Efficacy and Safety of Switching Latanoprost Monotherapy to Bimatoprost Monotherapy or Combination of Brinzolamide and Latanoprost.

PURPOSE: To prospectively assess the efficacy and safety of switching to bimatoprost monotherapy or brinzolamide and latanoprost combination therapy in patients who had been receiving latanoprost monotherapy. METHODS: A prospective, open-label study was conducted. Patients with primary open-angle glaucoma or ocular hypertension who had been receiving latanoprost monotherapy for three months or more were enrolled. Bimatoprost was substituted for latanoprost in one eye (BIM group), and brinzolamide was added to the latanoprost in the other eye (BRZ group) simultaneously. The patients underwent examinations at 6 weeks (visit 1) and 12 weeks (visit 2) after changing therapies. Subsequently, the treatments were returned to latanoprost monotherapy. The patients underwent another examination 6 weeks (visit 3) after the return to latanoprost. The parameters examined were intraocular pressure (IOP), conjunctival hyperemia, and corneal epithelial damage. RESULTS: Twenty-six patients (13 men and 13 women) completed the protocol. Both groups showed a significant IOP reduction at visits 1 and 2 compared with the baseline, with a similar magnitude (BIM group: P = 0.016 at visit 1, P = 0.025 at visit 2, BRZ group: P = 0.0006 at visit 1, P = 0.028 at visit 2). The IOPs at the baseline and on visit 3 were similar in both groups (P = 0.7). The two groups showed no changes in either conjunctival hyperemia or corneal epithelial damage compared with the baseline. CONCLUSION: Bimatoprost monotherapy and brinzolamide adjunctive to latanoprost similarly reduced the IOP, with no additive adverse effects, compared with latanoprost monotherapy.

Genetic and clinical factors associated with reticular pseudodrusen in exudative age-related macular degeneration.

BACKGROUNDS: Reticular pseudodrusen (RPD) is considered to be a distinct entity from soft drusen and a risk factor for age-related macular degeneration (AMD). In the present study, we investigate the genetic and clinical factors associated with reticular pseudodrusen (RPD) in patients with exudative AMD, including polypoidal choroidal vasculopathy (PCV), typical neovascular AMD, and retinal angiomatous proliferation (RAP). METHODS: The presence or absence of RPD was studied among 408 patients with exudative AMD in at least one eye, and the clinical characteristics of those with RPD were investigated as well as genetic polymorphisms of ARMS2 A69S (rs10490924) and CFH I62V (rs800292). Subfoveal choroidal thickness was also evaluated in a limited number of subjects using the EDI mode of spectral-domain optical coherence tomography. RESULTS: The prevalence of RPD was significantly higher in RAP eyes than in typical neovascular AMD or in PCV eyes (38.2% of 26 eyes, 13.6% of 132 eyes and 0% of 250 eyes respectively, P < 0.0001). RPD was significantly more prevalent in the elderly (P < 0.0001) and female (P < 0.0001) subjects. The subfoveal choroidal thickness was thinner in eyes with RPD than in those without (129.7 ± 61.7 µm vs 42.6 ± 84.9 µm, P < 0.0001). The frequency of risk variants of ARMS2 A69S was significantly higher in eyes with RPD than in those without RPD (85.7% vs 63.8%, P = 0.0009), although the frequency of CFH I62V was not significantly different between those with and without RPD. Logistic regression analysis revealed that age (odds ratio [OR]:1.10; 95% confidence interval [CI]: 1.04-1.18; p = 0.002), female gender (OR:4.26; 95%CI: 1.72-10.4; p = 0.002), T-allele at ARMS2 A69S (OR: 3.23; 95%CI: 1.36-7.68; p = 0.008) and RAP (OR: 4.25; 95%CI:1.49-12.1; p = 0.007) were risk factors for RPD. CONCLUSIONS: Among eyes with exudative AMD, RPD is more common in eyes with RAP having a thin choroid at the fovea, especially in old, female patients with the risk variant of ARMS2 A69S.

Systemic risk factors associated with polypoidal choroidal vasculopathy and neovascular age-related macular degeneration.

