PHOTOCOAGULATION VERSUS RANIBIZUMAB FOR PROLIFERATIVE DIABETIC RETINOPATHY: Should Baseline Characteristics Affect Choice of Treatment?
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SUBMITTER: Bressler SB
PROVIDER: S-EPMC6698425 | biostudies-literature | 2019 Sep
REPOSITORIES: biostudies-literature
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Project description:PurposeTo identify baseline factors associated with change in visual acuity or development of vision-impairing central-involved diabetic macular edema (DME) over 2 years when treating proliferative diabetic retinopathy (PDR) with ranibizumab or panretinal photocoagulation (PRP).DesignPost hoc analyses of randomized, multicenter clinical trial data.ParticipantsEyes completing the 2-year visit (n = 328) or without vision-impairing central-involved DME at baseline (n = 302) in Diabetic Retinopathy Clinical Research Network Protocol S.MethodsIntravitreous ranibizumab (0.5 mg/0.05 ml) or PRP.Main outcome measuresChange in visual acuity (area under the curve) and development of vision-impairing (20/32 or worse) central-involved DME over 2 years.ResultsAfter multivariable model selection with adjustment for baseline visual acuity and central subfield thickness, no factors were identified as associated with change in visual acuity or development of vision-impairing central-involved DME within the ranibizumab group. In the PRP group, worse change in visual acuity was more likely with higher hemoglobin A1c level (-0.6 letters per 1% increase; 95% confidence interval [CI], -1.2 to -0.1 letters; continuous P = 0.03), more severe diabetic retinopathy (difference between high-risk PDR or worse vs. moderate PDR or better, -2.8 letters [95% CI, -5.5 to -0.2 letters]; continuous P = 0.003), and higher mean arterial pressure (difference between ≥100 mmHg vs. <100 mmHg, -2.0 letters [95% CI, -4.6 to 0.5 letters]; continuous P = 0.009). Development of vision-impairing central-involved DME was more likely with higher hemoglobin A1c level (hazard ratio [HR] per 1% increase, 1.31 [95% CI, 1.13-1.52]; continuous P < 0.001), more severe diabetic retinopathy (HR for high-risk PDR or worse vs. moderate PDR or better, 1.46 [95% CI, 0.73-2.92]; continuous P = 0.03), and the presence of cystoid abnormalities within 500 μm of the macula center (HR, 2.90 [95% CI, 1.35-6.24]; P = 0.006).ConclusionsFor eyes managed with PRP, higher hemoglobin A1c level and more severe diabetic retinopathy were associated with less vision improvement and an increased risk of vision-impairing central-involved DME developing. When managing PDR with ranibizumab, eyes gained vision, on average, with no baseline characteristics identified as associated with visual acuity or central-involved DME outcomes.
| S-EPMC6566865 | biostudies-literature
Project description:PURPOSE:To compare patient-centered outcomes in patients with proliferative diabetic retinopathy (PDR) treated with ranibizumab vs panretinal photocoagulation (PRP). DESIGN:Randomized clinical trial. METHODS:Setting: Multicenter (55 U.S. sites). PATIENT POPULATION:Total of 216 adults with 1 study eye out of 305 adults (excluding participants with 2 study eyes, because each eye received a different treatment) with PDR, visual acuity 20/320 or better, no history of PRP. INTERVENTION:Ranibizumab (0.5 mg/0.05 mL) vs PRP. MAIN OUTCOME MEASURES:Change from baseline to 2 years in composite and prespecified subscale scores from the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25), University of Alabama Low Luminance Questionnaire (UAB-LLQ), and Work Productivity and Activity Impairment Questionnaire (WPAIQ). RESULTS:For the NEI VFQ-25 and UAB-LLQ composite scores, ranibizumab-PRP treatment group differences (95% CI) were +4.0 (-0.2, +8.3, P = .06) and +1.8 (-3.5, +7.1, P = 0.51) at 1 year, and +2.9 (-1.5, +7.2, P = .20) and +2.3 (-2.9, +7.5, P = .37) at 2 years, respectively. Work productivity loss measured with the WPAIQ was 15.6% less with ranibizumab (-26.3%, -4.8%, P = .005) at 1 year and 2.9% (-12.2%, +6.4%, P = .54) at 2 years. Eighty-three ranibizumab participants (97%) were 20/40 or better in at least 1 eye (visual acuity requirement to qualify for an unrestricted driver's license in many states) at 2 years compared with 82 PRP participants (87%, adjusted risk ratio = 1.1, 95% CI: 1.0, 1.2, P = .005). CONCLUSIONS:Though differences in some work productivity and driving-related outcomes favored ranibizumab over PRP, no differences between treatment regimens for PDR were identified for most of the other patient-centered outcomes considered.
