinically meaningful difference of 20 mm between the regular and PRN group. We randomly assigned 99 patients to receive regular scheduled (n = 50) or PRN (n = 49) ibuprofen. Pain scores and degree of disability at day 4 showed no significant differences between groups. The rate of reported adverse effects was higher in the regular scheduled group (11.4% vs 9.5%) versus the PRN group. Our study suggests that there is little benefit from routinely using a regular scheduled ibuprofen regimen for acute pediatric ankle sprains.

Compliance and Visual Outcome Of “Treat-And-Extend” Versus “Pro Re Nata”Dosing of Intravitreal Bevacizumab in Wet Age-Related Macular Degeneration – A Perspective From a Developing Country

Introduction: Age- related Macular Degeneration (AMD) is the commonest cause of irreversible blindness and visual impairment in elderly, aged50 years or older contributing 8.7% of global blindness. Among the two types: “dry” and “wet”, the “wet” variant is treated using anti-VEGFs, mainly via two regimen – PRN or TREX.&#x0D; Objective: To study and compare the compliance, cost and visual outcome of “Treat-and- Extend (TREX)”versus “Pro Re Nata(PRN)” dosing of intravitrealbevacizumab in Wet AMD.&#x0D; Methodology: Sixty-four eyes of 64 patients with treatment naïve neovascular AMD were included and randomly divided into two groups, with each group comprising 32 eyes, by lottery system: “Group A [TREX]” and “Group B [PRN]”. Group A was treated with intravitrealbevacizumab [1.25mg/0.05ml] at presentation and at 1-month interval for 3 consecutive months [loading dose] and monthly till dry macula was obtained. Group B was treated with the same in “as needed” basis.Both Groups were followed up, for 1 year.&#x0D; Results Mean gain in visual acuity in the PRN group was 0.09 +/- 0.35 log MAR unit and in TREX, it was 0.14 +/- 0.3 log MAR unit within the period of 1 year.64% of the patients were compliant in TREX and 36% moderately complaint whereas in the PRN group, 24% were compliant, 60% moderately compliant and 16% noncompliant. Average hospital cost in PRN and TREX was NRs. 16, 170 (USD 149) and 23,785(USD 220) respectively.&#x0D; Conclusion: Compliance and visual outcome were better in TREX in comparison toPRN at 1 year of treatment with intravitrealbevacizumab for Wet AMD.

Macular Atrophy Incidence and Progression in Eyes with Neovascular Age-Related Macular Degeneration Treated with Vascular Endothelial Growth Factor Inhibitors Using a Treat-and-Extend or a Pro Re Nata Regimen: Four-Year Results of the MANEX Study

To compare the incidence and progression of macular atrophy (MA) in eyes with neovascular age-related macular degeneration (nAMD) treated with anti-vascular endothelial growth factor (VEGF) agents using either a treat-and-extend (T&E) or a pro re nata (PRN) regimen over 4 years in a real-world setting. Four-year, multicenter, retrospective comparative study. Two hundred sixty-four patients with treatment-naive nAMD. Consecutive patients with nAMD received anti-VEGF therapy according to a T&E (n= 163) or PRN (n= 101) regimen. Eyes were included if they had received anti-VEGF injections for a period of at least 4 years and had undergone annual fundus autofluorescence (FAF) and OCT imaging using Heidelberg Spectralis. Two masked graders independently delineated areas of MA from serial FAF images using Heidelberg region finder software, and growth rates were calculated. Incident MA was assessed using proportional hazard ratios. Macular atrophy incidence and progression over 4 years, association between treatment strategies, and number of injections. At baseline, MA was present in 24% and 20% of study eyes in T&E and PRN groups, respectively (P= 0.45). At year 4, 27% (34/124) and 25% (20/81) of eyes without baseline MA showed detectable MA in the T&E and PRN groups, respectively. In those with MA at baseline, the mean square root area of MA progressed by a rate of 0.4 ± 0.2 mm/year and 0.4 ± 0.1 mm/year in the T&E and PRN groups, respectively (P= 0.23). Multivariate analysis for baseline predictors of MA growth demonstrated that older age, poorer baseline visual acuity, and presence of retinal angiomatous proliferation had a higher risk of greater MA progression (P= 0.03). Regression analysis demonstrated no association between T&E and PRN treatment strategies with the risk of new MA developing during the 4 years of follow-up or the progression of pre-existing MA at year 4 (P= 0.692). Over 4 years, neither incidence nor progression of MA in eyes with nAMD treated with anti-VEGF injections was influenced by the treatment regimen and injection frequency. Eyes treated with a T&E regimen received more injections and achieved better visual outcomes compared with those treated with a PRN approach.

