Novel p.G1344E mutation in FBN1 is associated with ectopia lentis.

BACKGROUND: Ectopia lentis refers to dislocation or subluxation of the crystalline lens. Fibrillin-1, encoded by FBN1, is an important microfibrillar structural component that is specifically required for the suspensory ligament of the lens. FBN1 mutations may cause abnormal structure of microfibrils and has been associated with a broad spectrum of clinical phenotypes. In this study, we characterised a Chinese dominant family with late-onset isolated ectopia lentis caused by a novel missense FBN1 mutation. METHODS: Eight family members, including four patients with suspected isolated ectopia lentis, were recruited from Shanghai. Clinical data and family history of the proband and other affected family members were collected. Ophthalmic examination, systemic examination and echocardiography were performed. Whole exome sequencing and Sanger sequencing were used to detect potential pathogenic variants. RESULTS: A novel heterozygous missense mutation c.4031 G>A/p.Gly1344Glu in exon 33 of FBN1 was identified. This mutation was detected in all affected family members and led to specific ocular system phenotypes (ectopia lentis, microspherophakia and secondary glaucoma) with minor skeletal involvement (hallux valgus). CONCLUSION: The novel c.4031G>A mutation in FBN1 is a likely pathogenic mutation for isolated ectopia lentis. Our study expands the spectrum of FBN1 mutations and contributes to better comprehension of genotype-phenotype correlations of ectopia lentis disease.

Intraocular Pharmacokinetics and Safety of Subretinal Injection Compared with Intravitreal Application of Conbercept in Vitrectomized Rabbit Eyes.

PURPOSE: To evaluate the ocular pharmacokinetic properties of subretinal conbercept injection in vitrectomized rabbit eyes and to compare them with those by intravitreal injection. METHODS: The following groups of New Zealand white rabbits received conbercept injections (0.5 mg/0.05 ml): a subretinal group (subretinal injection in vitrectomized eyes), an intravitreal group (intravitreal injection in vitrectomized eyes), and a control group (intravitreal injection in nonvitrectomized eyes). Drug concentrations in the aqueous humor (AH), the vitreous humor (VH), and the retina were measured by the enzyme-linked immunosorbent assay (ELISA), and pharmacokinetic parameters were calculated. Ophthalmic B-ultrasonography, electroretinogram (ERG), and hematoxylin and eosin (H&E) staining were performed to evaluate the safety of subretinal injection. RESULTS: On the 28th day after injection, the drug level in the subretinal group was significantly higher than that in the intravitreal group in the AH (0.90 ± 0.25 µg/ml and 0.11 ± 0.07 µg/ml and 0.11 ± 0.07 P < 0.001, respectively) and the VH (5.00 ± 3.86 µg/ml and 0.11 ± 0.07 µg/ml and 0.11 ± 0.07 P < 0.001, respectively) and the VH (5.00 ± 3.86 P < 0.001, respectively) and the VH (5.00 ± 3.86 P < 0.001, respectively) and the VH (5.00 ± 3.86 . CONCLUSIONS: Our study indicates that applying conbercept by subretinal injection can reduce the drug clearance rate and sustain a long maintenance period in ocular tissue, which suggests that subretinal conbercept injection may be a potentially valuable treatment option.

Traumatic endophthalmitis and the outcome after vitrectomy in young children.

AIM: To explore the traumatic endophthalmitis in young children and the outcome of pars plana vitrectomy (PPV). METHODS: Twenty-two eyes of 22 cases of young children consecutive pediatric traumatic endophthalmitis treated and followed up between September 2014 and May 2018 were included. Aqueous humor or vitreous samples were taken for bacterial culture and sensitivity tests. Intravitreal antibiotics (norvancomycin and ceftazidime) injection, combined with 23-gauge PPV, were administered in 22 eyes. Silicone oil (SO; 5000 centistoke) tamponade or perfluoropropane gas (C3F8) was used in all patients. Main outcome measures were best-corrected visual acuity (BCVA) and retinal attachment, the ratio of penetrating injury, and the existence of intraocular foreign body. RESULTS: The mean age of patients was 6.9±2.2 (range, 3-10)y. All injured eyes suffered from penetrating ocular injury with retained intraocular foreign body in one eye. Bacterial culture was positive in only 2 eyes. The mean follow-up time was 21.1±4.7 (range, 12-30)mo. In the primary PPV, intravitreal antibiotics was administrated in all eyes, SO in 18 eyes, and C3F8 in 4 eyes. The secondary operation of SO removal and C3F8 endotamponade was performed in 16 eyes and a second SO endotamponade due to emulsification of the oil and retinal detachment (RD) was operated in 7 eyes underwent 3 to 11.5mo after primary PPV. A third operation was done in 7 eyes. The final intraocular pressure (IOP) was 8.9±1.8 (range, 6.9-11.4) mm Hg. The final BCVAs were 20/200 or better in 5, counting fingers in 2, and light perception to hand movement in 8 eyes. Whose (66.7%) had retinal injury exhibited worse BCVA (P=0.019, Fisher's exact test). Eyes underwent SO tamponade exhibited worse final BCVA than that with C3F8 in the primary PPV (P=0.026, Fisher's exact test). CONCLUSION: Traumatic endophthalmitis in children is generally more severe and associated with more complicated surgical procedures. Most patients have retinal injury need multiple operations and the final BCVA is poor. Prevention of ocular trauma, especially in children, is still critical.

