Satoshi Okinami

Long-term outcomes and prognostic factors for trabeculectomy with mitomycin C in eyes with uveitic glaucoma: a retrospective cohort study.

Purpose:To elucidate the long-term outcomes and prognostic factors for trabeculectomy with mitomycin C (MMC) in eyes with uveitic glaucoma (UG). Methods:A retrospective, consecutive, comparative cohort study was conducted with 204 patients who underwent trabeculectomy with MMC between 1999 and 2008 at 2 Japanese clinical centers. The study group included 101 eyes with UG and 103 eyes with primary open-angle glaucoma (POAG). Surgical failure was defined as intraocular pressure levels of ≥21 mm Hg or an additional glaucoma surgery. Kaplan-Meier survival curves for surgical failure were compared between UG and POAG eyes, and prognostic factors for surgical failure of trabeculectomy in UG eyes were analyzed by the Cox proportional hazards model. Secondary outcome measures included comparisons of the frequency of additional cataract surgery and other surgical complications after trabeculectomy between UG and POAG eyes. Results:The mean follow-up periods (±SD) were 34.7±37.9 and 37.7±34.7 months (median, 24.0 and 27.4 mo) for UG and POAG, respectively. The subtypes of uveitis were granulomatous uveitis (n=20) including sarcoidosis (n=12), Vogt-Koyanagi-Harada disease (n=5) and varicella zoster virus uveitis (n=3), Behçet disease (n=10), Posner-Schlossman syndrome (n=5), and other types of UG (n=12). Fifty-four eyes were diagnosed with idiopathic UG. The 3-year probabilities of success after trabeculectomy were 71.3% and 89.7% for UG and POAG, respectively (P=0.0171). A multivariable model showed that UG eyes with previous cataract surgery [relative risk (RR)=2.957, P=0.0344)] and granulomatous uveitis (RR=3.805, P=0.0106) were associated with surgical failure. UG eyes experienced more frequent cataract surgeries after trabeculectomy than POAG eyes: the 3-year probabilities of additional cataract surgery of 62.6% and 10.7% for UG and POAG, respectively (P<0.0001). There was no significant difference in the frequency of surgical complications such as bleb leakage, hypotensive maculopathy, severe anterior-chamber hemorrhage, and infectious endophthalmitis. Conclusions:Trabeculectomy with MMC was less effective in maintaining intraocular pressure reduction in UG eyes than in POAG eyes. The prognostic factors for surgical failure of trabeculectomy in UG eyes were previous cataract surgery and granulomatous uveitis. In addition, UG eyes after trabeculectomy more frequently required additional cataract surgery.

Heparan sulfate deficiency leads to Peters anomaly in mice by disturbing neural crest TGF-β2 signaling

During human embryogenesis, neural crest cells migrate to the anterior chamber of the eye and then differentiate into the inner layers of the cornea, the iridocorneal angle, and the anterior portion of the iris. When proper development does not occur, this causes iridocorneal angle dysgenesis and intraocular pressure (IOP) elevation, which ultimately results in developmental glaucoma. Here, we show that heparan sulfate (HS) deficiency in mouse neural crest cells causes anterior chamber dysgenesis, including corneal endothelium defects, corneal stroma hypoplasia, and iridocorneal angle dysgenesis. These dysfunctions are phenotypes of the human developmental glaucoma, Peters anomaly. In the neural crest cells of mice embryos, disruption of the gene encoding exostosin 1 (Ext1), which is an indispensable enzyme for HS synthesis, resulted in disturbed TGF-beta2 signaling. This led to reduced phosphorylation of Smad2 and downregulated expression of forkhead box C1 (Foxc1) and paired-like homeodomain transcription factor 2 (Pitx2), transcription factors that have been identified as the causative genes for developmental glaucoma. Furthermore, impaired interactions between HS and TGF-beta2 induced developmental glaucoma, which was manifested as an IOP elevation caused by iridocorneal angle dysgenesis. These findings suggest that HS is necessary for neural crest cells to form the anterior chamber via TGF-beta2 signaling. Disturbances of HS synthesis might therefore contribute to the pathology of developmental glaucoma.

Expression of estrogen receptor in the choroidal neovascular membranes in highly myopic eyes.

Purpose To investigate the expression of estrogen receptor in choroidal neovascular membranes (CNVMs) surgically excised from eyes with high myopia. Methods The CNVMs were surgically excised from two eyes with high myopia. Immunohistochemical analysis with a monoclonal antibody to estrogen receptor and in situ hybridization with an oligodeoxynucleotide sequence coding for estrogen receptor were used to study the cellular distribution of estrogen receptor and its messenger RNA in the CNVMs. Immunohistochemical localization of glial fibrillary acidic protein and vimentin in the CNVMs was compared with localization of estrogen receptor. Results Immunohistochemical analysis with monoclonal antibody to estrogen receptor showed widespread staining throughout the CNVMs. By in situ hybridization, the expression of estrogen receptor messenger RNA was predominantly observed in the CNVMs. Staining with antibody to vimentin was widespread throughout the CNVMs, which was similar to the localization of estrogen receptor. Conclusion Estrogen receptor was expressed in the CNVMs in highly myopic eyes, suggesting that estrogen may have important functions in the formation of CNVMs.