PURPOSE: To compare the association of systemic risk factors between neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV). METHODS: Seven hundred and three patients (235 with nAMD and 468 with PCV) were included. Associated systemic conditions, including hypertension, cardiovascular disease, stroke, diabetes mellitus, and end-stage renal disease, were investigated through an interview and questionnaire. RESULTS: The prevalence of diabetes mellitus and end-stage renal disease in nAMD was significantly higher than that in PCV (P < 0.001 and P = 0.021, respectively, multivariate logistic regression analysis). Moreover, in diabetic patients with nAMD or PCV, the more severe form of diabetic retinopathy was more prevalent in nAMD cases than in PCV cases (P = 0.006, multivariate logistic regression analysis). CONCLUSION: Diabetes mellitus and end-stage renal disease are more prevalent in patients with nAMD than in those with PCV. Specific systemic conditions might be associated with the development of nAMD.

Comparison of a remote operating slit-lamp microscope system with a conventional slit-lamp microscope system for examination of trabeculectomy eyes.

PURPOSE: To compare 2-dimensional (2D) photo imaging with slit-lamp photo imaging for examination of trabeculectomy eyes, and to compare the accuracy and consistency of examination of trabeculectomy eyes with a remote operating slit-lamp microscope system (referred to as "remote slit lamp" hereafter) and a conventional slit-lamp microscope system (referred to as "slit lamp" hereafter). METHODS: Thirty-five eyes of 35 patients having a history of trabeculectomy were enrolled in the study that compared 2D photo imaging with slit-lamp photo imaging for the evaluation of trabeculectomy eyes. Five ophthalmologists evaluated the 2D images and the slit-lamp images independently with masking of patient information. Evaluation scores were compared with those provided by a glaucoma specialist using the slit lamp as standard. Fifteen eyes from 15 patients having a history of trabeculectomy were enrolled in the study that investigated the accuracy and consistency of examination of trabeculectomy eyes with a remote slit lamp and a slit lamp. RESULTS: Central anterior chamber depth, bleb height, and bleb extent evaluated by the slit-lamp photo imaging showed significantly higher consistency with the standard than those evaluated by 2D photo imaging (P<0.05). The remote slit lamp showed good consistency of all the evaluated parameters with the slit lamp and the κ scores of all the evaluated parameters were higher than 0.8. The completion time for evaluation with the remote slit lamp and the slit lamp were 247.3±153.5 and 123.5±53.7 seconds, respectively (P<0.001). CONCLUSIONS: Slit-lamp photo imaging is a superior method for examination of trabeculectomy eyes compared with 2D photo imaging. The remote slit-lamp system shows similar potential to the slit-lamp system for the evaluation of trabeculectomy eyes, although the evaluation time is much longer.

Reappraisal of spontaneous closure rate of idiopathic full-thickness macular holes.

We retrospectively reviewed the records of 142 eyes of 138 patients with idiopathic full-thickness macular hole. Spontaneous closure of idiopathic full-thickness macular hole was observed in five eyes (3.5%) of four patients before the planned vitrectomy. In the era when surgical treatment was not available for macular hole, the rate of spontaneous closure of idiopathic full-thickness macular hole was reported as 6.2%. Among several case reports on spontaneous closure of idiopathic full-thickness macular hole based on the optical coherence tomography images only one study reported the rate of spontaneous closure as 2.7%. According to the previous reports and our results, small idiopathic full-thickness macular holes may close spontaneously in a few percent of all macular hole cases. The rate of spontaneous closure may be affected by the waiting time before vitrectomy.

Foveal sensitivity and visual acuity in macular thickening disorders.

PURPOSE: To study the relationship between foveal sensitivity and visual acuity in eyes with macular disorders exhibiting macular thickening. METHODS: We studied the relationship between foveal sensitivity, obtained as the "foveal threshold" by use of Humphrey perimetry, and best-corrected visual acuity, converted to the logarithm of the minimum angle of resolution (logMAR), for 117 eyes with epiretinal membrane (ERM), 197 eyes with retinal vein occlusion associated with macular edema (RVOME), and 158 eyes with central serous chorioretinopathy (CSC). RESULTS: Foveal sensitivity and logMAR correlated significantly for the eyes with ERM, RVOME, and CSC. Although mean foveal sensitivity was no different among the three diseases, mean logMAR was lower in eyes with CSC, i.e., visual acuity was better, than in those with ERM or RVOME (P < 0.001). CONCLUSIONS: Light sense (foveal sensitivity) is related to spatial resolution (logMAR) at the center of the fovea, in eyes with ERM, RVOME, and CSC at different strengths depending on the disease. Less pronounced reduction of visual acuity compared with foveal sensitivity in eyes with CSC could explain the tendency of these patients to complain of dimness rather than acuity loss.