| S-EPMC5215763 | biostudies-literature
Project description:IMPORTANCE:Panretinal photocoagulation (PRP) is the standard treatment for reducing severe visual loss from proliferative diabetic retinopathy. However, PRP can damage the retina, resulting in peripheral vision loss or worsening diabetic macular edema (DME). OBJECTIVE:To evaluate the noninferiority of intravitreous ranibizumab compared with PRP for visual acuity outcomes in patients with proliferative diabetic retinopathy. DESIGN, SETTING, AND PARTICIPANTS:Randomized clinical trial conducted at 55 US sites among 305 adults with proliferative diabetic retinopathy enrolled between February and December 2012 (mean age, 52 years; 44% female; 52% white). Both eyes were enrolled for 89 participants (1 eye to each study group), with a total of 394 study eyes. The final 2-year visit was completed in January 2015. INTERVENTIONS:Individual eyes were randomly assigned to receive PRP treatment, completed in 1 to 3 visits (n?=?203 eyes), or ranibizumab, 0.5 mg, by intravitreous injection at baseline and as frequently as every 4 weeks based on a structured re-treatment protocol (n?=?191 eyes). Eyes in both treatment groups could receive ranibizumab for DME. MAIN OUTCOMES AND MEASURES:The primary outcome was mean visual acuity change at 2 years (5-letter noninferiority margin; intention-to-treat analysis). Secondary outcomes included visual acuity area under the curve, peripheral visual field loss, vitrectomy, DME development, and retinal neovascularization. RESULTS:Mean visual acuity letter improvement at 2 years was +2.8 in the ranibizumab group vs +0.2 in the PRP group (difference, +2.2; 95% CI, -0.5 to +5.0; P?<?.001 for noninferiority). The mean treatment group difference in visual acuity area under the curve over 2 years was +4.2 (95% CI, +3.0 to +5.4; P?<?.001). Mean peripheral visual field sensitivity loss was worse (-23 dB vs -422 dB; difference, 372 dB; 95% CI, 213-531 dB; P?<?.001), vitrectomy was more frequent (15% vs 4%; difference, 9%; 95% CI, 4%-15%; P?<?.001), and DME development was more frequent (28% vs 9%; difference, 19%; 95% CI, 10%-28%; P?<?.001) in the PRP group vs the ranibizumab group, respectively. Eyes without active or regressed neovascularization at 2 years were not significantly different (35% in the ranibizumab group vs 30% in the PRP group; difference, 3%; 95% CI, -7% to 12%; P?=?.58). One eye in the ranibizumab group developed endophthalmitis. No significant differences between groups in rates of major cardiovascular events were identified. CONCLUSIONS AND RELEVANCE:Among eyes with proliferative diabetic retinopathy, treatment with ranibizumab resulted in visual acuity that was noninferior to (not worse than) PRP treatment at 2 years. Although longer-term follow-up is needed, ranibizumab may be a reasonable treatment alternative, at least through 2 years, for patients with proliferative diabetic retinopathy. TRIAL REGISTRATION:clinicaltrials.gov Identifier: NCT01489189.
