This study aimed to investigate the genetic pathogeny of multiple morphological anomalies of the flagella (MMAF), which is a genetically heterogeneous disorder leading to male infertility. Nine patients with severe asthenozoospermia caused by MMAF were recruited. Whole genome sequencing and Sanger sequencing were performed, and we found that four of the nine patients were affected by the same homozygous frameshift mutation c.11726_11727delCT (p.[Pro3909ArgfsTer33]) in exon 73 of dynein axonemal heavy chain 1 (
DNAH1
) gene. The parents and the sibling of proband 1 were all identified as heterozygous carriers. This mutation was distinct from previously reported
DNAH1
mutations associated with MMAF and only affected the East Asian group. Furthermore, the variant DNAH1 protein could not be detected in spermatozoa by Western blot or immunofluorescence staining although
DNAH1
mRNA was expressed in the spermatozoa. Scanning electron microscopy and transmission electron microscopy analysis showed the anomalies in sperm flagella morphology and ultrastructure in patients carrying this genetic variant. In conclusion, our results add to knowledge of the genetic pathogeny of MMAF and further confirmed the effectiveness of genetic screening in the diagnosis of MMAF.
Background
The purpose of this study is to study the effect of repeated intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) drugs on vitreomacular interface.
Methods
Neovascular age-related macular degeneration patients who received intravitreal injections of anti-VEGF drugs were included. Eyes with severe vitreous opacity, uveitis, complicated cataract surgery and previous vitrectomy were excluded. Vitreomacular interface, best corrected visual acuity (BCVA) and central retinal thickness (CRT) assessment were performed once a month for at least 3 months. The nature and time of the change event are recorded. Groups were divided according to whether vitreomacular interface change events occurred. To analyse the risk factors of vitreomacular interface changes and their influence on treatment effect.
Results
A total of 87 eyes were evaluated. Vitreomacular interface change event occurred in 9 eyes. Pre-existing vitreomacular interface abnormality (VMIA) was a risk factor for the VMI change (P = 0.033, OR = 16.518, 95% CI: 1.258 to 216.939). 60% of interface events occurred in the first 3 months of treatment. The final BCVA of eyes with vitreomacular interface unchanged was significantly higher than that at baseline (P = 0.001), and the final CRT was also significantly lower than that at baseline (P < 0.001). The final CRT of eyes vitreomacular interface changed was significantly lower than that at baseline (P = 0.015), however, there was no statistical significance in BCVA (P = 0.468).
Conclusion
Intravitreal injection of anti-VEGF drugs has a certain probability to cause changes in the vitreomacular interface, and the risk is higher in eyes with pre-existing vitreomacular interface abnormality. The effect of intravitreal injections on the vitreomacular interface was concentrated in the first three injections, and subsequent increases in the number of injections did not significantly increase the risk of vitreomacular interface abnormality. Ophthalmologists should increase attention to the vitreomacular interface in the early stages of anti-VEGF therapy and counsel patients accordingly.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.