Predictors for 2-Year Functional and Morphological Outcomes of a Treat-and-Extend Regimen with Ranibizumab in Patients with Diabetic Macular Edema.

PURPOSE: The purpose of the study was to investigate longer term functional and morphological outcomes and their predictors in diabetic macular edema (DME) following a treat-and-extend regimen (TER) without loading dose under ranibizumab. METHODS: Patient data were reviewed and analyzed retrospectively over a period of 24 months after initiation of TER. Best-corrected visual acuity (BCVA), treatment frequency, and quantitative and qualitative spectral-domain optical coherence tomography parameters were assessed. RESULTS: 118 eyes of 87 patients were included. A mean of 9.74 ± 2.13 injections in the first and 7.63 ± 2.29 in the second year were applied. There were significant gains of BCVA and reductions in central retinal thickness from baseline to 12 and 24 months (all p < 0.001). Percentage of eyes with an intact inner segment/outer segment (IS/OS) junction increased from 15.3% at baseline to 42.1% at 24 months (p < 0.001). An intact IS/OS junction at baseline increased the probability of having a dry retina after 12 months by 79.3% (p = 0.017) and after 24 months by 88.1% (p = 0.040). Less IS/OS disruption at baseline predicted longer maximum recurrence-free treatment intervals at 2 years (r = -0.345, p < 0.001) and better BCVA at 1 year (r = -0.347, p < 0.001). Baseline bigger intraretinal cysts were associated with more IS/OS disruption at 24 months (r = 0.305, p = 0.007). Younger age and lower BCVA at baseline were predictive for a higher BCVA gain at 24 months (p = 0.046, p < 0.001). CONCLUSION: Ranibizumab applied in a TER without loading dose in DME significantly improves visual acuity and retinal anatomical structure throughout 2 years. The evaluated predictors might help guide routine clinical treatment in DME.

Strongest Correlation Between Contrast Sensitivity and Morphological Characteristics in Bilateral nAMD.

In patients with neovascular age-related macular degeneration (nAMD) there is often an inconsistency between their subjective visual impairment and a still relatively preserved standard Early Treatment of Diabetic Retinopathy Study (ETDRS) best corrected visual acuity. Therefore, in order to better capture the specific functional defects in nAMD, other tests need to be evaluated. In a previous study, we reported contrast sensitivity of the better eye to best correlate with near distance and distance vision related quality of life in patients with bilateral nAMD. Here, we evaluated Pelli-Robson contrast sensitivity, ETDRS visual acuity, low luminance visual acuity and Radner maximum reading speed and correlated them with several morphologic parameters as measured on fundus autofluorescence imaging, optical coherence tomography and optical tomography angiography in 54 patients. A multiple regression analysis was performed which correlated each visual function parameter with the anatomic features. The results showed the strongest correlations between the total area of macular geographic atrophy as well as the percentage of geographic atrophy in the central 1 mm and contrast sensitivity. Further, the regression model selected the total area of macular geographic atrophy, the photoreceptor inner and outer segments interface disruption score, the presence of subretinal fibrosis in the central 1 mm and the central retinal thickness as the variables that explained 71% of the variation in contrast sensitivity when including all eyes. Hence, our results suggest that among the evaluated measures of vision, contrast sensitivity is best correlated with the morphologic impairment in bilateral nAMD. Thus, contrast sensitivity may complement ETDRS visual acuity in clinical trials and serve as a standard diagnostic tool in clinical practice.

Outcome Predictors of SD-OCT-Driven Intravitreal Ranibizumab in Choroidal Neovascularization due to Myopia.