| S-EPMC5567801 | biostudies-literature
Project description:PurposeTo compare rates and identify predictive factors for events that represent worsening of proliferative diabetic retinopathy (PDR) in eyes treated with panretinal photocoagulation (PRP) or ranibizumab.DesignRandomized clinical trial (55 United States sites).ParticipantsThree hundred ninety-four study eyes from 305 adults with PDR, visual acuity (VA) 20/320 or better, and no history of PRP.InterventionPanretinal photocoagulation or intravitreous ranibizumab injections (0.5 mg/0.05 ml).Main outcome measuresTime from randomization to a composite PDR-worsening outcome defined as the first occurrence of vitreous hemorrhage, retinal detachment, anterior segment neovascularization, or neovascular glaucoma.ResultsThrough 2 years, the cumulative probability of worsening PDR was 42% (PRP) versus 34% (ranibizumab; hazard ratio [HR], 1.33; 99% confidence interval [CI], 0.90 to 1.98; P = 0.063). Worse baseline levels of diabetic retinopathy severity (Early Treatment Diabetic Retinopathy Study scale) were associated with increased risk of worsening PDR, regardless of treatment group (64% [high-risk PDR or worse] vs. 23% [moderate PDR or better]; HR, 3.97; 99% CI, 2.48 to 6.36; P < 0.001). In the PRP group, eyes receiving pattern scan versus conventional single-spot PRP also were at higher risk for worsening PDR (60% vs. 39%; HR, 2.04; 99% CI, 1.02 to 4.08; P = 0.008), regardless of the number of spots placed or the number of sittings to complete the initial PRP. Eyes in both groups with vision-impairing (VA 20/32 or worse) center-involved diabetic macular edema (DME) at baseline were required to receive ranibizumab for center-involved DME. Therefore the composite outcome was compared by treatment in the subgroup of eyes that did not have vision-impairing center-involved DME at baseline. For these eyes, the rate of PDR-worsening was greater with PRP than ranibizumab (45% vs. 31%; HR, 1.62; 99% CI, 1.01 to 2.60; P = 0.008).ConclusionsIn eyes with PDR, ranibizumab resulted in less PDR worsening compared with PRP, especially in eyes not required to receive ranibizumab for center-involved DME. Although anti-vascular endothelial growth factor therapy requires a more frequent visit schedule than PRP, these findings provide additional evidence supporting the use of ranibizumab as an alternative therapy to PRP for PDR, at least through 2 years.
| S-EPMC6648671 | biostudies-literature
Project description:PURPOSE:Compare changes in retinal nerve fiber layer (RNFL) thickness between eyes assigned to intravitreous ranibizumab or panretinal photocoagulation and assess correlations between changes in RNFL and visual field sensitivity and central subfield thickness. METHODS:Eyes with proliferative diabetic retinopathy were randomly assigned to ranibizumab or panretinal photocoagulation. Baseline and annual follow-up spectral domain optical coherence tomography RNFL imaging, optical coherence tomography macular imaging, and automated static perimetry (Humphrey visual field 60-4 algorithm) were performed. RESULTS:One hundred forty-six eyes from 120 participants were analyzed. At 2 years, for the ranibizumab (N = 74) and panretinal photocoagulation (N = 66) groups, respectively, mean change in average RNFL thickness was -10.9 ± 11.7 ?m and -4.3 ± 11.6 ?m (difference, -4.9 ?m; 95% confidence interval [-7.2 ?m to -2.6 ?m]; P < 0.001); the correlation between change in RNFL thickness and 60-4 Humphrey visual field mean deviation was -0.27 (P = 0.07) and +0.33 (P = 0.035); the correlation between change in RNFL thickness and central subfield thickness was +0.63 (P < 0.001) and +0.34 (P = 0.005), respectively. CONCLUSION:At 2 years, eyes treated with ranibizumab had greater RNFL thinning than eyes treated with panretinal photocoagulation. Correlations between changes in RNFL thickness, visual field, and central subfield thickness suggest that the decrease in RNFL thickness with ranibizumab is likely due to decreased edema rather than loss of axons.
