One-Year Outcomes of 1 Dose versus 3 Loading Doses Followed by Pro Re Nata Regimen Using Ranibizumab for Neovascular Age-Related Macular Degeneration: The ARTIS Trial.

Purpose. To compare the functional and anatomical outcomes of one dose and three loading doses followed by the pro re nata (PRN) regimen in Chinese neovascular age-related macular degeneration (nvAMD) (including polypoidal choroidal vasculopathy (PCV)) patients. Methods. In this multicenter, prospective, open-label, controlled, 12-month study (ClinicalTrials.gov: NCT02810808), patients were randomized (1 : 1) to 1 dose + PRN (PRN group) or 3 loading doses + PRN (LD group) using intravitreal ranibizumab treatment. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were evaluated. The main outcome was the change in BCVA. The noninferiority limit was 5 letters. Results. Forty-five patients in the PRN group and 49 patients in the LD group finished 12-month follow-up. Each group included 4 PCV patients. The mean change in BCVA from baseline was 7.8 letters in the PRN group, compared with 10.9 letters in the LD group (P=0.344). There were no significant differences between two groups in the mean change of CRT (-159.3 µm vs. -120.5 µm) at month 12. The mean number of injections during the 12-month follow-up was 6.0 in the PRN group and 6.8 in the LD group. The proportion of patients who gained an improvement in visual acuity by 15 or more letters was 28.9% in the PRN group and 44.9% in the LD group (P=0.066). Conclusion. One dose + PRN showed noninferior visual gains than 3 loading doses + PRN regimen using ranibizumab in Chinese nvAMD and PCV patients. Number of injections in the PRN group was similar as that in the LD group but remained a potential risk of vision instability during one-year follow-up using OCT-guided retreatment criteria. This trial is registered with NCT02810808.

Determination of Topographic Variations in Inner Retinal Blood Flow Areas in Young Chinese Subjects Using Optical Coherence Tomography Angiography.

PURPOSE: To investigate (i) topographic variations in, and (ii) establish references for, inner retinal blood flow areas of the macular region of young Chinese subjects by means of optical coherence tomography (OCT) angiography. METHODS: To measure inner retinal blood flow areas, we scanned an 8 × 8 mm2 area and centered on the fovea of 336 eyes from 170 subjects using OCT angiography. Blood flow area measurements were made from a 1-mm radius circle, centered on the fovea, and 3 mm to the fovea superiorly, inferiorly, temporally, and nasally. RESULTS: Mean inner retinal blood flow areas in the parafoveal, superior, inferior, nasal, and temporal macular regions were 1.78 ± 0.28, 1.76 ± 0.30, 1.69 ± 0.31, 1.91 ± 0.31, and 1.71 ± 0.28 mm,2 respectively. Nasal inner retinal blood flow areas were significantly larger than other macular regions (p < 0.001). Gender was significantly associated with inner retinal blood flow areas of all macular regions studied. A gender-based subgroup analysis showed that inner retinal blood flow areas in superior, inferior, nasal, and temporal macular regions were significantly larger in women than men (all p < 0.05). CONCLUSIONS: Nasal blood flow areas were larger than parafoveal blood flow areas, which were larger than superior blood flow areas, which were larger than temporal blood flow areas, which were larger than inferior blood flow areas in the macular regions studied. Gender was significantly associated with inner retinal blood flow areas in all macular regions studied.

Quantification of Macular Vascular Density Using Optical Coherence Tomography Angiography and Its Relationship with Retinal Thickness in Myopic Eyes of Young Adults.

PURPOSE: To quantify macular vascular density using optical coherence tomography angiography (OCTA) and to investigate its relationship with retinal thickness in myopic eyes of young adults. METHODS: In this cross-sectional study, 268 myopic eyes without pathological changes were recruited and divided into three groups: mild myopia (n = 81), moderate myopia (n = 117), and high myopia (n = 70). Macular vascular density was quantified by OCTA and compared among three groups. Average retinal thickness, central subfield thickness, and macular ganglion cell complex (mGCC) thickness were also evaluated and compared. Correlations among these variables were analyzed. RESULTS: There was no statistical difference in superficial (62.3 ± 5.7% versus 62.7 ± 5.9% versus 63.8 ± 5.5%) and deep macular vascular densities (58.3 ± 9.6% versus 59.2 ± 9.3% versus 60.9 ± 7.9%) among mild-myopia, moderate-myopia, and high-myopia groups (both P > 0.05). Superficial and deep macular vascular densities both had correlations with mean arterial pressure. Furthermore, superficial macular vascular density was significantly correlated with mGCC thickness. CONCLUSIONS: Varying degrees of myopia did not affect macular vascular density in young healthy adults. In addition, superficial macular vascular density, as an independent factor, was positively correlated with mGCC thickness.

