Tae Yokoi

Vascular abnormalities in aggressive posterior retinopathy of prematurity detected by fluorescein angiography.

PURPOSE To evaluate fluorescein angiography (FA) in eyes with aggressive posterior retinopathy of prematurity (AP-ROP). DESIGN Retrospective, nonrandomized case series. PARTICIPANTS Three patients (6 eyes) with AP-ROP. METHODS Three patients (6 eyes) diagnosed with AP-ROP during ROP screening between July 2007 and July 2008 were included in this study. Fundus photographs and FA were obtained before and after laser and surgical treatment using a wide-field digital pediatric imaging system. MAIN OUTCOME MEASURES Fluorescein angiography and fundus photographs. RESULTS At the initial stage of AP-ROP, FA showed vascular abnormalities, including capillary nonperfusion throughout the vascularized retina, shunting in the vascularized retina, a circumferential demarcation line, and limited vessel development, which was difficult to identify only by ophthalmoscopy. After treatment, FA showed poorly developed retinal vessels, including 4 small major vessels without an arcade pattern, small macular vessels, an inhomogeneous capillary bed, and absence of a capillary-free zone in the fovea. CONCLUSIONS Capillary bed loss throughout the vascularized posterior retina is characteristic of AP-ROP and may exacerbate retinopathy.

Establishment of functioning human corneal endothelial cell line with high growth potential.

Hexagonal-shaped human corneal endothelial cells (HCEC) form a monolayer by adhering tightly through their intercellular adhesion molecules. Located at the posterior corneal surface, they maintain corneal translucency by dehydrating the corneal stroma, mainly through the Na+- and K+-dependent ATPase (Na+/K+-ATPase). Because HCEC proliferative activity is low in vivo, once HCEC are damaged and their numbers decrease, the cornea begins to show opacity due to overhydration, resulting in loss of vision. HCEC cell cycle arrest occurs at the G1 phase and is partly regulated by cyclin-dependent kinase inhibitors (CKIs) in the Rb pathway (p16-CDK4/CyclinD1-pRb). In this study, we tried to activate proliferation of HCEC by inhibiting CKIs. Retroviral transduction was used to generate two new HCEC lines: transduced human corneal endothelial cell by human papillomavirus type E6/E7 (THCEC (E6/E7)) and transduced human corneal endothelial cell by Cdk4R24C/CyclinD1 (THCEH (Cyclin)). Reverse transcriptase polymerase chain reaction analysis of gene expression revealed little difference between THCEC (E6/E7), THCEH (Cyclin) and non-transduced HCEC, but cell cycle-related genes were up-regulated in THCEC (E6/E7) and THCEH (Cyclin). THCEH (Cyclin) expressed intercellular molecules including ZO-1 and N-cadherin and showed similar Na+/K+-ATPase pump function to HCEC, which was not demonstrated in THCEC (E6/E7). This study shows that HCEC cell cycle activation can be achieved by inhibiting CKIs even while maintaining critical pump function and morphology.

Effect of Early Vitreous Surgery for Aggressive Posterior Retinopathy of Prematurity Detected by Fundus Fluorescein Angiography