| S-EPMC6317708 | biostudies-literature
Project description:Importance:Ranibizumab is a viable treatment option for eyes with proliferative diabetic retinopathy (PDR) through 2 years. However, longer-term results are needed. Objective:To evaluate efficacy and safety of 0.5-mg intravitreous ranibizumab vs panretinal photocoagulation (PRP) over 5 years for PDR. Design, Setting, and Participants:Diabetic Retinopathy Clinical Research Network multicenter randomized clinical trial evaluated 394 study eyes with PDR enrolled February through December 2012. Analysis began in January 2018. Interventions:Eyes were randomly assigned to receive intravitreous ranibizumab (n?=?191) or PRP (n?=?203). Frequency of ranibizumab was based on a protocol-specified retreatment algorithm. Diabetic macular edema could be managed with ranibizumab in either group. Main Outcomes and Measures:Mean change in visual acuity (intention-to-treat analysis) was the main outcome. Secondary outcomes included peripheral visual field loss, development of vision-impairing diabetic macular edema, and ocular and systemic safety. Results:The 5-year visit was completed by 184 of 277 participants (66% excluding deaths). Of 305 enrolled participants, the mean (SD) age was 52 (12) years, 135 (44%) were women, and 160 (52%) were white. For the ranibizumab and PRP groups, the mean (SD) number of injections over 5 years was 19.2?(10.9) and 5.4?(7.9), respectively; the mean (SD) change in visual acuity letter score was 3.1?(14.3) and 3.0?(10.5) letters, respectively (adjusted difference,?0.6; 95% CI, -2.3 to 3.5; P?=?.68); the mean visual acuity was 20/25 (approximate?Snellen equivalent) in both groups at 5 years. The mean (SD) change in cumulative visual field total point score was -330?(645) vs -527?(635) dB in the ranibizumab (n?=?41) and PRP (n?=?38) groups, respectively (adjusted difference,?208 dB; 95% CI, 9-408). Vision-impairing diabetic macular edema developed in 27 and 53 eyes in the ranibizumab and PRP groups, respectively (cumulative probabilities: 22% vs 38%; hazard ratio,?0.4; 95% CI, 0.3-0.7). No statistically significant differences between groups in major systemic adverse event rates were identified. Conclusions and Relevance:Although loss to follow-up was relatively high, visual acuity in most study eyes that completed follow-up was very good at 5 years and was similar in both groups. Severe vision loss or serious PDR complications were uncommon with PRP or ranibizumab; however, the ranibizumab group had lower rates of developing vision-impairing diabetic macular edema and less visual field loss. Patient-specific factors, including anticipated visit compliance, cost, and frequency of visits, should be considered when choosing treatment for patients with PDR. These findings support either anti-vascular endothelial growth factor therapy or PRP as viable treatments for patients with PDR. Trial Registration:ClinicalTrials.gov Identifier: NCT01489189.
| S-EPMC6233839 | biostudies-literature
Project description:PurposeThe purpose of this study was to study the effects of panretinal photocoagulation (PRP) and intravitreal aflibercept on retinal vessel oxygen saturations, area of retinal nonperfusion, and area of neovascularization in proliferative diabetic retinopathy.MethodsThis is a prospective randomized single center study. Forty patients with proliferative diabetic retinopathy were randomized to PRP or intravitreal aflibercept treatment for 52 weeks. Retinal oximetry and ultra-widefield angiography were performed at baseline and week 52. Ultra-widefield color fundus imaging was performed at baseline, week 12, and week 52. The outcomes were retinal arterio-venous oximetry differences (AVD), area of retinal nonperfusion, and area of neovascularization in disc areas (DA).ResultsThe AVD in the PRP group increased from 36.7% at baseline to 39.7%, whereas it decreased from 33.4% to 32.5% in the aflibercept group. The difference in AVD between groups at week 52 was 4.0% (95% confidence interval, -0.08, 8.8; P = 0.10). The baseline mean area of retinal nonperfusion of 125.1 DA and 131.2 DA in the PRP and aflibercept groups increased to 156.1 DA and 158.4 DA, respectively, at week 52 (P = 0.46). The median baseline area of neovascularization decreased from 0.98 DA to 0.68 DA in the PRP group and from 0.70 DA to 0 DA in the aflibercept group at week 12 (P = 0.019). At week 52, this measured 0.24 DA in the PRP group and 0 DA in the aflibercept group (P = 0.45).ConclusionsIntravitreal aflibercept achieved an earlier and complete regression of neovascularization in proliferative diabetic retinopathy compared with PRP. There were no significant differences in global change in intravascular oxygen saturation or areas of retinal nonperfusion between the two groups by 52 weeks.
