CRB1-Associated Retinal Dystrophies: Genetics, Clinical Characteristics, and Natural History.

PURPOSE: To analyze the clinical characteristics, natural history, and genetics of CRB1-associated retinal dystrophies. DESIGN: Multicenter international retrospective cohort study. METHODS: Review of clinical notes, ophthalmic images, and genetic testing results of 104 patients (91 probands) with disease-causing CRB1 variants. Macular optical coherence tomography (OCT) parameters, visual function, fundus characteristics, and associations between variables were the main outcome measures. RESULTS: The mean age of the cohort at the first visit was 19.8 ± 16.1 (median 15) years, with a mean follow-up of 9.6 ± 10 years. Based on history, imaging, and clinical examination, 26 individuals were diagnosed with retinitis pigmentosa (RP; 25%), 54 with early-onset severe retinal dystrophy / Leber congenital amaurosis (EOSRD/LCA; 52%), and 24 with macular dystrophy (MD; 23%). Severe visual impairment was most frequent after 40 years of age for patients with RP and after 20 years of age for EOSRD/LCA. Longitudinal analysis revealed a significant difference between baseline and follow-up best-corrected visual acuity in the 3 subcohorts. Macular thickness decreased in most patients with EOSRD/LCA and MD, whereas the majority of patients with RP had increased perifoveal thickness. CONCLUSIONS: A subset of individuals with CRB1 variants present with mild, adult-onset RP. EOSRD/LCA phenotype was significantly associated with null variants, and 167_169 deletion was exclusively present in the MD cohort. The poor OCT lamination may have a degenerative component, as well as being congenital. Disease symmetry and reasonable window for intervention highlight CRB1 retinal dystrophies as a promising target for trials of novel therapeutics.

Long-term outcomes of anti-VEGF treatment of macular oedema due to retinal vein occlusions.

PURPOSE: retinal vein occlusion (RVO) is classified as either branch (BRVO) or central (CRVO) RVO. The gold standard treatment for macular oedema (MO) secondary to RVO is intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections. Our study aimed to compare ranibizumab and aflibercept outcomes over a maximum follow-up of five years. METHODS: this retrospective study assessed treatment-naïve RVO patients. Active disease was treated with three loading injections followed by a pro-re-nata (PRN) regimen of an anti-VEGF agent. Visual outcomes and injection frequency were analyzed, with patients stratified according to RVO subtype, anti-VEGF agent used, baseline vision, and age. RESULTS: 316 CRVO-affected eyes and 467 BRVO-affected eyes were analysed. Visual benefits between different treatments did not significantly differ, except in year 1 in ranibizumab-treated BRVO eyes. However, aflibercept-treated CRVO and BRVO eyes required significantly fewer injections during the follow up period. Furthermore, our results confirm that younger patients achieve better visual outcomes with fewer intravitreal injections. Overall, half of our patients did not require further injections after 1 year from diagnosis. CONCLUSION: the results demonstrate that anti-VEGF treatment of RVO benefits vision for up to 5 years. Our findings are the first to suggest that compared to ranibizumab, fewer aflibercept injections may be required over five years follow up. Prospective randomised trials are needed to confirm this, alongside further attention to OCT scan features and the effect of patient demographics on treatment outcomes.

Long-term outcomes of intravitreal anti-VEGF therapies in patients affected by neovascular age-related macular degeneration: a real-life study.

PURPOSE: To describe real-life data from wet age-related macular degeneration (AMD) patients treated with anti-vascular endothelial growth factors (VEGFs) and to compare our results with previous studies and clinical trials. METHODS: This retrospective monocentric cohort study analyzed 865 eyes of 780 wet-AMD patients treated with an anti-VEGF treat-and-extend regimen over a long-term follow-up period. Aflibercept and Ranibizumab were considered first-line agents whereas Bevacizumab was reserved for use on a compassionate basis in patients not meeting treatment criteria. All patients underwent a best corrected visual acuity (BCVA) assessment at each follow-up visit. RESULTS: One-year follow-up figures were available for 82.5% of patients, whilst follow-up data was recorded for 55.6%, 37.6%, 25.1%, and 15.0% of the cohort at years 2, 3, 4, and 5 respectively. Patients treated with Bevacizumab received fewer yearly injections than those treated with Ranibizumab. However, no significant difference in the number of injections per year was detected in other comparisons between groups. Whilst our data showed no significant difference in mean BCVA between the three groups, there was a gradual deterioration of visual function over time for the patient cohort as a whole. CONCLUSION: No significant differences between the 3 anti-VEGF molecules were recorded in wet-AMD patients in real-life conditions. Despite the long-term therapy, we found a slight reduction in visual function especially after the third year of treatment.

Three-year real-world outcomes of intravitreal anti-VEGF therapies in patients affected by myopic choroidal neovascularization.

PURPOSE: To describe real world data in patients affected by myopic choroidal neovascularization (CNV) treated with anti-vascular endothelial growth factors (VEGFs) and to compare our results with previous studies and clinical trials. METHODS: This retrospective monocentric cohort study analyzed 96 eyes of 96 myopic-CNV patients treated with an anti-VEGF pro-re-nata regimen over a 3-year-long follow up period. Aflibercept and Ranibizumab were considered as first-line agents whereas Bevacizumab was reserved on a compassionate basis in patients outside the criteria for treatment. All patients underwent a best-corrected visual acuity (BCVA) recording at each follow up visit. RESULTS: Our data showed that all three molecules produced significant improvements in BCVA at year 1, with no significant differences between the three drugs. Moreover, during the second year of treatment, Ranibizumab and Bevacizumab showed a significant improvement in the visual function. However, at year 3 of treatment, the data available indicated the BCVA improvement was not significant with Ranibizumab and Bevacizumab. In addition, no significant difference in the average number of injections between the three groups was detected over the follow up period. No serious adverse events were recorded, but five minor adverse events documented. CONCLUSION: Our study correlates with previous studies showing significant BCVA gains with the use of these molecules. Similarly, all three molecules seem to provide a similar duration of effects as previous studies have shown, with a low ocular adverse event rate.