Effect of Intravitreal Ranibizumab on Intraretinal Hard Exudates in Eyes with Diabetic Macular Edema.

PURPOSE: To study the effect of monthly 0.3-mg intravitreal ranibizumab injections on intraretinal hard exudates (HEs) and correlate the effect with macular thickness in eyes with diabetic macular edema (DME). DESIGN: Randomized, controlled trial. METHODS: Twenty-four eyes of 24 subjects with DME were included in this institutional review board-approved, prospective longitudinal study. Subjects were randomly assigned to receive monthly intravitreal ranibizumab injections either until macular edema resolved or until both macular edema and HEs resolved. All subjects underwent spectral-domain optical coherence tomography imaging (Cirrus OCT), at baseline and monthly for 12 months. Mean HE area and mean macular thickness at baseline and month 12 were compared using a paired t test and correlated with Pearson analysis. RESULTS: The average age of the 24 subjects was 65 (±8.55) years. There was a significant decrease (P = .001) in mean HE area from baseline (0.48 ± 0.43 mm2) to month 12 (0.17 ± 0.19 mm2). There was a significant increase (P < .001) in best-corrected visual acuity from a letter score of 63.38 (±7.92) at baseline to 76.38 (±8.93) at month 12. There was no additional vision benefit for continuing to treat with monthly injections for persistent HE in the absence of macular thickening. CONCLUSION: In eyes with DME, monthly intravitreal ranibizumab injections resulted in significant reduction in intraretinal HEs that paralleled reductions in macular thickness and volume. Baseline foveal HEs were associated with worse vision outcomes, and continued treatment for persistent HEs in the absence of edema did not result in better vision.

QUANTIFICATION OF INTRARETINAL HARD EXUDATES IN EYES WITH DIABETIC RETINOPATHY BY OPTICAL COHERENCE TOMOGRAPHY.

PURPOSE: To evaluate the reproducibility of intraretinal hard exudate (HE) quantification from spectral domain optical coherence tomography (SD-OCT) images of eyes with diabetic retinopathy (DR). METHODS: Cases with diabetic macular edema were enrolled. The area of HE obtained by B-scan segmentation was compared with the area obtained by en face segmentation. RESULTS: The mean ± SD for the HE area was 1.78 ± 1.37 mm with B-scan segmentation and 0.72 ± 0.82 mm with the automated en face analysis tool; the absolute difference was 1.01 ± 0.64 mm. There was excellent correlation in total HE area between the two methods (r = 0.95, P < 0.0001). The HE volume was 0.06 ± 0.07 mm. The correlation between HE volume and en face HE area was high (r = 0.95, P < 0.001). Intergrader reproducibility yielded excellent agreement with an intraclass correlation coefficient value of 0.99 (95% CI 0.994-0.999) for the en face approach and 0.99 (95% CI 0.977-0.997) for manual segmentation. CONCLUSION: Quantification of HE in eyes with diabetic retinopathy can be performed reliably using en face segmentation and, though the en face results are consistently lower, correlates well with HE measurements obtained by exhaustive segmentation of all B-scans in dense volume optical coherence tomography (OCT).

Structural and functional implications of severe foveal dystopia in epiretinal membranes.

PURPOSE: The purpose of this study was to examine the functional and structural correlates of severe foveal dystopia in patients with epiretinal membranes. METHODS: For this retrospective study of 29 eyes with epiretinal membrane, we identified 7 eyes that had severe foveal dystopia (defined as fovea located >200 µm from its expected location) and followed the direction and rate of foveal movement pre- and postoperatively. RESULTS: Epiretinal membrane traction caused the fovea to move preoperatively at a rate of 275 µm/month from its anatomical location in 2 patients. The final preoperative foveal location was, on average, 1,217 ± 683 µm away from its expected location. Postoperatively, foveal movement toward its expected location was largest during the first month after surgery (mean = 547 ± 340 µm) and slowed down until the final follow-up position was achieved (mean = 301 ± 131 µm). Overall, the fovea moved a total of 848 ± 445 µm, allowing the fovea to correct only 32.8 ± 22.1% of the total displacement from its expected location. A univariate regression model confirmed a linear relationship between preoperative visual acuity and preoperative foveal distance from its expected anatomical location with an R of 0.759 (P = 0.0107). CONCLUSION: The extent of tractional foveal dystopia correlates with decreased visual acuity. Although all patients experienced functional and anatomical improvements with surgery, long-standing or severe foveal dystopia may be associated with permanent structural changes that limit functional outcome. Cases with extreme degrees of foveal dystopia may benefit from early intervention to prevent irreversible structural and functional changes.

Bevacizumab and ranibizumab tachyphylaxis in the treatment of choroidal neovascularisation.

AIMS: To evaluate the effect of switching to bevacizumab or ranibizumab after developing tachyphylaxis during anti-vascular endothelial growth factor (VEGF) therapy for choroidal neovascularisation (CNV). METHODS: The authors reviewed the records of all patients who received both ranibizumab and bevacizumab for treatment of CNV to identify those who developed tachyphylaxis, defined as optical coherence tomography evidence of initial decreased exudation followed by lack of further reduction or an increase in exudation. Signs of exudation included subretinal fluid (SRF), pigment epithelial detachment (PED) and/or cystoid macular oedema (CMO). RESULTS: 26 eyes were included. 10 were initially treated with bevacizumab and then changed to ranibizumab for persistent SRF, PED and/or CMO. Of these, seven had occult CNV and three had predominantly classic CNV. One eye in the occult CNV group did not respond after being switched to ranibizumab. Six eyes had a positive therapeutic response, after one injection in four eyes, and after two or three injections in one eye each. In the classic group, two responded to ranibizumab and one did not. Sixteen eyes were initially treated with ranibizumab before changing to bevacizumab. Of these, 15 had occult CNV and 1 was predominantly classic. Three of the 16 eyes failed to respond to bevacizumab; 6 improved after one injection and 5 after two injections. CONCLUSIONS: Patients with CNV who develop tachyphylaxis to ranibizumab or bevacizumab may respond to another anti-VEGF drug. The majority of cases (81%) in this series demonstrated at least some response after switching therapies.

Perineural metastasis of breast cancer treated with optic nerve sheath fenestration.

A 36-year-old woman with bilateral optic neuropathy and orbital and central nervous system metastasis from breast carcinoma developed progressive bilateral vision loss with severe optic disc swelling. She underwent optic nerve sheath fenestration of the left eye resulting in modest improvement in vision and resolution of disc edema. Optic nerve sheath fenestration is a known treatment for papilledema, but its effectiveness as a treatment for an optic neuropathy caused by perineural or intrasheath metastasis is less clear. Optic nerve sheath fenestration should be considered as a treatment option for an optic neuropathy caused by perineural or intrasheath metastasis, especially in cases where alternative treatments are not tolerated and visual loss is severe at presentation.