Recurrence of macular edema associated with branch retinal vein occlusion after intravitreal bevacizumab.

PURPOSE: To study the recurrence of macular edema and the probability of retreatment with intravitreal bevacizumab (IVB) of eyes with macular edema associated with branch retinal vein occlusion (BRVO). METHODS: In this retrospective study of an interventional case series, the temporal profile of visual acuity and retinal thickness after individual IVB, either initial or repeated, was investigated for eyes with acute BRVO associated with symptomatic macular edema. RESULTS: In a total of 95 IVB treatment sessions conducted on 37 eyes of 37 patients, 25 injections were completed with a follow-up period of 6 months or longer without any additional treatments. Fifty-eight IVB injections were followed by retreatment with IVB after an average interval of 119 days (range 42-308 days) since the preceding IVB injection. The remaining 12 injections were followed either by an insufficient follow-up period of less than 6 months or by laser treatment. CONCLUSIONS: Although retreatment with IVB because of recurrence of macular edema is common, in this study, the probability of retreatment with IVB was approximately 70% after each individual IVB injection, indicating that 4 injections is maximum for three-quarters of eyes with BRVO macular edema.

Classic choroidal neovascularization developing after photodynamic therapy in eyes with polypoidal choroidal vasculopathy.

PURPOSE: To investigate the characteristics of eyes with polypoidal choroidal vasculopathy (PCV) which develop secondary classic choroidal neovascularization (CNV) after photodynamic therapy (PDT). METHODS: We retrospectively reviewed the records of 64 eyes of 64 PCV patients (43 men, 21 women; mean age ± standard deviation, 72.7 ± 8.6 years), who were followed-up for at least 1 year after the initial PDT. There was no evidence of classic CNV in any of the subject eyes on fluorescein angiography (FA) at the first PDT. Eyes which developed of secondary classic CNV after PDT were classified as the CNV group and the other eyes as the No-CNV group. RESULTS: Secondary classic CNV developed after PDT in 10 (15.6%) of the 64 eyes. Six patients developed CNV within 1 year after the first PDT. Multivariate logistic regression analysis for the baseline factors related to CNV development, including age, gender, greatest linear dimension, and the lesion components, revealed that in the CNV group the age was significantly younger (p = 0.037) and the incidence of retinal edema was significantly greater (p = 0.041) than in the No-CNV group. CONCLUSIONS: Secondary classic CNV tends to develop after PDT in PCV eyes in younger patients with retinal edema.

Role of complement factor H I62V and age-related maculopathy susceptibility 2 A69S variants in the clinical expression of polypoidal choroidal vasculopathy.

PURPOSE: To investigate the role of complement factor H (CFH) I62V (rs800292) and age-related maculopathy susceptibility 2 (ARMS2) A69S (rs10490924) variants in the clinical characteristics of polypoidal choroidal vasculopathy (PCV). DESIGN: Cross-sectional study. PARTICIPANTS: A total of 226 Japanese patients with PCV in both eyes (44 cases) or in 1 eye (182 cases). METHODS: Genotyping was performed in all cases for CFH I62V using TaqMan technology and for ARMS2 A69S by denaturing high-performance chromatography. The incidence of 5 characteristic funduscopic findings was studied, including serous retinal detachment, subretinal hemorrhage, serous pigment epithelial detachment (PED), hemorrhagic PED, and classic choroidal neovascularization (CNV). MAIN OUTCOME MEASURES: The association of clinical phenotypes, including the incidence of each of 5 specific fundus findings, bilaterality of the disease, and age at onset, with variants of CFH I62V or ARMS2 A69S. RESULTS: Although there was no association of CFH I62V variants with any of the phenotypes in PCV, at-risk variants of ARMS2 A69S were associated with higher incidences of subretinal hemorrhage, serous PED, and hemorrhagic PED. In particular, the at-risk allele homozygosity of ARMS2 A69S increased the likelihood for hemorrhagic PED by 12.4-fold compared with non-carriers of the allele (confidence interval, 1.60-95.1, P = 0.0001). However, the at-risk allele of ARMS2 A69S was associated with a lower incidence of serous retinal detachment (P = 0.0092). Classic CNV was not associated with either variant. The mean age at the onset of PCV was significantly younger (68.8 years) in those with homozygosity of the at-risk allele of ARMS2 A69S than in those with heterozygosity (71.6 years) or in non-carriers (72.6 years) (P = 0.026). Moreover, the at-risk allele frequencies of the ARMS2 A69S were significantly higher in bilateral cases than in unilateral cases (75.0% vs. 59.3%, P = 0.007). CONCLUSIONS: ARMS2 A69S variants were significantly associated with hemorrhagic or subpigment epithelium lesions of PCV, and with earlier onset and bilateral involvement. The genotyping of ARMS2 A69S is more informative than that of CFH I62V in understanding the clinical features in patients with PCV.

