Aflibercept therapy for exudative age-related macular degeneration resistant to bevacizumab and ranibizumab.

BACKGROUND: Despite the good outcomes achieved with intravitreal angiogenic therapy, a subset of neovascular age-related macular degeneration (AMD) patients experience resistance to therapy after repeated injections. Switching drugs could offer benefit to this group of patients. PURPOSE: To determine visual and anatomical outcomes in a cohort of neovascular AMD patients resistant to repeated injections of bevacizumab/ranibizumab after switching to aflibercept therapy. METHODS: This was a retrospective chart review of patients who had a diagnosis of neovascular AMD and persistent intraretinal (IRF) and/or subretinal fluid (SRF) on optical coherence tomography (OCT) for at least 3 months despite monthly bevacizumab and/or ranibizumab injections prior to transition to aflibercept. We reviewed patients' records and OCT images obtained at baseline, 1, 3, 6 and 12 months after transition to aflibercept. Data collected included demographics, best-corrected visual acuity (BCVA), number of injections received and the occurrence of any adverse events. Studied OCT parameters included central macular thickness (CMT) values and the presence or absence of SRF, IRF and/or pigment epithelial detachment (PED) at each visit. RESULTS: We included 53 eyes of 48 patients. Mean change in BCVA from baseline was 0.05 ± 0.13 (P = 0.01) at M1, 0.04 ± 0.16 (P = 0.08) at M3, 0.01 ± 0.22 (P = 0.9) at M6, and 0.02 ± 0.28 (P = 1) at M12, while the mean change in CMT from baseline was 64 ± 75 µm (P < 0.0001) at M1, 42 ± 85 µm (P = 0.002) at M3, 47 ± 69 µm (P < 0.0001) at M6, and 46 ± 99 µm (P = 0.001) at M12. The percentage of eyes with SRF decreased from 77.4% at baseline to 39.6% at M1, then increased to 47.2% at M3, then decreased to 43.4% at M6, and to 41.5% at M12 (All p < 0.001, compared to baseline). Compared to baseline, there was a statistically significant decrease in the percentage of eyes having IRF from 47.2 to 20.8% at M1 (p < 0.001), 30.2% at M3, 24.5% at M6 and 26.4% at M12 (p < 0.01, each). The number of bevacizumab and/or ranibizumab injections (7.36 ± 1.85) was significantly higher than that of aflibercept (6.47 ± 2.45, p = 0.001). A significant direct relationship between CMT reduction and BCVA improvement was demonstrated at M1 (p = 0.01, r = 0.36), M3 (p = 0.03, r = 0.30) and M12 (p = 0.03, r = 0.30). Eyes with IRF had significantly poorer BCVA than eyes without IRF at baseline (p = 0.02) and M3 (p = 0.04). CONCLUSION: Switching to intravitreal aflibercept therapy in a cohort of neovascular AMD patients resistant to chronic bevacizumab and/or ranibizumab injections can lead to significant visual improvement in the short term and sustained reduction of central macular thickness over 1 year of followup.

Macular Atrophy in Neovascular Age-Related Macular Degeneration with Monthly versus Treat-and-Extend Ranibizumab: Findings from the TREX-AMD Trial.

