Yosuke Sugimoto

Craniosynostosis in a patient with a de novo 15q15-q22 deletion†

Interstitial deletions involving the chromosomal band 15q15 are very rare. A total of five cases were previously reported. Here another case of a 15q15.2‐q22.2 deletion is reported, presenting with severe craniosynostosis of coronary, metopic, and sagittal sutures. The chromosome 15 with the 17.7‐Mb deletion was of the paternal origin. A critical region for craniosynostosis may be located at the 734‐kb segment at 15q15.2. Interestingly, the entire FBN1 gene was deleted in this patient.

Comparison of the prevalence of plateau iris configurations between angle-closure glaucoma and open-angle glaucoma using ultrasound biomicroscopy.

PurposeTo determine the prevalence of plateau iris configurations in acute primary angle-closure (APAC), chronic angle-closure glaucoma (CACG), and open-angle glaucoma (OAG) eyes using ultrasound biomicroscopy. Materials and MethodsThe study included fellow eyes of 27 APAC patients, 26 OAG patients, and 26 CACG patients with no history of APAC. Patients with a history of earlier intraocular surgery or argon laser peripheral iridoplasty were excluded from the study. Eyes that had not undergone laser peripheral iridotomy were excluded from APAC and CACG groups. Radial scans were carried out using ultrasound biomicroscopy in all 4 quadrants. A plateau iris configuration within a quadrant was defined by the presence of an anteriorly positioned ciliary process, a narrow ciliary sulcus, a steeply rising peripheral iris, followed by a downward angulation from the corneoscleral wall and the presence of a flat iris plane. Eyes with plateau iris configurations were defined as those having at least 2 quadrants fulfilling these criteria. ResultsPlateau iris configurations were found in fellow eyes of 10 of 27 patients with (37.0%) APAC, 9 of 26 (34.6%) patients with CACG, and 5 of 26 (19.2%) patients with OAG. No significant difference in the prevalence of plateau iris configurations was observed among the 3 groups (P=0.314, &khgr;2 test). ConclusionsEyes with OAG had a higher rate of plateau iris configurations than expected. Longitudinal studies to evaluate plateau iris height are required to determine its significance in the pathogenesis of angle-closure glaucoma.

Intraocular Pressure Outcomes and Risk Factors for Failure in the Collaborative Bleb-Related Infection Incidence and Treatment Study

PURPOSE To evaluate the efficacy and safety of trabeculectomy for patients with glaucoma who were enrolled in the Collaborative Bleb-related Infection Incidence and Treatment Study (CBIITS). DESIGN Multicenter, prospective, cohort study. PARTICIPANTS A total of 829 eyes in 829 patients with glaucoma who had undergone trabeculectomy alone or trabeculectomy combined with phacoemulsification at 34 clinical centers were examined in this study. MAIN OUTCOME MEASURES Intraocular pressures (IOPs, in millimeters of mercury), risk factors for surgical failure, and surgical complications. METHODS The enrollment period was 2 years, and follow-up was conducted every 6 months for up to 5 years. Outcomes were measured at 6-month intervals. Four levels of success were defined by achievement of the following IOP: (A) 4<IOP<22, (B) 4<IOP<19, (C) 4<IOP<16, and (D) 4<IOP<13. The primary outcome was the qualified success rate according to the defined criteria. The secondary outcomes included IOP, risk factors for surgical failure, and surgical complications. RESULTS Mean IOP and preoperative antiglaucoma medications were significantly decreased from 24.9±9.0 to 12.6±5.2 mmHg (P<0.0001) and from 2.8±1.0 to 1.2±1.3 mmHg (P<0.0001), respectively, 5 years after surgery. For criteria A, B, C, and D, the qualified success rates were 90.1%, 88.9%, 77.6%, and 57.7% at 1 year, respectively, and 71.9%, 66.7%, 50.1%, and 29.9% at 5 years, respectively. The third or subsequent trabeculectomy was less effective than the first and second trabeculectomies. Preoperative lens status and preoperative higher IOP were risk factors for trabeculectomy failure. The needling procedure and cataract surgery were associated with the risk of failure. The rates of postoperative hyphema, shallow anterior chamber, bleb leak, and choroidal detachment were 2.7%, 3.1%, 1.9%, and 7.2%, respectively, in our series. CONCLUSIONS Trabeculectomy with mitomycin C is an effective and safe procedure for reducing IOP in the CBIITS. The number of previous glaucoma surgeries, preoperative lens status and IOP, the needling procedure, and cataract surgery after trabeculectomy influenced the success rate, as determined by the target IOP.