Retinal thickness and perimetric sensitivity in central serous chorioretinopathy.

PURPOSE: To investigate the relationship between anatomical changes and visual sensitivity in eyes with central serous chorioretinopathy (CSC). METHODS: Twenty-one eyes with CSC were retrospectively studied using optical coherence tomography (OCT) retinal maps, line scan mode, and the Humphrey perimetry central 10-2 program. RESULTS: Total retinal thickness (TRT), including the neurosensory retina and subretinal fluid, correlated significantly with the sensitivity loss in the corresponding visual field in the central macula within a circle 6 mm in diameter. Differential analysis of the TRT, separating it into neurosensory retinal thickness (NRT) and subretinal thickness (SRT), revealed that only SRT correlated well with perimetric sensitivity at 1°, 3°, 5°, 7°, and 9° from the fovea along horizontal and vertical lines crossing at the fovea. CONCLUSIONS: Visual sensitivity measured with automated static perimetry is further attenuated by increasing distance between the photoreceptor and retinal pigment epithelium (RPE) in areas of serous retinal detachment in eyes with CSC.

Association of LOC387715 A69S genotype with visual prognosis after photodynamic therapy for polypoidal choroidal vasculopathy.

PURPOSE: To investigate whether there is an association of the LOC387715 A69S genotype with visual prognosis after photodynamic therapy in eyes with polypoidal choroidal vasculopathy (PCV). METHODS: Photodynamic therapy was repeated every 3 months until the disappearance of angiographic signs of active lesions in 71 eyes of 71 patients with PCV who were followed-up for at least 12 months. All patients were genotyped for LOC387715 A69S polymorphism (rs10490924, risk-allele T). RESULTS: Although there was no statistically significant difference in the mean baseline visual acuity (P = 0.53) among the 3 genotypes, there was a statistically significant difference in the visual acuity both at the 12-month and final visits (P = 0.002 and P < 0.001, respectively) with the poorer acuity in patients with the higher "T-"allele frequency. "T" allele was more frequently observed in those with the recurred PCV lesions (odds ratio: 5.8, 95% confidential interval: 2.3-15.1, T vs. G). CONCLUSION: There is a pharmacogenetic association between the LOC387715 A69S variant and the long-term results after photodynamic therapy in eyes with PCV. The LOC387715 A69S genotype is of clinical importance to predict the visual prognosis after photodynamic therapy in eyes with PCV. These results should be confirmed or refuted by replication studies.

Photodynamic therapy for polypoidal choroidal vasculopathy: baseline perimetric results and visual outcomes.

PURPOSE: To investigate whether the baseline mean deviation (MD) of Humphrey perimetry has a predictive value for visual improvement after photodynamic therapy (PDT) for polypoidal choroidal vasculopathy (PCV). METHODS: We retrospectively reviewed the records of 40 eyes of 39 PCV patients (28 men, 11 women) who underwent PDT. The follow-up period ranged from 12 to 42 months. Best-corrected visual acuity (BCVA) improved more than 0.2 logarithm of the minimum angle of resolution (logMAR) units at the final examination in 22 (55%) of the 40 eyes, which were classified into the "Improved group." The other 18 eyes with improvement of

Angiographic lesion size associated with LOC387715 A69S genotype in subfoveal polypoidal choroidal vasculopathy.

