International Ophthalmology

, Volume 30, Issue 3, pp 267–270

Optical coherence tomography-based intravitreal ranibizumab (Lucentis) for neovascular age-related macular degeneration


  • Benjamin J. Ernst
    • Saint Louis University Eye Institute
  • Andrew J. Barkmeier
    • Cullen Eye Institute, Baylor College of Medicine
    • Saint Louis University Eye Institute
Original Paper

DOI: 10.1007/s10792-009-9324-9

Cite this article as:
Ernst, B.J., Barkmeier, A.J. & Akduman, L. Int Ophthalmol (2010) 30: 267. doi:10.1007/s10792-009-9324-9


To evaluate optical coherence tomography (OCT)-based intravitreal ranibizumab treatment for neovascular age-related macular degeneration (AMD), the charts of consecutive patients who received intravitreal ranibizumab for subfoveal choroidal neovascularization due to AMD were retrospectively reviewed. Patients with less than 6 months follow-up were excluded. OCT was performed at baseline and at monthly intervals for induction therapy. Injections were given monthly until no improvement was observed between successive OCTs. In the maintenance period, reinjections were performed for any recurrence of macular fluid on OCT. Main outcome measures were visual acuity and number of injections given. Twenty-five eyes of 22 patients with mean follow-up of 16 months [standard deviation (SD) = 3.7 months] had mean improvement of 1.6 lines of Snellen visual acuity (SD 2.9, 95% confidence interval 0.48–2.9, P = 0.008). Visual acuity was stable (≤3 lines of visual acuity lost) in 22 eyes (88%). Nine eyes (36%) gained ≥3 lines. Three eyes (12%) lost ≥3 lines. A mean of 6.0 (SD 2.7) injections were given over a follow-up period ranging from 8 to 21 months. We conclude that OCT-based intravitreal ranibizumab treatment for neovascular AMD offered excellent visual acuity results and reduced the number of injections compared with monthly dosing.


Age-related macular degenerationRanibizumabChoroidal neovascularizationOptical coherence tomography


Inhibition of vascular endothelial growth factor (VEGF) via intravitreal ranibizumab is effective in treating choroidal neovascularization (CNV) due to age-related macular degeneration (AMD) [1, 2]. Ranibizumab is a humanized monoclonal antibody fragment that inhibits all active isoforms of VEGF-A [3]. The phase III clinical trials MARINA and ANCHOR used monthly scheduled ranibizumab injections for 2 years, resulting in a mean improvement in visual acuity [1, 2]. However, frequent injections present a significant burden to patients and the health care system. Subsequent studies have evaluated various treatment regimens to maintain improvements in visual acuity while decreasing the number of injections needed, with mixed results [4, 5]. OCT-based criteria have been increasingly employed to identify macular fluid accumulation due to CNV in order to guide treatment with ranibizumab [5, 6]. We present our clinical experience using OCT to direct treatment with intravitreal ranibizumab.


The medical records of consecutive patients with subfoveal CNV due to AMD treated with intravitreal ranibizumab (Lucentis, Genentech, Inc., South San Francisco, CA, USA) at a single clinical practice were reviewed. The Saint Louis University Institutional Review Board approved the study protocol, and the study adhered to the tenets of the Declaration of Helsinki. Eyes with best-corrected visual acuity (BCVA) worse than 20/400 and patients with less than 6 months follow-up were excluded. All CNV lesion subtypes were included. Patients who had received prior treatment for CNV were included. Eyes with disciform scars or subretinal fibrosis were excluded. Patients who underwent cataract surgery and patients with signs of angioid streaks, myopic degeneration, and presumed ocular histoplasmosis syndrome were excluded. Best-corrected visual acuity was measured using Snellen charts at 20 feet by over-refraction at each visit. OCT (Stratus OCT 3, Carl Zeiss Meditec, Dublin, CA, USA) was performed at each visit.

Intravitreal ranibizumab (0.5 mg) injections were given monthly until OCT-based foveal thickness failed to improve (decrease) compared with the prior month. At this point, injections were stopped and patients were evaluated monthly. Any recurrence of fluid on OCT, such as retinal cysts, subretinal fluid or an increase in central retinal thickness greater than 10 μm, resulted in resuming monthly injections until macular fluid resolved or no further OCT improvement was documented. Then the interval between follow-up examinations was extended to the number of months it took for fluid to recur, with a maximum interval of 3 months. Snellen visual acuity was converted to logarithm of the minimum angle of resolution (logMAR) for analysis. Statistical analysis was performed using SPSS version 14.0 (SPSS Inc., Chicago, IL, USA). Means were compared using the paired Student’s t test. Statistical significance was set at P < 0.05.


