High-Temperature Requirement A 1 Causes Photoreceptor Cell Death in Zebrafish Disease Models.

Age-related macular degeneration (AMD) is an important cause of blindness. It is characterized by a retinal pigment epithelium (RPE) disorder that leads to death of photoreceptor cells (PRCs). AMD has a strong genetic association with high-temperature requirement A 1 (HTRA1). The relationship between HTRA1 and the AMD phenotype is unknown. In this study, we show that the expression of HTRA1 in PRCs, as well as in RPE, is increased by the disease-associated HTRA1 mutation and aging. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay and quantitative PCR of apoptosis-associated caspases confirmed that PRC-specific overexpression of HTRA1 induced PRC death. Transgenic zebrafish overexpressing human HTRA1 in rod PRCs showed morphologic changes of the RPE, including PRC death and lipofuscin accumulation, features similar to those of early AMD. htra1 expression was also increased in a retinitis pigmentosa zebrafish model compared with wild type. In both fish lines, PRC death was rescued by the suppression of htra1 by the inhibitor 6-boroV. AKT-forkhead box O3 signaling downstream of HTRA1 was activated via a tumor growth factor ß signal, resulting in PRC death. These findings suggest that HTRA1 derived from PRCs is associated with early AMD via PRC death. HTRA1 is a potentially effective target for neuroprotective therapy of early AMD and other degenerative diseases of PRCs.

[Efficacy of intravitreal bevacizumab for age-related macular degeneration].

PURPOSE: To investigate the efficacy of intravitreal bevacizumab (IVB) for neovascular age-related macular degeneration (AMD). METHODS: We conducted a retrospective study of 29 eyes of 29 patients with AMD (19 eyes) and polypoidal choroidal vasculopathy (PCV; 10 eyes), who were followed up at least 1 year after the initial IVB (1.0 mg/0.04 ml). The eyes were classified according to the lesion type and size. Best-corrected visual acuity (BCVA) and central retinal thickness were examined before and 3 months, 6 months and 12 months after the IVB. RESULTS: The mean application times of IVB were 2.1 in 1 year. When classifying the eyes according to the lesion type, BCVA improved in 5 (26.3%) eyes with AMD and 1 (10.0%) eye with PCV by over 0.2 logarithmic minimum angle of resolution (logMAR) units. The BCVA decreased significantly 1 year after the IVB in eyes with PCV (p = 0.032). When classifying the eyes according to the lesion size, BCVA improved by over 0.2 logMAR units in the 4 (50.0%) eyes with a size of less than 1 disc diameter, 1 (10.0%) eye with the size of 1 to 3 disc diameters, and 1 (9.1%) eye with the size of over 4 disc diameters. The BCVA decreased significantly 1 year after the IVB in the eyes with the size of 1 to 3 disc diameters and with the size of over 4 disc diameters (p = 0.028, 0.013, respectively). The central retinal thickness did not change significantly at any time point compared to that before the IVB. CONCLUSIONS: These results suggest that IVB may be efficacious in preserving visual acuity in AMD eyes and in eyes with the size of less than 1 disc diameter.

[Efficacy of treatments on vision-related quality of life in patients with diabetic retinopathy].

