Rationale for the diabetic retinopathy clinical research network treatment protocol for center-involved diabetic macular edema.

OBJECTIVE: To describe the underlying principles used to develop a web-based algorithm that incorporated intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment for diabetic macular edema (DME) in a Diabetic Retinopathy Clinical Research Network (DRCR.net) randomized clinical trial. DESIGN: Discussion of treatment protocol for DME. PARTICIPANTS: Subjects with vision loss resulting from DME involving the center of the macula. METHODS: The DRCR.net created an algorithm incorporating anti-VEGF injections in a comparative effectiveness randomized clinical trial evaluating intravitreal ranibizumab with prompt or deferred (≥24 weeks) focal/grid laser treatment in eyes with vision loss resulting from center-involved DME. Results confirmed that intravitreal ranibizumab with prompt or deferred laser provides superior visual acuity outcomes compared with prompt laser alone through at least 2 years. Duplication of this algorithm may not be practical for clinical practice. To share their opinion on how ophthalmologists might emulate the study protocol, participating DRCR.net investigators developed guidelines based on the algorithm's underlying rationale. MAIN OUTCOME MEASURES: Clinical guidelines based on a DRCR.net protocol. RESULTS: The treatment protocol required real-time feedback from a web-based data entry system for intravitreal injections, focal/grid laser treatment, and follow-up intervals. Guidance from this system indicated whether treatment was required or given at investigator discretion and when follow-up should be scheduled. Clinical treatment guidelines, based on the underlying clinical rationale of the DRCR.net protocol, include repeating treatment monthly as long as there is improvement in edema compared with the previous month or until the retina is no longer thickened. If thickening recurs or worsens after discontinuing treatment, treatment is resumed. CONCLUSIONS: Duplication of the approach used in the DRCR.net randomized clinical trial to treat DME involving the center of the macula with intravitreal ranibizumab may not be practical in clinical practice, but likely can be emulated based on an understanding of the underlying rationale for the study protocol. Inherent differences between a web-based treatment algorithm and a clinical approach may lead to differences in outcomes that are impossible to predict. The closer the clinical approach is to the algorithm used in the study, the more likely the outcomes will be similar to those published. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Effects of ranibizumab on exudative disciform scars.

BACKGROUND AND OBJECTIVE: To evaluate the effect of intravitreal ranibizumab in patients with leaking disciform scars. PATIENTS AND METHODS: In this retrospective case series, 31 eyes received one or two ranibizumab injections for treatment of choroidal neovascularization. Visual acuity, central retinal thickness, and macular volume were measured prior to injection and at 1-month follow-up. RESULTS: After one injection (n = 31), mean optical coherence tomography (OCT) central foveal thickness decreased from 317 to 242 microm (P = .00016). Mean OCT macular volume decreased from 7.89 to 6.80 mm3 (P = .00019). After two injections (n = 12), mean OCT central foveal thickness decreased from 310 to 248 microm following the second injection (P = .04). Mean OCT macular volume decreased from 7.80 to 6.43 mm3 at 1-month follow-up after a second injection (P = .006). There was no significant change in visual acuity after injections. CONCLUSION: In the short-term, ranibizumab decreases the leakage associated with choroidal neovascularization in chronic macular degeneration.

Diurnal variation in retinal thickening measurement by optical coherence tomography in center-involved diabetic macular edema.

OBJECTIVE: To evaluate diurnal variation in retinal thickness measured with optical coherence tomography (OCT) in patients with center-involved diabetic macular edema. METHODS: Serial OCT3 measurements were performed in 156 eyes of 96 subjects with clinically diagnosed diabetic macular edema and OCT central subfield retinal thickness of 225 microm or greater at 8 am. Central subfield thickness was measured from OCT3 retinal thickness maps at 6 points over a single day between 8 am and 4 pm. A change in central subfield thickening (observed thickness minus mean normal thickness) of at least 25% and of at least 50 microm at 2 consecutive points or between 8 am and 4 pm was considered to have met the composite outcome threshold. RESULTS: At 8 am, the mean central subfield thickness was 368 microm and the mean visual acuity was 66 letters (approximately 20/50). The mean change in relative central subfield retinal thickening between 8 am and 4 pm was a decrease of 6% (95% confidence interval, -9% to -3%) and the mean absolute change was a decrease of 13 microm (95% CI, -17 to -8). The absolute change was significantly greater in retinas that were thicker at 8 am (P<.001) but the relative change was not (P = .14). The composite threshold of reduction in central subfield thickening (as defined above) was observed in 5 eyes of 4 subjects (3% of eyes; 95% CI, 1% to 8%) while 2 eyes of 2 subjects (1%; 95% CI, 0% to 5%) had an increase in central subfield thickening of this same magnitude. The maximum decrease was observed at 4 pm in all 5 eyes. CONCLUSION: Although on average there are slight decreases in retinal thickening during the day, most eyes with diabetic macular edema have little meaningful change in OCT central subfield thickening between 8 am and 4 pm.