Twenty-five eyes of 22 patients with mean age of 77 years followed up for a mean of 16 months [standard deviation (SD) = 3.7 months, range 8–21 months] were included in the study. There were 13 females and 9 males included. Mean BCVA improved 1.6 lines (SD 2.9, 95% confidence interval 0.48–2.9 lines, P = 0.008, t test). Mean initial BCVA was 20/106 and mean final BCVA was 20/72, corresponding to a mean gain of eight letters. Change in BCVA is summarized in Table 1.
Table 1

Change in visual acuity in eyes with age-related macular degeneration treated with intravitreal ranibizumab

Visual acuity change from baseline to final visit

Number of eyes N = 25 (%)

Mean number of injections (range)

Mean follow-up in months (range)

≥3 lines gained

9 (36%)

7.1 (3–12)

16.6 (8–21)

≥1 line to <3 lines gained

6 (24%)

5.3 (3–10)

17.2 (14–20)

No change (<1 line gained or lost)

7 (28%)

4.6 (3–6)

16.0 (10–18)

≥1 line to <3 lines lost

0 (0%)



≥3 lines lost

3 (12%)

7.3 (5–10)

14.7 (10–17)

NA Not applicable

BCVA was stable (<3 lines lost) in 22 eyes (88%), of which 15 eyes (60%) gained ≥1 of BCVA. Nine eyes (36%) gained ≥3 lines of BCVA (Fig. 1). Three eyes (12%) lost ≥3 lines of BCVA. A final BCVA of 20/40 or better was achieved in nine eyes (36%). Prior to initiating treatment with ranibizumab, five eyes (20%) had treatment with bevacizumab and one eye (4%) had prior pegaptanib. Of the six eyes with prior treatment, three eyes gained ≥3 lines of BCVA and three eyes had no change in BCVA. These results were similar to the results achieved by eyes that were treatment naïve. Overall, the mean number of injections was 6.0 (SD 2.7, range 3–12). Mean OCT central retinal thickness improved from 278 to 235 μm (P = 0.007, t test). There were two serious complications: one retinal pigment epithelium tear and one large subretinal hemorrhage.
Fig. 1

An 81-year-old female with classic choroidal neovascularization from age-related macular degeneration in the right eye without prior treatment. Baseline fundus photograph (top left) and late-phase fluorescein angiography (middle left) are shown. Optical coherence tomography (OCT) horizontal scans at baseline and at selected follow-up visits are shown on the right. Initial Snellen best-corrected visual acuity (BCVA) was 20/400 and central retinal thickness (CRT) was 297 μm by OCT. The patient was treated with intravitreal ranibizumab at the initial visit. Follow-up at month 1 showed persistent fluid on OCT with improvement in BCVA to 20/60 and CRT to 221 μm. The patient was reinjected. OCT at month 2 showed resolution of the fluid with BCVA 20/40 and CRT of 205 μm. The patient was observed monthly until fluid recurred on OCT. The patient required reinjections at months 4, 10, 14, and 17. At the final visit, month 19, BCVA was 20/60 and CRT was 219 μm. There was resolution of leakage on fluorescein angiography (bottom left) and resolution of fluid on OCT (bottom right) at 19 months after a total of six injections of ranibizumab


In this case series, the use of OCT-based intravitreal ranibizumab dosing criteria resulted in a mean improvement in BCVA with fewer injections than scheduled monthly ranibizumab dosing. The limitations of this study significantly inhibit comparisons with other studies. This study was retrospective with small sample size and no control group. Furthermore, Snellen visual acuity was used, which does not directly compare to Early Treatment Diabetic Retinopathy Study (ETDRS) logMAR acuity [7]. Although these significant differences limit comparison, the mean Snellen BCVA improvement of 1.6 (SD 2.9) lines, corresponding to a gain of eight letters, was similar to the results of prospective, controlled studies of ranibizumab [1, 2]. In the MARINA and ANCHOR studies, mean visual acuity improved by 7.2 and 11.3 ETDRS letters, respectively. Whereas these studies used monthly injections of ranibizumab over 24 months, patients in our series received a mean of 6.0 (SD 2.7) injections over a mean of 16 months while still demonstrating a clinically significant improvement in BCVA.

The variable treatment regimen used in this series was similar to that used in the PrONTO study, and the results were also similar [5]. PrONTO resulted in a mean visual acuity improvement of 9.3 letters with a mean of 5.6 injections over 12 months. In PrONTO, 82.5% of patients had no change or a gain in visual acuity, compared with 84% in this study. PrONTO was a prospective trial using ETDRS visual acuity measurements, unlike this retrospective series. Both studies were unmasked with no control group, included all subtypes of CNV, and permitted prior therapy. In PrONTO, all patients received three consecutive injections initially. Thereafter, patients were injected if they met one of five criteria: (1) visual acuity loss of ≥5 letters with macular fluid on OCT, (2) an increase in central macular thickness on OCT of at least 100 μm, (3) new macular hemorrhage, (4) new classic CNV or (5) persistent fluid on OCT. Using these criteria, the most common reason for reinjection in the PrONTO study was for ≥5 letters of VA loss occurring with <100 μm increase in central retinal thickness on OCT [5]. In contrast, our OCT-based criteria required reinjection for any recurrent macular fluid, such as retinal cysts or subretinal fluid. We feel that this more stringent standard may prevent visual loss that might occur if fluid was observed and allowed to accumulate. New subretinal hemorrhage was not an indication for reinjection in this study, but when new subretinal hemorrhage occurred in these subjects, it was accompanied by a significant increase in central macular thickness that met criteria for reinjection.

This study resulted in a similar number of injections given over a longer period of follow-up (mean 16 months) than the 12-month data from the PrONTO study. As in PrONTO, the reduced number of injections could lower the risk of serious complications such as endophthalmitis and decrease the costs of administering the medication. Further prospective studies are needed to determine a treatment regimen that can accomplish these goals while improving visual acuity in patients with neovascular AMD.


This study was supported in part by an unrestricted departmental grant from Research to Prevent Blindness. The authors have no financial disclosures to report.

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© Springer Science+Business Media B.V. 2009