A comparison of intraocular pressure-lowering effect of prostaglandin F2 -alpha analogues, latanoprost, and unoprostone isopropyl.

PurposeTo compare the intraocular pressure-lowering effect of unoprostone isopropyl (unoprostone) 0.12% and latanoprost 0.005%. A correlation between the intraocular pressure-lowering effect of unoprostone and latanoprost was also evaluated. MethodsA single-masked randomized study included 18 patients between 49 and 68 years (mean, 60.7 ± 5.1 years) with an intraocular pressure of both eyes from 21 to 27 mm Hg. The patients were prospectively randomized to receive latanoprost in the right eye and unoprostone in the left eye, or unoprostone in the right eye and latanoprost in the left eye. The patients were followed up for 8 weeks. This study evaluated the intraocular pressure-lowering effect and incidence of drug-related side effects. ResultsMean baseline intraocular pressure was 22.8 ± 1.2 mm Hg in latanoprost-treated eyes and 22.4 ± 1.0 mm Hg in unoprostone-treated eyes; there was no statistically significant difference between these groups. Mean intraocular pressure at 8 weeks after the start of the administration was 16.7 ± 2.0 mm Hg in latanoprost-treated eyes and 19.0 ± 1.5 mm Hg in unoprostone-treated eyes. Patients in the latanoprost-treated group showed a greater intraocular pressure reduction compared with those in the unoprostone-treated group. Mean intraocular pressure changes in latanoprost-treated eyes were significantly greater at every visit (P < 0.0001). A change of intraocular pressure at 8 weeks in the latanoprost-treated eyes was significantly correlated with that in the contralateral unoprostone-treated eyes (r = 0.665, P = 0.0013) (Figure). There was no significant difference in the rate of ocular side effects between latanoprost- and unoprostone-treated eyes. ConclusionsLatanoprost appears to have a more beneficial effect for intraocular pressure control compared with unoprostone. An intraocular pressure reduction in the latanoprost-treated eyes was significantly correlated with that in the contralateral unoprostone-treated eyes. There was no significant difference in the incidence of ocular side effects between both drugs. Further investigation using more cases and longer follow-up periods are needed.

Protein-losing gastroenteropathy and retinitis associated with cytomegalovirus infection in an immunocompetent infant: a case report

A 6-week-old immunocompetent girl developed protein-losing gastroenteropathy (PLGE) and retinitis associated with cytomegalovirus (CMV) infection. At presentation, CMV antigenaemia (6 cells/46,000 white blood cells) and its DNA were detected in the patient’s blood and in the mother’s milk. Intravenous ganciclovir and γ-globulin rapidly ameliorated all symptoms and CMV antigenaemia disappeared. No immunological defects were identified in this patient. To the best of our knowledge, this case involves the youngest known immunocompetent patient demonstrating CMV-induced PLGE and retinitis. Conclusion:breast-feeding by a cytomegalovirus-positive mother can be a primary cause of early onset cytomegalovirus infection in infants.

Freeze-fracture replica of the primate lens fibers

Using freeze-fracture techniques, we studied the fine structure of monkey lens fibers, with special reference to intercellular junctions. Gap junctions were frequently observed at the ‘ball- and-socket’ interdigitations, the ‘tongue- and-groove’ interdigitations, and between cortical lens fibers, while tight junctions were never apparent.

Efficacy of bunazosin hydrochloride 0.01% as adjunctive therapy of latanoprost or timolol