Histological findings of uveal capillaries in rabbit eyes after multiple intravitreal injections of bevacizumab

Abstract Purpose: To evaluate the potential toxicity of multiple intravitreal injections of bevacizumab on the uveal capillaries of rabbit eyes. Materials and methods: Nine eyes of nine rabbits that received single intravitreal injections of bevacizumab (IVB) constituted the single IVB group, while nine eyes of nine rabbits that received three injections of IVB, with an interval of 28 days between injections, constituted the repeat IVB group. Seven eyes of seven rabbits constituted the control group. The rabbits in the single and repeat IVB groups were sacrificed 7 and 28 d after the single and third IVB injection, respectively. Uveal specimens were compared between groups after immunohistochemical staining. Ultrastructural findings were evaluated by electron microscopy. Control group rabbits were sacrificed 7 d after saline injection. Clinical examination and fundus fluorescein angiography were performed at baseline, 7 d after the first injection, and after the last injection. Results: Differences in the CD31-positive areas of the iris, ciliary body and choroid 7 d after IVB were not statistically significant among the single IVB, repeat IVB and control groups (p = 0.0749, p = 0.7237 and p = 0.7346, respectively; analysis of variance). Endothelial cell fenestrations (ECFs) in the choriocapillaris and ciliary body observed by electron microscopy on day 7 in the single and repeat IVB groups were decreased by 50% (p < 0.0001) and 33% (p < 0.0001), respectively, in both IVB groups compared with those in the control group. However, ECFs observed on day 28 in both groups were comparable to those observed in the control group. Conclusions: Single IVB and repeated IVB did not have any effect on normal vessel endothelium density as per immunohistochemical findings. Ultrastructural findings revealed that IVB transiently decreased the ECFs in the choriocapillaris and ciliary body.

The signs of ocular-surface disorders after switching from latanoprost to tafluprost/timolol fixed combination: a prospective study

Purpose To evaluate the ocular-surface safety of a 0.001% benzalkonium chloride-containing tafluprost/timolol fixed combination (TTFC) in patients with primary open-angle glaucoma (POAG) or ocular hypertension who have inadequate intraocular pressure (IOP) control with latanoprost monotherapy. Methods This study is a multicenter, prospective, single-arm, open-label clinical study. Patients with POAG or ocular hypertension who have inadequate IOP control with latanoprost monotherapy were considered eligible. After providing informed consent, patients continued latanoprost monotherapy for 12 weeks, followed by a switch to TTFC. We evaluated the extent of ocular-surface damage using superficial punctate keratopathy (SPK) score, tear breakup time (TBUT), hyperemia score, IOP, systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate at 0, 4, and 12 weeks after switching. Results A total of 68 patients were enrolled, of whom, 64 patients were included in the final analysis. No significant changes in SPK score, TBUT, or hyperemia score were observed at 4 and 12 weeks compared with week 0. IOP decreased significantly at 4 (13.9±2.5 mmHg) and 12 (14.1±2.5 mmHg) weeks, relative to week 0 (15.3±2.7 mmHg). No significant changes in either SBP or DBP were observed during the study, although patients’ mean heart rate decreased significantly after switching to TTFC. Adverse drug reactions to TTFC occurred in seven patients including two incidences of asthma and one of arrhythmia, and no events were serious. Conclusion The ocular-surface safety of TTFC is not significantly different to that of latanoprost. Furthermore, switching from latanoprost to TTFC in patients with insufficient IOP control has additive IOP-lowering effects. TTFC is an effective approach for patients receiving latanoprost monotherapy who require more intensive IOP reduction.

Down-regulation of semaphorin 3F in rat retinal ganglion cells in response to optic nerve crush.

Glaucoma is characterized by degeneration of optic nerve axons and death of retinal ganglion cells (RGCs). Nerve crush and axotomy of the optic nerve are studied as models of RGC death in glaucoma and of axon regeneration. The mechanisms underlying the response of RGCs to axonal injury remain unclear, however. We have now examined the effects of optic nerve crush on the expression of members of the semaphorin family of neuronal guidance proteins in the rat retina. The expression of semaphorin 3F (Sema3F) in the retina was down‐regulated at both the mRNA and protein levels at 7 days after optic nerve injury, whereas that of Sema3A, Sema3B or Sema3C remained unaffected. Immunohistofluorescence analysis and laser capture microdissection followed by reverse transcription–polymerase chain reaction analysis revealed that this loss of Sema3F expression occurred in the RGC layer of the retina. Furthermore, antibody‐mediated neutralization of secreted Sema3F in retinal organ culture resulted in down‐regulation of neuron‐specific βIII‐tubulin (Tuj‐1 antigen), a marker of RGCs. Our results suggest that Sema3F may contribute to the regulation of RGC function or survival and therefore warrants further investigation as a potential mediator of neuroprotection. Copyright