OBJECTIVE To assess the effect of early vitrectomy for aggressive posterior retinopathy of prematurity (APROP) using fundus fluorescein angiography. DESIGN Retrospective, observational case series. PARTICIPANTS Eleven eyes of 7 patients with APROP that underwent early vitreous surgery. METHODS All eyes underwent vitrectomy with lensectomy that removed the vitreous gel around the fibrovascular proliferative tissue, but not the proliferative tissue when fibrovascular proliferation and retinal detachment occurred despite retinal photocoagulation. Fundus fluorescein angiography was performed before and after the early vitreous surgery. MAIN OUTCOME MEASURES Dye leakage from the fibrovascular tissue, dilation and tortuosity of the retinal vasculature, and shunt vessels were evaluated by fundus fluorescein angiography. The status of the retinal reattachment was assessed postoperatively. RESULTS Nine eyes had severe dye leakage from the fibrovascular tissue and 2 eyes had moderate leakage seen by preoperative fluorescein angiography. Severe dilation and tortuosity of the retinal vessels were detected in 10 eyes and shunt vessels in 7 eyes. Six to 12 days after successful surgery, the retina reattached and dilation and tortuosity of the retinal vessels decreased substantially. Dye leakage diminished markedly in all eyes, resolved completely in 7 eyes, and was still apparent slightly in 4. At the final examination, fibrovascular proliferation and retinal detachment did not progress in any eyes; however, 2 eyes had a dragged or folded retina. Follow-up ranged from 6 to 19 months (mean, 9.2). CONCLUSIONS Early vitrectomy that removes vitreous gel from around the proliferative tissue promptly reduces vascular activity and may limit progression of retinal detachment in APROP.

Peripapillary Diffuse Chorioretinal Atrophy in Children as a Sign of Eventual Pathologic Myopia in Adults

PURPOSE To search for a morphologic biomarker to differentiate between pathologic myopia and simple childhood myopia. DESIGN Retrospective case series. PARTICIPANTS The study included children (age ≤15 years) with high myopia (as defined by the Japanese Ministry of Health and Welfare) who attended the High Myopia Clinic between April 1982 and March 1994, had undergone fundus photography, and had a follow-up of 20 years or more. METHODS Fundus photographs obtained in childhood and adulthood were examined for presence of pathologic myopia, defined by high myopia (myopic refractive error >8 diopters or axial length ≥26.5 mm) and the presence of stage 2 or higher myopic maculopathy. MAIN OUTCOME MEASURES Myopic maculopathy in childhood. RESULTS The study included 56 eyes of 29 patients with a mean age of 10.2±3.6 years at the initial visit and an age of 36.0±7.6 years at the last visit. Mean axial length was 27.0±1.4 mm at baseline and 29.7±2.0 mm at the last visit. At the last visit, 19 eyes (34%) had tessellated fundus alone, 31 eyes (55%) had diffuse chorioretinal atrophy, 3 eyes (5%) showed patchy chorioretinal atrophy, and 1 eye (2%) had macular atrophy. Thus, 35 eyes (63%) had pathologic myopia in adulthood. Among the 35 eyes, 29 (83%) already had diffuse chorioretinal atrophy at the initial visit in childhood and the remaining 6 eyes (17%) showed tessellated fundus in childhood. The diffuse chorioretinal atrophy seen in childhood was restricted to the area temporal to the peripapillary region. CONCLUSIONS The presence of peripapillary diffuse chorioretinal atrophy in children with high axial myopia may be an indicator for the eventual development of advanced myopic chorioretinal atrophy in later life. These features in children may be helpful for differentiating simple childhood myopia from eventual pathologic myopia.

SIX-YEAR OUTCOMES OF INTRAVITREAL BEVACIZUMAB FOR CHOROIDAL NEOVASCULARIZATION IN PATIENTS WITH PATHOLOGIC MYOPIA.

Purpose: To investigate the 6-year outcome of intravitreal bevacizumab (IVB) to treat eyes with active choroidal neovascularization (CNV) due to pathologic myopia. Methods: Medical records of 36 eyes of 35 consecutive patients with high myopia (refractive error ≥8 D or axial length ≥26.5 mm) and active CNV, who had been treated with IVB and followed for ≥6 years were analyzed. The factors that predicted the best-corrected visual acuity (BCVA) at 6 years after IVB were determined by multiple regression analyses. Results: The mean age of the subjects was 58 years, and the mean axial length was 29 mm. Twenty-one eyes had subfoveal CNV and 15 eyes had nonsubfoveal CNV. During the 6-year follow-up, the mean number of IVB was 1.78. The mean BCVA logMAR (equivalent Snellen visual acuity) was 0.50 (20/63), 0.31 (20/40), 0.39 (20/50), and 0.45 (20/63) at the baseline, and at 2, 4, and 6 years after the IVB. The BCVA was significantly improved at 2 and 4 years compared with baseline values but not at 6 years. Stepwise multiple regression analyses showed that the BVCA at 6 years was significantly correlated with the size of the CNV-related macular atrophy, and the baseline BCVA and CNV size. Conclusion: The significant correlation between the BCVA at 6 years and the size of the macular atrophy indicates that treatments to prevent the development of macular atrophy are important for the long-term visual outcome in eyes with active CNV.