PURPOSE: To analyze the efficacy and outcome predictors of SD-OCT (spectral-domain optical coherence tomography)-driven ranibizumab treatment in patients with choroidal neovascularization due to myopia (mCNV). METHODS: This prospective investigator-initiated study includes 20 patients with treatment-naïve mCNV. Evaluation included best-corrected visual acuity (BCVA), morphological SD-OCT parameters, and treatment frequency. RESULTS: From baseline to month 12, BCVA improved from 58.5 ± 16.9 to 66.1 ± 14.9 letters. Central retinal thickness (CRT) significantly decreased, and qualitative SD-OCT parameters improved. Better baseline visual acuity (VA), lower spherical equivalent, better inner/outer segment line and external limiting membrane integrity showed a significant positive effect on BCVA outcome. Less fluctuation in CRT (worst minus best CRT) indicated better BCVA at 12 months. No serious adverse events occurred. CONCLUSIONS: SD-OCT-guided intravitreal ranibizumab treatment in mCNV was efficient and safe. We determined useful predictive factors in regard to VA outcome after 12 months.

Expression of Angiogenic and Inflammatory Factors in Choroidal Neovascularisation-Derived Retinal Pigment Epithelium.

PURPOSE: Anti-angiogenic treatment is well established in the management of exudative age-related macular degeneration (AMD), but not sufficient in all patients. The characterisation of factors driving this chronic disease could serve to identify additional treatment options. The purpose of this study was to assess gene expression patterns and distinct changes in cells derived from surgically extracted choroidal neovascularisation (CNV) membranes. MATERIALS AND METHODS: The expression of >11,000 genes was analysed by means of a microarray in cells cultured from 2 late-stage CNV membranes compared to primary human retinal pigment epithelium (RPE) and ARPE-19 cells. A pathway analysis was performed to identify gene expression patterns associated with exudative AMD. RESULTS: The analysis revealed significant alterations in gene sets associated with inflammatory processes in CNV-derived cells, involving the upregulation of pro-inflammatory factors IL6, C3, and C5, and downregulation of anti-inflammatory complement factor B and complement factor I. Factors associated with angiogenesis, such as VEGFA or ANGPT2, were not significantly regulated in the 2 RPE-derived cell lines. CONCLUSION: In late-stage CNV membrane-derived RPE, gene expression was shifted towards a pro-inflammatory state. Angiogenesis-associated factors were regulated differently in the 2 CNV-derived RPE membranes. While inflammation seems to be continuously stimulated by RPE associated with late exudative AMD, this appears not to be the case with regard to angioregulatory mechanisms.

Spectral-Domain Optical Coherence Tomography-Driven Treat-and-Extend and Pro Re Nata Regimen in Patients with Macular Oedema due to Retinal Vein Occlusion: 24-Month Evaluation and Outcome Predictors.

PURPOSE: To analyse the efficacy and outcome predictors of ranibizumab using a spectral-domain optical coherence tomography (SD-OCT)-driven treat-and-extend regimen (TER) versus SD-OCT-driven pro re nata regimen (PRN) in patients with cystoid macular oedema (CME) due to branch or central retinal vein occlusion (BRVO, CRVO). METHODS: Retrospective, consecutive case series. Evaluation included best corrected visual acuity (BCVA), morphological parameters on SD-OCT, and treatment frequency. RESULTS: From baseline to months 12, 18, and 24, BCVA improved by 16.6 ± 13.1, 15.5 ± 14.4, and 16.6 ± 15.8 letters, respectively, in TER (n = 45), compared to 11.3 ± 17.0, 11.0 ± 15.0, and 10 ± 20.5 letters in PRN (n = 31) (p = 0.152, p = 0.237, p = 0.172). The mean reduction in central retinal thickness was -261 ± 189, -272 ± 188, and -264 ± 158 µm, respectively, in TER, compared to -130 ± 196, -140 ± 210, and -166 ± 207 µm in PRN (p = 0.006, p = 0.017, p = 0.064). 59% (53%) of TER and 22% (17%) of PRN patients showed no intra- or subretinal fluid on SD-OCT at 12 (24) months. Using TER, the maximum recurrence-free treatment interval increased from 8.9 ± 2.3 weeks at 12 months to 9.8 ± 2.3 and 10.5 ± 2.7 weeks at 18 and 24 months, respectively. The number of injections was significantly higher in the TER than in the PRN group. CONCLUSIONS: In CME, due to BRVO/CRVO, TER provides better morphological outcome using more injections than PRN.