PURPOSE: To compare the enlargement rate of macular atrophy (ERMA) in eyes treated with ranibizumab monthly or using a treat-and-extend (TREX) regimen for neovascular age-related macular degeneration (AMD) or fellow control eyes, as well as analyze risk factors for macular atrophy (MA) development and progression. DESIGN: Eighteen-month, multicenter, randomized, controlled clinical trial. PARTICIPANTS: Sixty patients with treatment-naïve neovascular AMD in 1 eye randomized 1:2 to monthly or TREX ranibizumab. METHODS: Patients' study and fellow eyes were followed for 18 months using spectral-domain optical coherence tomography (SD OCT) and fundus autofluorescence (FAF) imaging. The MA was quantified on FAF images using Heidelberg Region Finder software (Heidelberg Engineering, Heidelberg, Germany), with suspected areas of atrophy confirmed by SD OCT and infrared reflectance imaging. For eyes without baseline MA yet developed MA by 18 months, intervening visits were assessed to determine the first visit at which MA appeared to define progression rates. Foveal choroidal thickness (FCT), subretinal hyperreflective material (SHRM), and pigment epithelial detachment (PED), were assessed at baseline to determine whether they influenced MA progression. MAIN OUTCOME MEASURES: Mean ERMA at 18 months. Relationship between visual acuity and MA, and the baseline risk factors for ERMA were also assessed. RESULTS: The final analysis cohort included 88 eyes in 3 groups: monthly (n = 19), TREX (n = 30), and control fellow eyes (n = 39). Mean ERMA over 18 months was 0.39±0.67 (monthly), 1.1±1.9 (TREX), and 0.49±1 mm2 (control, P = 0.12). Mean ERMA per group among the 40.9% (n = 36) of baseline patients with MA was 0.9±1, 1.9±2.2, and 1±1.3 mm2, respectively (P = 0.31). The incidence rate of MA in the 3 groups was 40%, 0%, and 8.3%, respectively. Mann-Whitney U test revealed a statistically significant association between baseline FCT (127±46 vs. 155±55 µm, P = 0.01) and SHRM thickness (106±131 vs. 50±85 µm, P = 0.02) on MA. In eyes with no baseline MA, presence of SHRM, SHRM, and PED thickness, and presence of baseline hemorrhage were all significant predictors of new MA development (P = 0.04, 0.01, 0.04, 0.004, 0.01, respectively). CONCLUSIONS: Ranibizumab did not show a statistically significant influence on new MA development in eyes with neovascular AMD, whether dosed monthly or per TREX regimen. The FCT, SHRM thickness, and hemorrhage at baseline were all significant predictors of new MA.

Host immune cellular reactions in corneal neovascularization.

Corneal neovascularization (CNV) is a global important cause of visual impairment. The immune mechanisms leading to corneal heme- and lymphangiogenesis have been extensively studied over the past years as more attempts were made to develop better prophylactic and therapeutic measures. This article aims to discuss immune cells of particular relevance to CNV, with a focus on macrophages, Th17 cells, dendritic cells and the underlying immunology of common pathologies involving neovascularization of the cornea. Hopefully, a thorough understanding of these topics would propel the efforts to halt the detrimental effects of CNV.

Keratoconus correction using a new model of intrastromal corneal ring segments.

PURPOSE: To evaluate the optical value of a new model of intrastromal corneal ring segments (ICRS) (Keratacx Plus) in patients with keratoconus and to quantify subsequent changes in corneal topography and asphericity. SETTING: Private practice. DESIGN: Prospective case series. METHODS: This study comprised patients who had primary keratoconus or keratectasia after laser in situ keratomileusis (LASIK); none wore contact lenses. Rings were implanted through tunnels created manually or with a femtosecond laser. All eyes had clear visual axes and corneal thickness over 450 µm at the incision site. Preoperative and postoperative pachymetry images were acquired. Results were analyzed using a matched-pair t test and the Kolmogorov-Smirnov test. RESULTS: Twenty-nine eyes (24 patients; mean age 30.1 years ± 10.6 [SD]) were evaluated. The ICRS significantly increased uncorrected and corrected visual acuities from 0.05 to 0.16 and from 0.17 to 0.5, respectively (z = 4.7, P < .001). They reduced the median spherical error from -4.0 to -0.5 diopters (D) (P < .001) and median cylindrical error from -4.4 to -2.5 D (P < .001). All topographic parameters were reduced, including maximum keratometry (K) (49.4 D versus 45.1 D), minimum K (49.4 D versus 45.1 D), mean K (51.4 D versus 48.4 D), astigmatism (-2.0 D versus -0.5 D), and asphericity (eccentricity 0.49 versus 0.23) (all P < .001). CONCLUSIONS: The ICRS provided topographic and visual improvement in keratoconus and post-LASIK keratectasia. Variance in surgical outcomes with manual versus femtosecond tunneling and the effect of different ring sizes are yet to be studied.