Risk Factors for Recurrent Fibrovascular Proliferation in Aggressive Posterior Retinopathy of Prematurity After Early Vitreous Surgery

PURPOSE To analyze risk factors for postoperative recurrence of fibrovascular tissue in eyes with aggressive posterior retinopathy of prematurity (AP ROP) treated with early vitreous surgery. DESIGN Retrospective, consecutive, observational case series. METHODS Thirty-one patients (50 eyes) with AP ROP who underwent early vitreous surgery between March 2005 and April 2008 participated. Eyes with stage 4A or 4B disease in which fibrovascular tissue was not attached to the vitreous base were included; those in which fibrovascular tissue was attached extensively to vitreous base or those without dense photocoagulation to the nonvascularized retina were excluded. Eligible eyes were divided into 2 groups based on postoperative recurrence or no recurrence of fibrovascular tissue. Data on gender, gestational age, birth weight, Apgar score, intubation duration, severe systemic complications, preoperative ROP stage, zone, fibrovascular tissue and vitreous base adhesion, clock hours of fibrovascular tissue, postmenstrual age at the initial application of dense photocoagulation, dense photocoagulation to both vascularized and nonvascularized retina, postmenstrual age at vitrectomy, and intraoperative hemorrhage were collected and analyzed. RESULTS Fifty eyes of 31 patients underwent early vitrectomy. Seven (14%) eyes were excluded and 43 eyes (86%) were included. Eight (18%) of 43 eyes had a recurrence of fibrovascular tissue. Both univariate and multivariate analysis indicated application of dense photocoagulation to both the vascularized and nonvascularized retina was a significant factor in the decreased recurrence of fibrovascular tissue (P = .002 and P = .008, respectively). CONCLUSIONS Application of preoperative dense photocoagulation to vascularized and nonvascularized retina may be important for lowering the recurrence of fibrovascular tissue in eyes with AP ROP.

Evaluation of scleral buckling for stage 4A retinopathy of prematurity by fluorescein angiography.

PURPOSE To determine the early efficacy of scleral buckling for active neovascularization by fundus fluorescein angiography (FA) in eyes with stage 4A retinopathy of prematurity. DESIGN A retrospective, nonrandomized, observational case series. METHODS Patients who underwent scleral buckling for stage 4A ROP at the National Center for Child Health and Development, Tokyo, Japan, from October 2007 through November 2008 were included. Preoperative and postoperative FA and fundus photographs obtained with a wide-field digital pediatric imaging system were reviewed. Three patients (5 eyes; gestational ages at birth, 23 to 25 weeks; birth weights, 574 to 811 g) with zone II stage 4A ROP who underwent postoperative FA, 2 weeks or less after scleral buckling (range, 7 to 12 days; postmenstrual ages at postoperative FA, 41 to 45 weeks) were evaluated. Patients who underwent postoperative FA 2 weeks or more after scleral buckling were excluded. RESULTS Despite fluorescein leakage from fibrovascular tissue in all eyes before surgery, markedly decreased leakage occurred only between 7 to 12 days after surgery. The retinas were reattached completely in all eyes after surgery. CONCLUSIONS Scleral buckling may prevent progression of retinal detachment in stage 4A ROP by reducing the tractional force and stabilizing the neovascular activity of the fibrovascular tissue.

Fluorescein staining of the vitreous during vitrectomy for retinopathy of prematurity.