CHOROIDAL THICKNESS IN UNILATERAL IDIOPATHIC MACULAR HOLE: A Cross-Sectional Study and Meta-Analysis.

PURPOSE: To investigate the choroidal thickness in unilateral idiopathic macular hole (IMH) eyes and compare them with normal control eyes using enhanced depth imaging optical coherence tomography (EDI-OCT). METHODS: In this cross-sectional study, the subfoveal choroidal thickness (SFCT) and choroidal thickness at 1 mm and 3 mm nasal, temporal, superior, and inferior to the fovea of IMH eyes and normal control eyes were measured using EDI-OCT. Univariate and multivariate linear regression analyses were performed to evaluate the correlation between choroidal thickness at various locations and clinical factors. A meta-analysis was conducted using the Stata software package to calculate the summary of weighted mean differences (WMDs). RESULTS: Thirty-two unilateral IMH patients and 32 controls were enrolled in this study. The IMH eyes had a thinner choroid than the control eyes at all macular locations (all P < 0.001). Multivariate linear regression analysis further showed that the choroidal thickness at any of the nine points was significantly thinner in association with the IMH diagnosis, as well as being somewhat thinner in association with age and axial length. The result of our cross-sectional study was consistent with the meta-analysis with a pooled WMD of -56.99 (95% confidence interval [CI]: -68.58 to -45.41) for subfoveal choroidal thickness. CONCLUSION: The study of Chinese unilateral IMH patients, along with the comprehensive meta-analysis, suggested that the choroidal thickness at all macular locations in unilateral IMH eyes significantly decreased relative to the control group.

Interocular Symmetry of Macular Ganglion Cell Complex Thickness in Young Chinese Subjects.

PURPOSE: To report interocular differences in macular ganglion cell complex (mGCC) thickness in young Chinese subjects using RTVue-100 optical coherence tomography (OCT). METHODS: This was an observational, cross-sectional study. The mGCC thickness was measured in 158young Chinese subjects using RTVue-100 OCT. The normal ranges of the interocular differences were determined as falling between the 2.5th and 97.5th percentiles. Right and left eyes were compared using a paired t test. Pearson correlation analysis was performed to assess the relationships between mGCC thickness and other potential factors. The relationships between the interocular difference in the average mGCC thickness and the potential factors were evaluated by univariate and multivariate linear regression analysis. RESULTS: The mean interocular difference in the average, superior, and inferior mGCC thickness were 0.19 ± 2.69 µm, 0.22 ±3.14 µm, and 0.25±3.34 µm, respectively, which were not statistically significant. The 2.5th and 97.5th percentiles of interocular difference for mean average mGCC thickness were -4.82µm and 4.38µm, for superior mGCC thickness, -6.67 µm and 7.04 µm, and for inferior mGCC thickness, -6.75 µm and 6.27 µm. There was a strong correlation between the right and left eyes for all the studied parameters, including spherical equivalent (SE) and axial length (AL). Interocular difference in SE (p = 0.007) were independently correlated with the interocular difference in average mGCC thickness. CONCLUSIONS: There was no significant relative interocular difference in mGCC thickness in young Chinese subjects. Interocular difference exceeding the normal limits should be considered significantly asymmetrical, and suggestive of pathology.

Resistance to anti-VEGF therapy in neovascular age-related macular degeneration: a comprehensive review.

As a progressive chronic disease, age-related macular degeneration (AMD) is the leading cause of irreversible vision impairment worldwide. Experimental and clinical evidence has demonstrated that vascular endothelial growth factor (VEGF) plays a vital role in the formation of choroidal neovascularization. Intravitreal injections of anti-VEGF agents have been recommended as a first-line treatment for neovascular AMD. However, persistent fluid or recurrent exudation still occurs despite standardized anti-VEGF therapy. Patients suffering from refractory or recurrent neovascular AMD may develop mechanisms of resistance to anti-VEGF therapy, which results in a diminished therapeutic effect. Until now, there has been no consensus on the definitions of refractory neovascular AMD and recurrent neovascular AMD. This article aims at clarifying these concepts to evaluate the efficacy of switching drugs, which contributes to making clinical decision more scientifically. Furthermore, insight into the causes of resistance to anti-VEGF therapy would be helpful for developing possible therapeutic approaches, such as combination therapy and multi-target treatment that can overcome this resistance.

[Clarifying some concepts and clinical significance of refractory or recurrent neovascular age-related macular degeneration].

Anti-VEGF therapy is currently one of the main treatments for neovascular age-related macular degeneration (nAMD). Clinically, patients under standardized anti-VEGF therapy showed different responses, of which recurrences or even insensitivity were found in some patients. However, the specific definitions of these various clinical responses are still unclarified. Therefore, to consolidate and define these concepts are of great importance regarding to future efficacy comparison, treatment response clarification and novel drug switching therapies.