PURPOSE: To investigate whether the LOC387715/ARMS2 variants are associated with an angiographic phenotype, including lesion size and composition, in subfoveal polypoidal choroidal vasculopathy. METHODS: Ninety-two subjects with symptomatic subfoveal polypoidal choroidal vasculopathy, whose visual acuity was from 0.1 to 0.5 on the Landolt chart, were genotyped for the LOC387715 polymorphism (rs10490924) using denaturing high-performance chromatography. The angiographic phenotype, including lesion composition and size, was evaluated by evaluators who were masked for the genotype. Lesion size was assessed by the greatest linear dimension based on fluorescein or indocyanine green angiography. RESULTS: Although there was no statistically significant difference in lesion size on indocyanine green angiography (P = 0.36, Kruskal-Wallis test) and in lesion composition (P = 0.59, chi-square test) among the 3 genotypes, there was a statistically significant difference in lesion size on fluorescein angiography (P = 0.0022, Kruskal-Wallis test). CONCLUSION: The LOC387715 A69S genotype is not associated with lesion composition or size on indocyanine green angiography but with lesion size on fluorescein angiography in patients with subfoveal polypoidal choroidal vasculopathy. Because fluorescein angiography findings represent secondary exudative changes, including subretinal hemorrhages and retinal pigment epithelial detachment, the results in the present study likely indicate that the T allele at the LOC387715 gene is associated with the exudative activity of polypoidal lesions.

Release of vitreomacular traction following retinal photocoagulation in an eye with branch retinal vein occlusion.

Infrequently, vitreomacular traction is released through the spontaneous development of complete posterior vitreous detachment (PVD). PVD caused by laser photocoagulation has also been reported. A 62-year-old woman with ischemic branch retinal vein occlusion showed decreased vision in the affected eye due to vitreomacular traction. We performed laser photocoagulation in the ischemic retinal area in the hope of eliminating vitreomacular traction through laser-induced PVD. Forty days later, her vision improved and the release of vitreomacular traction was observed, associated with PVD. Optical coherence tomography demonstrates clearly the change of vitreomacular interface before and after photocoagulation.

Association of LOC387715 A69S with vitreous hemorrhage in polypoidal choroidal vasculopathy.

PURPOSE: To investigate whether the LOC387715 polymorphism is associated with polypoidal choroidal vasculopathy (PCV) and with vitreous hemorrhage (VH), one of the most severe clinical phenotypes, in the Japanese population. DESIGN: Cross-sectional case-control association study. METHODS: One hundred and nine Japanese patients with PCV, composed of nine patients associated with VH (VH group) and 100 patients without VH (non-VH group), and 85 control subjects were analyzed for the LOC387715 polymorphism (rs = 10490924), using denaturing high-performance chromatography. RESULTS: There was a significant difference in the T allele frequency between PCV patients and control subjects (P < .0001). In comparison with wild-type homozygosity (GG), homozygosity for the at-risk allele genotype (TT) increased the likelihood for PCV 8.4-fold (3.6 to 19.5, 95% confidence interval [CI]) and heterozygosity for the at-risk allele genotype (TG) increased the likelihood for PCV 4.0-fold (1.9 to 8.4, 95% CI). There was a significant difference in the genotypic frequency at the LOC387715 site between the VH and non-VH groups (P = .0099, Chi-square test) with the TT genotype occurring in 88.9% in the VH group and 37.0% in the non-VH group. The frequency of the T allele in the VH group was significantly greater than that in the non-VH group (0.944 vs 0.610; P = .0039, Fisher exact test). CONCLUSIONS: The LOC387715 polymorphism is associated with PCV and clinical severity in the subgroups of PCV in the Japanese population.

Different expression role among glutamate transporters in rat retinal glial cells under various culture conditions.

Using cultured rat retinal glial cells, the changes in the expression of glutamate transporters (GLTs) under such conditions as the degree of confluence of the cells, hypoxia, glutamate loading, and potassium loading, were assessed. After the retinal glial cells were isolated from 3-day-old Sprague-Dawley rats, GLAST, GLT-1, and EAAC1 mRNA expression was confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and their protein expression was confirmed by Western blot analysis and immunostaining. Changes in the expression of the GLTs at 6 h after passage and at confluence, during culture in 5% oxygen, during glutamate loading and during potassium loading were assessed using real-time PCR. Although the GLAST mRNA expression was increased during glutamate and potassium loading, no changes in the expression were observed during hypoxia and at confluence. By contrast, the GLT-1 mRNA expression was increased during hypoxia and at confluence, but not during glutamate and potassium loading, and the EAAC1 mRNA expression was not changed only during glutamate loading. The expression of EAAC1 in the cultured retinal glial cells was confirmed. The expression of the GLTs varied according to the environment and the type of load suggests that the involvement of the GLTs in retinal physiology and pathology varies depending on the subtype.