V itreous staining using triamcinolone acetonide 1 or fluorescein generally has been used even in children to visualize the preretinal membrane and vitreous during vitrectomy. During the surgery for retinopathy of prematurity (ROP), careful segmentation and extensive vitreous cutting are required around the base of tractional retinal detachments, vitreous base, and fibrovascular tissue. Removal of the formed vitreous around the fibrovascular tissue and the vitreous base is a key factor for a successful surgery. To remove the vitreous safely, good intraoperative visualization of the vitreous is essential. In the current study, we included cases of aggressive posterior ROP in which wide-field vitrectomies are necessary to evaluate the staining of the entire vitreous. We describe a technique for staining the vitreous with fluorescein and compared it with staining using triamcinolone in these patients with ROP.

Macular Bruch's Membrane Defect and Dome-Shaped Macula in High Myopia

Purpose To examine an association between macular Bruch’s membrane defects (MBMD) and a dome-shaped appearance of the macula (DSM). Design Retrospective, observational case series study. Methods The study included highly myopic individuals who were consecutively examined between May 2014 and December 2015. The patients underwent swept-source optical coherence tomography (OCT) for visualization of DSM and MBMDs defined as Bruch´s membrane defects located at a distance of maximal 1500 μm from the foveola. Results Out of 1983 highly myopic eyes (1057 patients), 166 eyes (8.4%; 95% confidence interval (CI):7.2%,9.6%)) showed a DSM and 534 eyes showed a MBMD. In multivariate binary regression analysis, higher prevalence of DSM was associated with a higher prevalence of a MBMD (P<0.001; OR: 1.96; 95%CI: 1.40, 2.75) after adjusting for longer axial length (P<0.001; odds ratio (OR): 1.27; 95%CI: 1.16, 1.38). In eyes with a DSM partially surrounded by a MBMD, the retina, retinal pigment epithelium (RPE) and choroid appeared relatively unchanged in the central region with Bruch´s membrane (BM) preserved. In the ring-like BM-free region surrounding the central prominent island of the DSM, the RPE, the outer and middle retinal layers, the choriocapillaris and the middle-sized choroidal vessel layer were absent. In association with a DSM, three MBMD types were differentiated: MBMDs in patchy chorioretinal atrophy, MBMDs in choroidal neovascularization-related macular atrophy, and MBMDs as temporally extending large parapapillary gamma zone. Conclusions Presence of a DSM was significantly associated with the presence of MBMDs. The morphology of the DSM in association with MBMDs may be associated with a focal relaxation of the posterior sclera, no longer pushed outward by an expanding BM but allowed to partially bulge inward, leading to the formation of a DSM.

Parapapillary Diffuse Choroidal Atrophy in Children Is Associated With Extreme Thinning of Parapapillary ChoroidParapapillary Diffuse Choroidal Atrophy in Children

Purpose To analyze morphologic features of segmental parapapillary diffuse choroidal atrophy (PDCA) in children. Methods The study group included children (age ≤15 years) with high myopia who attended the Tokyo High Myopia Clinic. Control groups comprised participants of the population-based Gobi Desert Children Eye Study (GobiDCES). Fundus photographs were examined for presence of PDCA and choroidal thickness (CT) was measured by optical coherence tomography. Results The study group included 41 eyes of 21 children with PDCA (mean age: 9.4 ± 3.7 years; mean refractive error: -11.5 ± 3.1 diopters) and the GobiDCES included 1463 children (age: 11.8 ± 3.5 years). In the study group, all eyes showed an extreme and abrupt thinning of the temporal parapapillary choroid. At 2500 μm nasal to the foveola, CT was <60 μm in 31 (76%) eyes of the study group but in none (0/1463) of the GobiDCES (P < 0.001), except for one child with PDCA. Conclusions Parapapillary diffuse choroidal atrophy in children is associated with abrupt segmental thinning of the choroid in the temporal parapapillary region, in addition to the thinning of the subfoveal choroid after adjusting for refractive error and age.