Intraocular pharmacokinetics of anti-vascular endothelial growth factor agents by intraoperative subretinal versus intravitreal injection in silicone oil-filled eyes of proliferative diabetic retinopathy: a randomized controlled pilot study.

PURPOSE: Intraoperative subretinal anti-vascular endothelial growth factor (VEGF) injections have been used clinically in some case, but the pharmacokinetic characteristics have not yet been determined. In this pilot study, we investigate the pharmacokinetic parameters of anti-VEGF agents by intraoperative subretinal or intravitreal injection in silicone oil (SiO)-filled eyes of patients with proliferative diabetic retinopathy (PDR). METHODS: Randomized controlled trial including 13 patients (16 eyes) with PDR underwent pars plana vitrectomy (PPV) with SiO tamponade and randomly received a subretinal (8 eyes) or intravitreal (8 eyes) conbercept injection (0.5 mg/0.05 ml) intraoperatively. Aqueous humour (AH) was obtained on the 1st, 3rd, 7th, 10th, 14th, 21st and 28th day after the injection. Drug concentrations in the AH were determined by enzyme-linked immunosorbent assay (ELISA). The last best-corrected visual acuity (BCVA) was examined 6 months postoperatively. RESULTS: The clearance rate of anti-VEGF agents by subretinal injection was reduced in vitrectomized eyes with SiO tamponade (p < 0.05). With the same drug dose, subretinal injection (5.49 ± 6.11 µg/ml) resulted in higher drug concentrations in the AH when compared with intravitreal injection (0.42 ± 0.46 µg/ml, p = 0.001) 4 weeks after the treatment. The mean residence time last (MRT0-t ) by subretinal injection (11.57 ± 0.83 days) was significantly longer than the mean MRT0-t by intravitreal injection (7.10 ± 1.00 days, p < 0.001). A self-paired analysis showed that subretinal injection led to the BCVA improvement by +28.59 letters 6 months postoperatively (p = 0.028) while the BCVA did not improve significantly by intravitreal injection (p = 0.715). CONCLUSIONS: The drug maintenance phase was prolonged by intraoperative subretinal injection in SiO-filled eyes of PDR. The results suggest that subretinal injection might be a valuable treatment option for the management of PDR.

A modified intrascleral intraocular lens fixation technique with fewer anterior segment manipulations: 27-gauge needle-guided procedure with built-in 8-0 absorbable sutures.

BACKGROUND: To report a modified surgical technique for intrascleral intraocular lens (IOL) fixation with fewer anterior segment manipulations in eyes lacking sufficient capsular support. METHODS: Eyes from 14 patients who underwent 27-gauge needle-guided intrascleral IOL fixation with built-in 8-0 absorbable sutures were studied. The 8-0 absorbable sutures were inserted into 27-gauge round needles and used to create sclerotomies at the 4 o'clock and 10 o'clock positions under the scleral flap. The sutures were used to tie knots at the end of each haptic and guide haptic externalization through the sclerotomy. After externalization, a sufficient flange was created at the end of each haptic and fixed under the scleral flaps. The best corrected visual acuity (BCVA), corneal endothelial cell density (ECD), IOL tilt and decentration, previous surgery history, and complications were determined. RESULTS: Fourteen cases were analyzed. The majority of eyes exhibited an improvement in the BCVA after surgery. When comparing the last follow-up to preoperative visual acuity, the mean change in BCVA was + 26.32 letters (p = 0.011). Postoperative complications included postoperative hypotony in 3 eyes, ocular hypertension in 2 eyes. No cases of postoperative cystoid macular edema (CME), vitreous hemorrhage (VH), IOL dislocation, or endophthalmitis were observed. CONCLUSIONS: The 27-gauge needle-guided intrascleral IOL fixation technique with built-in 8-0 absorbable sutures is easy to perform with fewer anterior chamber manipulations and achieves both anatomical and optical stability.