| S-EPMC6108778 | biostudies-literature
Project description:ImportancePreservation of peripheral visual field (VF) is considered an advantage for anti-vascular endothelial growth factor agents compared with panretinal photocoagulation (PRP) for treatment of proliferative diabetic retinopathy. Long-term data on VF are important when considering either treatment approach.ObjectiveTo further evaluate changes in VF throughout 5 years among eyes enrolled in the Protocol S clinical trial, conducted by the DRCR Retina Network.Design, setting, and participantsPost hoc analyses of an ancillary study within a multicenter (55 US sites) randomized clinical trial. Individuals with eyes with proliferative diabetic retinopathy enrolled in Protocol S were included. Data were collected from February 2012 to February 2018. Analysis began in June 2018.InterventionsPanretinal photocoagulation or intravitreous injections of 0.5-mg ranibizumab. Diabetic macular edema, whenever present, was treated with ranibizumab in both groups. Panretinal photocoagulation could be administered to eyes in the ranibizumab group when failure or futility criteria were met.Main outcomes and measuresMean change in total point score on VF testing with the Humphrey Field Analyzer 30-2 and 60-4 test patterns.ResultsOf 394 eyes enrolled in Protocol S, 234 (59.4%) were targeted for this ancillary study. Of these, 167 (71.4%) had VF meeting acceptable quality criteria at baseline (median [interquartile range] age, 50 [43-58] years; 90 men [53.9%]). At 5 years, 79 (33.8%) had results available. The mean (SD) change in total point score in the PRP and ranibizumab groups was -305 (521) dB and -36 (486) dB at 1 year, respectively, increasing to -527 (635) dB and -330 (645) dB at 5 years, respectively (P = .04). After censoring VF results after PRP treatments in the ranibizumab group, the 5-year mean change in total point score was -201 (442) dB. In a longitudinal regression analysis of change in total point score including both treatment groups, laser treatment was associated with a mean point decrease of 208 (95% CI, 112-304) dB for the initial PRP session, 77 (95% CI, 21-132) dB for additional PRP sessions, and 325 (95% CI, 211-439) dB for endolaser. No association was found between change in point score and the number of ranibizumab injections during the previous year (-9 per injection [95% CI, -22 to 3]).Conclusions and relevanceThe limited data available from Protocol S suggest that there are factors besides PRP associated with VF loss in eyes treated for proliferative diabetic retinopathy. Further clinical research is warranted to clarify the finding.Trial registrationClinicalTrials.gov identifier: NCT01489189.