PurposeTo evaluate the ocular hypotensive response of bunazosin hydrochloride 0.01% administered as adjunctive therapy in patients with glaucoma who were already receiving latanoprost 0.005% or timolol 0.5%. MethodsPatients with primary open angle glaucoma who had received latanoprost (n = 60) or timolol (n = 60) for 6 months or longer were enrolled and prospectively randomized to receive additional administration of bunazosin or placebo. One hundred twenty eyes of 120 patients were thus divided into 4 subgroups of 30 patients each. Bunazosin was administered twice daily, and timolol or latanoprost was administered per label. The patients were followed up for 3 months. Responders were defined as having a reduction in intraocular pressure of greater than 2 mm Hg from baseline. ResultsMean baseline intraocular pressure was 22.3 ± 3.0 mm Hg in the bunazosin subgroup and 22.3 ± 3.1 mm Hg in the placebo subgroup of the latanoprost arm, and 22.5 ± 3.5 mm Hg in the bunazosin subgroup and 22.3 ± 3.0 mm Hg in the placebo subgroup of the timolol arm. In the bunazosin subgroups of both arms, intraocular pressure was significantly reduced compared with baseline measurements (P < 0.05) with mean intraocular pressure measurement reductions of 2.1 ± 2.4 mm Hg and 2.8 ± 2.1 mm Hg in the latanoprost arm and 2.6 ± 2.1 mm Hg and 2.8 ± 2.1 mm Hg in the timolol arm at 6 and 12 weeks after the start of the follow-up, respectively. In the latanoprost group, bunazosin provided a further reduction of intraocular pressure (7.7%) at 12 weeks from that initially obtained at 2 weeks (P = 0.0377). In the placebo subgroups of the latanoprost and timolol arms, no significant change was found between at baseline and at any visit after the start of the follow-up. In the latanoprost and timolol arms, there was a significant difference in intraocular pressure and its change between the bunazosin subgroup and placebo subgroup at any visit after 4 weeks from the start of the follow-up (P < 0.01). ConclusionBunazosin hydrochloride 0.01% may provide an additional intraocular pressure reduction in patients already receiving latanoprost or timolol. Since adding bunazosin to eyes treated with latanoprost caused a relatively small hypotensive response at 2 weeks and provided a further reduction from 2 weeks to 12 weeks, longer than 4 weeks may be required to evaluate a clinically meaningful response to treatment. Further investigation on more cases and longer follow-up are needed.

Fate mapping of neural crest cells during eye development using a protein 0 promoter-driven transgenic technique.

PurposeTo map neural crest cell fate during eye development.MethodsNeural crest cells were tracked in developing mouse eyes using a transgene expressing Cre recombinase controlled by the Protein 0 promoter and a Rosa26 Cre-responsive reporter gene that produced β-galactosidase after Cre-mediated recombination.Resultsβ-galactosidase-positive cells were detected in the periocular segment on embryonic day (E) 9.5. Several neural crest cell-derived tissues including corneal stroma, corneal endothelium, iridocorneal angle, ciliary body, primary vitreous and eyelid were strongly stained on E13.5–E18.5. The staining decreased in the corneal stroma after birth, but persisted in the presumptive iridocorneal angle.ConclusionsProtein 0-Cre transgenic mice offer a conditional knock-out strategy to investigate anterior eye segment differentiation.

Neuroprotective effect of small interfering RNA targeted to caspase-3 on rat retinal ganglion cell loss induced by ischemia and reperfusion injury.

Purpose: To investigate neuroprotective effects of siRNA targeted to caspase-3 against ischemia and reperfusion (I/R) injury in rat eyes. Methods: Retinal ischemia was induced in Wistar rats by increasing the intraocular pressure (IOP) to 110 mmHg for 120 min. To examine the effect of siRNA on rat caspase-3, siRNA was injected into the vitreous cavity 24 h prior to induction of retinal ischemia. Eyes were removed at 2, 7 or 14 days later, and then analyzed for the number of retinal ganglion cells (RGCs), the retinal thickness and the amount of apoptosis of the retinal neural cells (as demonstrated by the TUNEL assay). The amount of caspase-3 mRNA was analyzed by rt-PCR. Differences between groups were evaluated by an unpaired t test. Results: The numbers of RGCs in the saline and non-silencing siRNA controls were reduced significantly at 2 and 7 days after the I/R injury. RGCs were significantly retained in eyes pretreated with siRNA targeted to caspase-3 as compared to the control eyes at 2 days after the I/R injury. Inner retinal thickness in the control eyes was significantly thinner as compared to the treated eyes at 2 and 7 days after the I/R injury. After siRNA treatment, the amount of caspase-3 mRNA was significantly lower when compared to the saline control group. Conclusions: The injection of siRNA targeted to caspase-3 into the vitreous cavity of rat eyes may block caspase-3, and may thus be able to prevent retinal cell death associated with ischemic injury. As inhibition of the apoptosis pathway may provide a neuroprotective effect, examination of new strategies for treating these disorders needs to be undertaken.

Occurrence of capsular delamination in the dislocated in-the-bag intraocular lens

PurposeTo examine the lens capsules of dislocated in-the-bag IOLs.MethodsRetrospective case series. Nineteen dislocated IOLs encased in capsules (in-the-bag IOLs) from 19 patients were included. The clinical characteristics of the 19 patients were reviewed. The explanted in-the- bag IOLs were examined by scanning electron microscopy.ResultsAssociated clinical conditions included pseudoexfoliation (PEX) in seven eyes, high myopia in three eyes, previous history of trauma in two eyes, previous vitreoretinal surgery in two eyes, retinitis pigmentosa in one eye and uveitis in one eye. PEX specimens showed capsular contraction, shrinkage of the diameter of the capsular bag and dehiscence of zonular fibers. The remaining 12 specimens exhibited slight capsular contraction that lacked shrinkage of the bag and exhibited capsular delamination at the equatorial region, in which the zonular fibers had completely disappeared.ConclusionCapsular delamination as well as dehiscence of zonular fibers may be involved in the dislocation of in-the-bag IOLs.