A Trinity regimen with aflibercept for treatment-naïve neovascular age-related macular degeneration: 2-year outcomes.

To evaluate the advantages of the Trinity regimen for treatment-naïve neovascular age-related macular degeneration (nAMD). Thirty-one treatment-naïve nAMD eyes were treated using the Trinity regimen with an intravitreal aflibercept injection (IVA) and evaluated after 24 months. Three treatment methods, pro re nata (PRN), treat and extend (TAE), and fixed regimen were changed depending on recurrence frequency. After the initial treatment, PRN or TAE (started for 4 or 8 weeks) was selected as per the recurrence interval. Subsequently, the recurrence interval became constant, transitioning from a TAE to fixed regimen. When the recurrence frequency became irregular, the treatment regimen was changed to TAE. After the initial treatment, 15 eyes (48.4%) were allocated to the PRN group, 12 (38.7%) to the TAE 8-week group, and 4 (12.9%) to the TAE 4-week group. Mean logMAR significantly improved in all cases, 0.53 ± 0.40 at baseline to 0.36 ± 0.34 at 24 months (p < 0.01), in the PRN group (0.63 ± 0.46 to 0.42 ± 0.43, p < 0.01), and the TAE 8-week group (0.44 ± 0.29 to 0.27 ± 0.19, p < 0.05). LogMAR in the TAE 4-week group was maintained. The mean number of injections for all and in the PRN, TAE 8-week, and TAE 4-week groups were 9.7, 5.3, 13.1, and 15.8, respectively, with the PRN group being significantly less (p < 0.01). The Trinity regimen delivered the benefits of the PRN, TAE, and FIXED regimens while minimizing injections during the early treatment phase without visual loss. This trial was registered with the University Hospital Medical Information Network (UMIN ID: 000038335).

Clinical outcomes of 1\u2009+\u2009PRN and 3\u2009+\u2009Q3M regimens of intravitreal conbercept injection for exudative age-related macular degeneration

This retrospective study aimed to analyze the clinical outcomes of two regimens of intravitreal injections of conbercept [1+pro re nata (PRN) and 3 + Q3M] for the therapy of exudative age-related macular degeneration (AMD). In total, 105 eyes diagnosed with exudative AMD were enrolled. The eyes in the 1+PRN group (n = 51) received intravitreal injection of conbercept one time, followed by PRN retreatment. The eyes in the 3 + Q3M group (n = 54) received intravitreal injection of conbercept on three consecutive monthly, subsequently, once every three months for three times. After treatment, patients were followed up for 12 months. The best-corrected visual acuity (BCVA), central retinal thickness (CRT), and choroidal neovascularization (CNV) leakage area were compared before and after treatment. Moreover, the number of injections and adverse reactions were recorded. Compared with the 1+PRN group, BCVA was significantly improved and CRT was remarkably decreased in the 3 + Q3M group at 3, 6 and 12 months after operation. The disappeared or reduced CNV leakage area (93%) of the 3 + Q3M group was higher than that of the 1 + PRN group at the last follow-up. Moreover, the mean numbers of conbercept injections of the 1 + PRN group were less than the 3 + Q3M group. During the follow-up, there were no serious adverse reactions or ocular complications. This study reveals that intravitreal injection of conbercept using 3 + Q3M regimen has certain advantages than 1 + PRN regimen in extending drug delivery interval, improving patient’s vision, and reducing CRT.

Efectividad de los regímenes tratar y extender vs. pro re nata para el tratamiento de degeneración macular neovascular vinculada a la edad: una comparación en un entorno real

PurposeEvaluate and compare the visual and morphological results of Pro re nata (PRN) and treat-and-extend (T&E) treatment regimens at 3 years in real world clinical practice. MethodsRetrospective study of patients with neovascular age macular degeneration (AMD) treated with anti-VEGF with 3 years of continuous follow-up and no previous anti-VEGF treatment. Best corrected visual acuity (BCVA), central foveal thickness (CFT) and number of intravitreal injections outcomes were tested for statistical differences between the two groups at baseline and during follow-up. ResultsA total of 240 eyes were included in the study, 170 in the PRN group and 70 in the T&E group. At 12 months, mean BCVA (ETDRS letters) gain from baseline was at its highest point in the T&E group (+6.38±13.32; p=0.25). In the PRN group, BCVA peaked at 3 months and slowly decreased until end of follow-up. With both regimens, from baseline, CFT continued to decrease until the second year (PRN -138.81 [-846.7 to +162.77] and T&E -81 [-604 to +100] μm, p=0.06). After that, T&E group maintained this tendency, reaching the lowest CFT value at 36 months, whereas PRN group showed an increased in CFT values (PRN -104 [-807.7 to +297] μm and T&E -103 [-575 to +244], μm p=0.63). Patients treated with T&E regimen received a significantly higher number of injections (PRN 16.3±7.6 vs T&E 23.9 ±9.4, p<0.01). ConclusionOur results demonstrated a trend towards for T&E to achieve higher marks in BCVA, peaking at 12 months, and lower CFT thickness at the end of three years. Despite the higher number of injections performed in the T&E group the mean BCVA reverts to baseline values at 3 years.