PURPOSE: To evaluate changes in the vision-related quality of life in patients with diabetic retinopathy with the 25-item National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25). Patients were categorized into three groups : without treatment, receiving pan-retinal photocoagulation, and those who had vitrectomy. SUBJECTS AND METHODS: Altogether 327 patients (131 without treatment, [observation group]; 60 receiving pan-retinal photocoagulation, [photocoagulation group]; and 136 patients who had vitrectomy, [vitrectomy group]). The VFQ-25 was recorded at the time of entry and 1 year later. The VFQ-25 score was compared between the time of entry and 1 year later for each group and among the three groups at both the time of entry and 1 year later. RESULTS: VFQ-25 scores (mean +/- standard deviations) at the time of entry and 1 year later were 91.3 +/- 7.8 and 92.2 +/- 7.8 in the observation group, 80.7 +/- 15.7 and 77.6 +/-19.1 in the photocoagulation group, and 67.4 +/-17.3 and 75.4 +/- 17.5 in the vitrectomy group. VFQ-25 scores in the observation group and in the photocoagulation group did not change statistically between the time of entry and 1 year later (p = 0.113, 0.169, respectively), while the score of the vitrectomy group increased statistically (p < 0.001). In addition, although VFQ-25 scores were statistically significant among the three groups at the time of entry (p < 0.05), the scores 1 year later were not statistically different between the photocoagulation group and vitrectomy group. CONCLUSIONS: These results suggest that vitrectomy for diabetic retinopathy may be effective in increasing the quality of life of patients with diabetic retinopathy.

Cross-Sectional Imaging Analysis of Epiretinal Membrane Involvement in Unilateral Open-Angle Glaucoma Severity.

Purpose: To determine the relevance of epiretinal membranes (ERMs) in primary open-angle glaucoma (POAG) and potential risk for glaucoma severity. Methods: Sixty eyes of 30 patients with POAG who had a unilateral ERM were analyzed; 60 nonglaucomatous eyes of 30 patients with a unilateral ERM also were recruited in this institutional cross-sectional study. Patients underwent swept-source (SS) optical coherence tomography (OCT) imaging and visual field testing. Intraindividual differences in the SS-OCT retinal nerve fiber layer (RNFL) disc cupping area measurements and visual field outcomes were analyzed in the two groups. Results: In patients with POAG, the mean circumpapillary RNFL thickness in the eyes with an ERM was 75.6 ± 16.5 µm superiorly and 71.8 ± 26.0 inferiorly compared with the fellow eyes without an ERM (87.2 ± 23.6 µm, P = 0.0061 and 81.3 ± 27.7 µm, P = 0.034, respectively). The areas of disc cupping and cup-to-disc ratio seen on OCT horizontal and vertical B-scans were larger in eyes with an ERM than in the fellow eyes without ERM (P = 0.0004 and P = 0.0011, respectively). The average mean deviations were -11.6 ± 7.5 dB in the ERM group and -8.19 ± 6.4 dB in the group with no ERM (P = 0.029). Eyes with an ERM received more antiglaucoma eye drops (P = 0.018). Those differences were not seen between eyes with an ERM or fellow eyes in patients without glaucoma. Conclusions: The presence of an ERM can be a potential risk factor for unilateral severity in eyes with POAG.

Simulation of panretinal laser photocoagulation using geometric methods for calculating the photocoagulation index.

PURPOSE: To establish geometrically based methods for simulating panretinal laser photocoagulation (PRP) for the photocoagulation index. METHODS: A formula for calculating the curved surface area of a spherical dome was used for the simulation. If the radius of the dome is c and the height of the dome is h, then the curved surface area (S) of the dome is S = π (c2 + h2). We calculated the area of the whole retina using this formula and the anatomical dimensions of the standard eyeball. To simulate PRP with a 400-µm spot on the retina with 1-spot spacing, we drew 400-µm-diameter circles, separated by 400 µm, on a retinal map. We calculated the ratio of the total retinal photocoagulated area to the whole retina, termed the photocoagulation index, in order to investigate the impact of the extent of the photocoagulated area and the pulse duration on PRP. RESULTS: The whole retinal area was 1,092 mm2. The numbers of spots in the scattered and full-scattered PRP were 1,222 and 1,814, respectively. The photocoagulation index was 14.1% and 20.9% for scattered and full-scattered PRP, respectively. These values changed to 14.3% (5.6%) and 21.3% (8.3%), respectively, for PRP with a 100-ms pulse or a 20-ms pulse. CONCLUSIONS: This method will be useful for investigating the impact of various PRP parameters (duration, spacing, intensity of burns, extent of photocoagulated area, etc.) on the photocoagulation index.