Preoperative visual acuity as a prognostic indicator for laser treatment of macular edema due to branch retinal vein occlusion.

BACKGROUND AND OBJECTIVE: To determine the visual outcome of laser treatments for macular edema due to branch retinal vein occlusion (BRVO) in patients with a preoperative visual acuity (VA) of 20/200 or worse compared to patients with a preoperative VA of better than 20/200. PATIENTS AND METHODS: Records of 88 patients with macular edema secondary to BRVO undergoing laser treatment from 1984 to 2003 were reviewed. Mean VA was measured before and after each treatment and after the final treatment. RESULTS: All patients received between one and five laser treatments. Preoperative VA was better than 20/200 in 56 patients (group 1) and 20/200 or worse in 32 patients (group 2). Patients in group 1 had a mean improvement of 0.48 lines and 57% had a final VA of 20/40 or better. Patients in group 2 had a mean improvement of 1.69 lines and 20% had a final VA of 20/40 or better. CONCLUSIONS: Patients with poor VA (20/200 or worse) secondary to macular edema due to BRVO responded positively to laser treatment. The level of preoperative VA can be a useful predictor of visual outcome. These patients should consider laser treatment before alternative, more aggressive approaches.

A pilot study of multiple intravitreal injections of ranibizumab in patients with center-involving clinically significant diabetic macular edema.

OBJECTIVE: To evaluate the biologic activity of multiple intravitreal injections of ranibizumab in patients with center-involving clinically significant diabetic macular edema (DME) and to report any associated adverse events. DESIGN: Single-center, open-label, dose-escalating pilot study. PARTICIPANTS: A total of 10 eyes of 10 patients (mean age, 69.3 years [range, 59-81]) with DME involving the center of the macula and best-corrected visual acuity (BCVA) in the study eye between 20/63 and 20/400. INTERVENTION: Three intravitreal injections of ranibizumab (0.3 mg or 0.5 mg each injection) administered on day 0, month 1, and month 2, and observation until month 24. MAIN OUTCOME MEASURES: Primary end points were the frequency and severity of ocular and systemic adverse events. Secondary end points were BCVA and measurement of retinal thickness by optical coherence tomography. RESULTS: Of the 10 patients enrolled, 5 received 0.3-mg and 5 received 0.5-mg ranibizumab. Intravitreal injections of ranibizumab were well tolerated. No systemic adverse events were reported. Five occurrences of mild to moderate ocular inflammation were reported. At month 3, 4 of 10 patients gained > or =15 letters, 5 of 10 gained > or =10 letters, and 8 of 10 gained > or =1 letters. At month 3, the mean decrease in retinal thickness of the center point of the central subfield was 45.3+/-196.3 microm for the low-dose group and 197.8+/-85.9 microm for the high-dose group. CONCLUSIONS: Ranibizumab appears to be a well-tolerated therapy for patients with DME. This pilot study demonstrates that ranibizumab therapy has the potential to maintain or improve BCVA and reduce retinal thickness in patients with center-involved clinically significant DME.

Multiple laser treatments for macular edema attributable to branch retinal vein occlusion.

PURPOSE: To report the visual outcome of multiple laser treatments for macular edema attributable to branch retinal vein occlusions (BRVO) and to determine if any prognostic factors exist for improvement. DESIGN: Retrospective chart review. METHODS: A private practice with four vitreoretinal surgeons performed laser treatments on 88 eyes of 88 patients with macular edema secondary to BRVO from 1984 to 2003. Mean preoperative and postoperative visual acuities were collected after each laser treatment. Final visual acuities were also documented. RESULTS: All 88 patients received at least one laser treatment, and 46 patients of the initial 88 underwent multiple treatments. Overall, forty-one (46.6%) of the total 88 patients improved by 2 or more lines, whereas 33 patients (37.5%) were within 1 line of the preoperative vision, and 14 patients (15.9%) worsened by 2 or more lines. The mean final visual improvement was 0.92 lines for all 88 patients. The group of patients that responded favorably to the first laser treatment (n = 37) showed an overall improvement of 3.5 lines. However, patients who responded poorly to the first laser treatment resulted in an overall worsening of vision by 0.96 lines. CONCLUSIONS: Our study found that multiple laser treatments can improve visual acuity and resolve macular edema and that each additional laser treatment gives a patient a modest chance of visual improvement. A positive or stable visual response to first laser treatment portends a favorable prognosis with subsequent laser treatments.