Differential diagnosis of macular edema of different pathophysiologic origins by spectral domain optical coherence tomography.

PURPOSE: To develop a classification approach based solely on spectral domain optical coherence tomography to differentiate macular edema (ME) of different disease entities and to determine underlying pathology. METHODS: A cross-sectional study including 153 participants: 27 with Irvine-Gass, 31 with uveitic ME, 24 with ME after branch retinal vein occlusion, 13 with central retinal vein occlusion, 44 with diabetic ME, and 14 controls. Spectral domain optical coherence tomography was graded according to a standardized reading protocol. Grading characteristics were: ME pattern in the central line (horizontal/vertical) and in volume scans, distribution of cysts in Early Treatment Diabetic Retinopathy Study grid, morphologic features, and quantitative parameters such as individual layer thickness. The parameters in a best-fitting multivariate model were evaluated for reliability to predict the underlying pathology using a leave-one-out crossover-validation analysis. To evaluate clinical reliability, two masked clinicians graded spectral domain optical coherence tomography images according to the assessed parameters. RESULTS: The best-fitting multivariate model revealed that microfoci, ME pattern in vertical line scan, and foveal retinal nerve fiber layer thickness are the best indicators of the underlying pathology of ME. Classification accuracy of this model was 96%, mean cross-validated test classification accuracy was 84% (r² = 0.95, P < 0.0001). Clinical relevance was examined with 2 independent readers, yielding classification accuracies of 86% in both cases. CONCLUSION: Macular edema demonstrates characteristic patterns, morphologic features, and layer thicknesses dependent on the underlying disease process. Diagnostic recognition of these features may allow clinical and automated disease identification based primarily on spectral domain optical coherence tomography analysis.

Macula-On Versus Macula-Off Pseudophakic Rhegmatogenous Retinal Detachment Following Primary 23-Gauge Vitrectomy Plus Endotamponade.

AIM: To evaluate anatomical and functional outcomes of macula-on and macula-off rhegmatogenous retinal detachment (RRD) after 23-gauge vitrectomy and gas endotamponade, in eyes after successful cataract surgery. METHODS: Forty-six pseudophakic eyes of 46 consecutive patients who underwent surgery for RRD repair were included. Based on the severity degree and extension of the RRD, diluted C3F8, SF6 or C2F6 gases were used for endotamponade. Patients were followed 1 month, 3 months, 6 months and 12 months after surgery. Main outcome variables were functional and anatomic outcomes till 12 months after surgery. RESULTS: Proliferative vitreoretinopathy of grade B or C was observed in 43%. C3F8 was used in 59%, SF6 in 28% and C2F6 in 13%. Reattachment after the first intervention was achieved in 89%. Preoperatively, 63% of patients presented with fovea-off retinal detachment. No intraoperative complications were registered. Preoperatively, eyes with macula-on RRD had a logMar BCVA of 0.3 ± 0.6 compared with 1.2 ± 0.7 in the macula-off group (p = 0.01). The mean visual acuity significantly improved to 0.06 ± 0.1 logMar in macula-on eyes and to 0.2 ± 0.3 logMar in macula-off eyes at 12 months (p = 0.01 compared to baseline and p = 0.04 between both the groups). The mean final postoperative CRT was 318 ± 48 µm in the macula-on group compared with 305 ± 71 µm in the macula-off group (p = 0.5). CONCLUSIONS: Even morphological improvement after 23-gauge vitrectomy and gas endotamponade was comparable between macula-on and macula-off eyes, macula-off RRDs showed delayed visual rehabilitation. Both groups showed significant visual acuity improvement until 12 months, however, macula-on RRDs showed significantly more improvement than macula-off RRDs.

Anti-VEGF treatment in branch retinal vein occlusion: a real-world experience over 4 years.

PURPOSE: To determine long-term outcome of intraocular antagonism of vascular endothelial growth factor (VEGF) in macular oedema (ME) secondary to branch retinal vein occlusion (BRVO). METHODS: A total of 28 consecutive patients were treated with either intravitreal bevacizumab (IVB) or intravitreal ranibizumab (IVR) in the first series and were evaluated after a mean follow-up of 5 years for their functional and anatomical outcome. RESULTS: Time between onset of macular oedema and initial treatment was 5.2 ± 0.4/0.1 ± 0.1 (IVB/IVR) months. A mean of 4 intravitreal injections were given per patients in the first 6 months. In months 7-12 intravitreal injections decreased to 2 and further decreased in the second year (months 13-18: 1.14; months 19-24: 0.5) and third year (months 25-30: 0.4; months 31-36: 0.2). After the fourth year, only two of the 28 patients received further treatment. Average visual acuity (VA) increased by 16 letters after 1 year (p < 0.01) and although not statistically significantly, by a mean of 5 letters (p = 0.3) at long-term evaluation (IVB-group). However, after mean of 5 years, central retinal sensitivity (CRS) improved by 3.6 dB (p = 0.01) and central retinal thickness (CRT) decreased by 161 µm (p = 0.02). In the IVR-group, VA and CRS increased significantly (31 letters and respectively 4.4 dB, p < 0.001) and CRT decreased by 229 µm (p < 0.001) after long-term follow-up. Final functional results were significantly better in patients with treatment initiation <3 months (79 versus 55 letters, p = 0.01). Microvascular abnormalities were detected in 88% (21 of 24 patients), hyperfluorescence in 42% (10 of 24 patients) on wide-field fluorescein angiography in both groups. CONCLUSIONS: Inhibition of VEGF provides substantial long-term benefits for patients with ME secondary to BRVO. Early treatment with anti-VEGF agents and extended therapeutic surveillance was associated with improved visual recovery.

Lipoxygenase mediates invasion of intrametastatic lymphatic vessels and propagates lymph node metastasis of human mammary carcinoma xenografts in mouse.

In individuals with mammary carcinoma, the most relevant prognostic predictor of distant organ metastasis and clinical outcome is the status of axillary lymph node metastasis. Metastases form initially in axillary sentinel lymph nodes and progress via connecting lymphatic vessels into postsentinel lymph nodes. However, the mechanisms of consecutive lymph node colonization are unknown. Through the analysis of human mammary carcinomas and their matching axillary lymph nodes, we show here that intrametastatic lymphatic vessels and bulk tumor cell invasion into these vessels highly correlate with formation of postsentinel metastasis. In an in vitro model of tumor bulk invasion, human mammary carcinoma cells caused circular defects in lymphatic endothelial monolayers. These circular defects were highly reminiscent of defects of the lymphovascular walls at sites of tumor invasion in vivo and were primarily generated by the tumor-derived arachidonic acid metabolite 12S-HETE following 15-lipoxygenase-1 (ALOX15) catalysis. Accordingly, pharmacological inhibition and shRNA knockdown of ALOX15 each repressed formation of circular defects in vitro. Importantly, ALOX15 knockdown antagonized formation of lymph node metastasis in xenografted tumors. Furthermore, expression of lipoxygenase in human sentinel lymph node metastases correlated inversely with metastasis-free survival. These results provide evidence that lipoxygenase serves as a mediator of tumor cell invasion into lymphatic vessels and formation of lymph node metastasis in ductal mammary carcinomas.