Comparative evaluation of combined navigated laser photocoagulation and intravitreal ranibizumab in the treatment of diabetic macular edema

Abstract

Objective: To evaluate if a standardized combination therapy regimen, utilizing 3 monthly ranibizumab injections followed by navigated laser photocoagulation, reduces the number of total ranibizumab injections required for treatment of diabetic macular edema (DME).

Research design and methods: A 12-month, prospective comparison of 66 patients with center-involving DME: 34 patients with combination therapy were compared to 32 patients treated with ranibizumab monotherapy. All patients initially received 3 monthly ranibizumab injections (loading phase) and additional injections pro re nata (PRN). Combination therapy patients additionally received navigated laser photocoagulation after the loading phase. Main outcome measures were mean number of injections after the loading phase and change in BCVA from baseline to month 12.

Results: Navigated laser combination therapy and ranibizumab monotherapy similarly improved mean BCVA letter score (+8.41 vs. +6.31 letters, p = 0.258). In the combination group significantly less injections were required after the 3 injection loading phase (0.88 ± 1.23 vs. 3.88 ± 2.32, p< = 0.001). By month 12, 84% of patients in the monotherapy group had required additional ranibizumab injections as compared to 35% in the combination group (p< = 0.001).

Conclusions: Navigated laser combination therapy demonstrated significant visual gains in most patients. Retreatment rate and number of injections were significantly lower compared to ranibizumab monotherapy and compared to the results of conventional laser combination therapy previously reported in pivotal anti-VEGF studies.

Conflict of interest statement

Competing Interests: MK and ASN are consultants for OD-OS GmbH. The other authors have no conflicts of interest to disclose. Although MK and ASN are consultants for OD-OS GmbH, the authors can assure that this does not alter their adherence to PLOS ONE policies regarding sharing data and materials in any way.

Figures

Figure 1. Flow chart of the study.

Enrollment, Assignment and Follow-up of the patients that were included in this prospective comparison of combined navigated macula laser therapy and mono anti-VEGF therapy.

Figure 2. Course of best-corrected visual acuity (BCVA) and central retinal thickness (CRT).

(A) Change in best-corrected visual acuity (BCVA) and (B) change in central retinal thickness (CRT) during 12 months follow-up (Error bars: 95% CI). Eyes received three Rbz loading injections and combination therapy eyes additionally received Navigated MLT 115±113 days mean from baseline. Thereafter, all eyes received PRN injections. Three months from baseline, combination therapy eyes had improved by a mean 7.9±7.6 letters and monotherapy eyes had improved by 5.5±5.8 letters (difference p = 0.150) and remained stable through the PRN phase. Twelve-month values were 8.4±8.3 letters and 6.3±6.5 letters, respectively (difference p = 0.258). Similarly, during 12 months CRT in the combination therapy cohort had improved by a mean -129±170 µm and in the monotherapy cohort from by a mean −105±107 µm (difference p = 0.487).

Figure 3. Kaplan-Meier analysis of injection retreatment after the last loading phase injection.

A significantly higher proportion of Rbz monotherapy patients (84%) required injection retreatment compared to the navigated laser combination therapy cohort (35%, difference p≤0.001). Median time to retreatment was 63 and>300 days (median not reached during follow-up), respectively.