Different conbercept injection strategies for the treatment of exudative age-related macular degeneration: A retrospective cohort study.

Conbercept is a novel anti-vascular endothelial growth factor for the treatment of age-related macular degeneration (AMD). The most optimal injection strategy is unknown. To assess the effectiveness of intravitreal injection of conbercept using the 3 + pro re nata (PRN) and 3 + Q3 M strategies for the treatment of exudative AMD.From January 2015 to January 2018, patients confirmed with exudative AMD at Qilu Hospital of Shandong University were included in this retrospective study. Intravitreal injection of 0.5 mg of conbercept was conducted either with the 3 + PRN or 3 + Q3 M strategy. Best-corrected visual acuity (BCVA), intraocular pressure, and optical coherence tomography were conducted at 1 and 2 weeks, then every month. fundus fluorescein angiography examination was conducted every 3 months.There were 106 eyes from 106 patients. The number of follow-ups (3 + Q3 M: 12.4 ± 1.3 vs 3 + PRN: 12.9 ± 1.6, P = .079) and the follow-up time (3 + Q3 M: 12.7 ± 0.6 vs 3 + PRN: 12.5 ± 0.7 months, P = .121) were similar in the 2 groups. The number of injections was less in 3 + PRN than 3 + Q3 M (5.3 ± 1.0 vs 6.0 ± 0.0, P < .001) The BCVA at months 7 and 9 to 12 in the 3 + Q3 M (n = 51) group were lower than for 3 + PRN (n = 55) (all P < .05). The CRT at months 9 to 12 in the 3 + Q3 M group was lower than in the 3 + PRN group (all P < .05). There were no differences between the 2 groups regarding the exudation area during follow-up. No serious treatment-related ocular complications or serious systemic adverse events were found.The 3 + PRN and 3 + Q3 M strategies of intravitreal injection of conbercept are effective in treating exudative AMD. The 3 + Q3 M strategy needs more injection but is more effective in increasing visual acuity and reducing macular CRT than the 3 + PRN strategy.

One-Year Outcomes of 1 Dose versus 3 Loading Doses Followed by Pro Re Nata Regimen Using Ranibizumab for Neovascular Age-Related Macular Degeneration: The ARTIS Trial.

Purpose. To compare the functional and anatomical outcomes of one dose and three loading doses followed by the pro re nata (PRN) regimen in Chinese neovascular age-related macular degeneration (nvAMD) (including polypoidal choroidal vasculopathy (PCV)) patients. Methods. In this multicenter, prospective, open-label, controlled, 12-month study (ClinicalTrials.gov: NCT02810808), patients were randomized (1 : 1) to 1 dose + PRN (PRN group) or 3 loading doses + PRN (LD group) using intravitreal ranibizumab treatment. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were evaluated. The main outcome was the change in BCVA. The noninferiority limit was 5 letters. Results. Forty-five patients in the PRN group and 49 patients in the LD group finished 12-month follow-up. Each group included 4 PCV patients. The mean change in BCVA from baseline was 7.8 letters in the PRN group, compared with 10.9 letters in the LD group (P=0.344). There were no significant differences between two groups in the mean change of CRT (−159.3 μm vs. −120.5 μm) at month 12. The mean number of injections during the 12-month follow-up was 6.0 in the PRN group and 6.8 in the LD group. The proportion of patients who gained an improvement in visual acuity by 15 or more letters was 28.9% in the PRN group and 44.9% in the LD group (P=0.066). Conclusion. One dose + PRN showed noninferior visual gains than 3 loading doses + PRN regimen using ranibizumab in Chinese nvAMD and PCV patients. Number of injections in the PRN group was similar as that in the LD group but remained a potential risk of vision instability during one-year follow-up using OCT-guided retreatment criteria. This trial is registered with NCT02810808.