Long-term Outcomes of Treat and Extend Regimen of Anti-vascular Endothelial Growth Factor in Neovascular Age-related Macular Degeneration.

PURPOSE: This study describes the long-term visual and anatomic outcomes of anti-vascular endothelial growth factor (VEGF) treatment using a treat and extend dosing regimen. METHODS: This cross-sectional cohort study consisted of 224 treatment-naïve eyes with neovascular age-related macular degeneration (NV-AMD) from 202 patients that were treated with anti-VEGF agents bevacizumab, ranibizumab, and aflibercept using a treat and extend (TAE) regimen by four physician investigators in a large urban referral center from 2008 to 2015. Subjects were evaluated for visual acuity, injection frequency, and optical coherence tomography (OCT). RESULTS: Over a seven-year follow-up period (mean 3.4 years), an average 20.2 ± 14.7 injections were administered with 8.4 injections in the first year and 5.5 injections by the seventh year of remaining eyes undergoing treatment. Visual acuity was 0.70 logMAR (20/100 Snellen) at the first visit and 0.67 logMAR (20/93 Snellen) at the final visit, with 74% of eyes maintaining or gaining more than 2 lines of vision. Long-term, 45.1% of eyes achieved 20/50 or better, while 27.1% were 20/200 or worse. Of the treated patients, 61.2% received monotherapy with no difference in visual acuity outcomes or number of injections between the agents used. OCT analysis showed decreased fluid from initial to final follow-up visit: 70.1-15.6% with sub-retinal fluid (SRF) and 47.3-18.8% with intra-retinal fluid (IRF) with no difference between the agents were used. CONCLUSION: This study demonstrates that most patients (74%) improve or maintain visual acuity long-term using a TAE model with a significant portion (45.1%) achieving 20/50 or better visual acuity with sustained treatment.

Frizzled-4 Variations Associated with Retinopathy and Intrauterine Growth Retardation: A Potential Marker for Prematurity and Retinopathy.

PURPOSE: To present the association between mutations affecting the Wnt-signaling receptor protein (FZD4), inherited vitreoretinopathies, and retinopathy of prematurity (ROP). DESIGN: Retrospective analysis of prospective samples at a tertiary referral center. PARTICIPANTS: Patients referred to our practice for management of a variety of pediatric vitreoretinopathies were offered participation in an ophthalmic biobank (421 participants with vitreoretinopathies were included in this study). Full-term healthy infants (n = 98) were recruited to the study as controls. METHODS: Patients with various vitreoretinopathies were prospectively enrolled in an ophthalmic biobank, approved by the Human Investigation Committee at William Beaumont Hospital. Retrospective genetic analysis of the FZD4 gene was performed (Sanger sequencing). Participants with a diagnosis of familial exudative vitreoretinopathy (FEVR), Norrie disease, Coats' disease, bilateral persistent fetal vasculature, and ROP were reviewed for the presence of a FZD4 variant. Data retrieval included status of retinopathy (including staging when possible), gestational age (GA), birth weight (BW) (when available), and family and birth histories. MAIN OUTCOME MEASURES: The association of FZD4 variants with the presence of vitreoretinopathy. RESULTS: The sequence variation p.[P33S(;)P168S] is the most prevalent FZD4 variant and is statistically significant for ROP and FEVR (P = 4.6E-04 and P = 2.4E-03, respectively) compared with full-term newborns (P = 1.7E-01). In addition, infants expressing the sequence variation tended to have significantly lower BWs for respective GA (P = 0.04). This suggests that the FZD4 p.[P33S(;)P168S] variant may be a risk factor for retinopathy and restricted intrauterine growth. CONCLUSIONS: Testing for FZD4 gene mutations is useful in patients with suspected FEVR and ROP. The relatively high prevalence of the p.[P33S(;)P168S] variant in ROP and intrauterine growth restriction suggests that it also may be a marker for increased risk of developing ROP and preterm birth.