| S-EPMC7042909 | biostudies-literature
Project description:ImportanceThe Diabetic Retinopathy Clinical Research Network Protocol S randomized clinical trial results suggest that ranibizumab is a reasonable treatment alternative to panretinal photocoagulation (PRP) when managing proliferative diabetic retinopathy (PDR), with or without concomitant baseline diabetic macular edema (DME). However, ranibizumab injections are costly. Thus, it would be useful to examine the relative cost-effectiveness of these 2 treatment modalities.ObjectiveTo evaluate incremental cost-effectiveness ratios of 0.5-mg ranibizumab therapy vs PRP for PDR.Design, setting, and participantsPreplanned secondary analysis using efficacy, safety, and resource utilization data through 2 years of follow-up at 55 US sites for 213 adults with PDR. Data were collected from February 2012 to January 2015.InterventionsIntravitreous 0.5-mg ranibizumab at baseline and as frequently as every 4 weeks based on a structured retreatment protocol or PRP at baseline for PDR. Eyes in both groups could receive ranibizumab for concomitant DME.Main outcomes and measuresIncremental cost-effectiveness ratios of ranibizumab compared with PRP evaluated within 2 prespecified subgroups for the study eye: with baseline vision-impairing (Snellen equivalent 20/32 or worse) DME and without baseline vision-impairing DME.ResultsThe study included 305 adults with PDR, the mean age was 52 years, 44% were women, and 52% were white. Of the 46 participants with PDR and vision-impairing DME at baseline, 21 were assigned to the ranibizumab group and 25 to the PRP group (plus ranibizumab for DME). Among the remaining participants without baseline vision-impairing DME, 80 and 87 were in the ranibizumab and PRP groups, respectively. For participants with and without baseline vision-impairing DME, the incremental cost-effectiveness ratios of ranibizumab therapy compared with PRP were $55 568/quality-adjusted life-year and $662 978/quality-adjusted life-year, respectively, over 2 years.Conclusions and relevanceOver 2 years, compared with PRP, 0.5-mg ranibizumab as given in this trial is within the $50 000/quality-adjusted life-year to $150 000/quality-adjusted life-year range frequently cited as cost-effective in the United States for eyes presenting with PDR and vision-impairing DME, but not for those with PDR without vision-impairing DME.Trial registrationClinicaltrials.gov Identifier: NCT01489189.
| S-EPMC5540054 | biostudies-literature
Project description:ImportanceThe DRCR Retina Network Protocol S randomized clinical trial suggested that the mean visual acuity of eyes with proliferative diabetic retinopathy (PDR) treated with ranibizumab is not worse at 5 years than that of eyes treated with panretinal photocoagulation (PRP). Moreover, the ranibizumab group had fewer new cases of diabetic macular edema (DME) with vision loss or vitrectomy but had 4 times the number of injections and 3 times the number of visits. Although 2-year cost-effectiveness results of Protocol S were previously identified, incorporating 5-year data from Protocol S could alter the longer-term cost-effectiveness of the treatment strategies from the perspective of the health care system.ObjectiveTo evaluate 5- and 10-year cost-effectiveness of therapy with ranibizumab, 0.5 mg, compared with PRP for treating PDR.Design, setting, and participantsA preplanned secondary analysis of the Protocol S randomized clinical trial using efficacy, safety, and resource utilization data through 5 years of follow-up for 213 adults diagnosed with PDR and simulating results through 10 years.InterventionsIntravitreous ranibizumab, 0.5 mg, at baseline and as frequently as every 4 weeks based on a structured retreatment protocol vs PRP at baseline for PDR; eyes in both groups could receive ranibizumab for concomitant DME with vision loss.Main outcomes and measuresIncremental cost-effectiveness ratios (ICERs) of ranibizumab therapy compared with PRP were evaluated for those with and without center-involved DME (CI-DME) and vision loss (Snellen equivalent, 20/32 or worse) at baseline.ResultsThe study included 213 adults with a mean (SD) age of 53 (12) years, of whom 92 (43%) were women and 155 (73%) were white. The ICER of the ranibizumab group compared with PRP for patients without CI-DME at baseline was $582 268 per quality-adjusted life-year (QALY) at 5 years and $742 202/QALY at 10 years. For patients with baseline CI-DME, ICERs were $65 576/QALY at 5 years and $63 930/QALY at 10 years.Conclusions and relevanceThis study suggests that during 5 to 10 years of treatment, ranibizumab, 0.5 mg, as given in the studied trial compared with PRP may be within the frequently cited range considered cost-effective in the United States for eyes presenting with PDR and vision-impairing CI-DME, but not for those with PDR but without vision-impairing CI-DME. Substantial reductions in anti-vascular endothelial growth factor cost may make the ranibizumab therapy cost-effective within this range even for patients without baseline CI-DME.Trial registrationClinicalTrials.gov identifier: NCT01489189.
| S-EPMC6813595 | biostudies-literature