MACULAR ATROPHY FINDINGS BY OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY COMPARED WITH FUNDUS AUTOFLUORESCENCE IN TREATED EXUDATIVE AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To compare the areas of choriocapillaris (CC) nonperfusion and macular atrophy (MA) in treated exudative age-related macular degeneration. METHODS: This was a prospective, observational, cross-sectional study. Forty-four eyes exhibiting MA (42 patients with age-related macular degeneration), with a dry macula, underwent fundus autofluorescence and optical coherence tomography angiography. The area of MA detected by fundus autofluorescence and CC nonperfusion detected by optical coherence tomography angiography was measured using image analysis software. The rates of concordance between the MA and CC nonperfusion areas were calculated. We qualitatively and quantitatively compared the areas of MA and CC nonperfusion in age-related macular degeneration eyes. RESULTS: The mean areas of MA and CC nonperfusion were 5.95 ± 4.50 mm and 10.66 ± 7.05 mm, respectively (paired t-test, P < 0.001). In 39 eyes (88.6%), the CC nonperfusion area was larger than the MA area, and the mean CC nonperfusion area was significantly larger than the mean MA area. Fundus autofluorescence matching optical coherence tomography angiography showed that the CC nonperfusion area was almost included in the MA area. The mean concordance rate for the MA area inside the CC nonperfusion area was 87.7 ± 13.9%. CONCLUSION: The MA and CC nonperfusion areas markedly overlapped. The area of CC nonperfusion correlated with the MA area. Choroidal ischemia might be involved in the pathogenesis of MA in treated age-related macular degeneration.

One-year outcomes of fixed treatment of intravitreal aflibercept for exudative age-related macular degeneration and the factor of visual prognosis.

The aim of this study was to investigate the efficacy of periodic intravitreal aflibercept (IVA) in exudative age-related macular degeneration, and to explore the predictive factors for visual outcome.This is a prospective interventional case series.Fifty-two eyes of 52 treatment-naïve age-related-macula-degeneration patients were enrolled. All participants received IVA bimonthly following 3 monthly loading dose. The primary endpoint was change in best corrected visual acuity (BCVA) and central retinal thickness (CRT), and the secondary outcomes included changes in subfoveal choroidal thickness (SCT), macular atrophy (MA), and retinal average sensitivity (AS) determined by microperimetry at 12 months compared with baseline. The predictive factors for the change of BCVA were examined.Of 52 enrolled patients, 4 patients were drop out. Remaining 48 patients were examined. Mean logMAR BCVA significantly improved from 0.42 ±â€Š0.37 at baseline to 0.29 ±â€Š0.34 at 12 months (P = .008). Mean CRT and SCT significant reduced from 285.6 ±â€Š135.2 µm, 247.9 ±â€Š96.7 µm at baseline to 233.4 ±â€Š98.0 µm, 208.1 ±â€Š94.6 µm at 12 months, respectively (P < .001). At 12 months, 35 eyes of 48 eyes (72.3%) were archived dry macula. MA occurred in 7 eyes of 35 eyes with dry macula at 12 months (20.0%). AS was significant improved (P = .027) between baseline (median: 15.7 dB) and 12 months (median: 19.5 dB). The BCVA of the cases with MA involved fovea was significant worse. Age was significantly predicted for the BCVA at 12 months.IVA administered over 1 year improved BCVA, AS, and morphological findings, and the predictive factors for BCVA were age and MA-involved fovea.

Elevated plasma aldosterone levels are associated with a reduction in retinal ganglion cell survival.

OBJECTIVE: The purpose of this article is to investigate the relationship between the plasma concentration of aldosterone and changes in the number of retinal ganglion cells (RGCs) after systemic administration of aldosterone. METHODS: An osmotic minipump that was subcutaneously implanted into the midscapular region of rats administered 40, 80 or 160 µg/kg/day aldosterone or vehicle. Enzyme immunoassay kits were used to measure the plasma aldosterone concentrations two weeks after the systemic administration of aldosterone or vehicle. Six weeks after these systemic administrations, the number of RGCs was measured. RESULTS: The plasma aldosterone concentrations at two weeks after systemic administration of vehicle or 160 µg/kg/day aldosterone were 238 ± 17 pg/ml and 1750 ± 151 pg/ml (748.5% ± 183.2%), respectively. There was a significant decrease in the number of RGCs in the central retina of the rats after the administration of either 80 or 160 µg/kg/day aldosterone. In the peripheral retina, however, there was a significant decrease in the number of RGCs in 40, 80 or 160 µg/kg/day aldosterone. There was a significant correlation between the number of RGCs and plasma aldosterone concentration. CONCLUSIONS: After systemic administration of aldosterone, there was a negative correlation between the plasma aldosterone concentration and the number of RGCs.

Clinical Features of Central Serous Chorioretinopathy With Type 1 Choroidal Neovascularization.

PURPOSE: To evaluate the type 1 choroidal neovascularization (CNV) incidence and associated factors in eyes with central serous chorioretinopathy (CSC). DESIGN: Retrospective case series. METHODS: Records of 363 eyes (324 patients) with CSC were reviewed. Age, sex, CSC type, choroidal vascular hyperpermeability (CVH), best-corrected visual acuity (BCVA), subfoveal choroidal thickness (SCT), and systemic hypertension (HT) were assessed and compared between subjects with and without neovascular CSC. RESULTS: We identified 219 and 144 eyes with chronic and acute CSC, respectively. The mean participant age was 55.2 ± 12.0 years, and 58 (15.6%) eyes had neovascular CSC. Age (no CNV: 54.8 ± 12.1 years, CNV: 57.3 ± 10.9 years; P = .118) and SCT (no CNV: 388.0 ± 104.5 µm, CNV: 377.4 ± 108.9 µm; P = .487) were comparable between eyes with and without CNV. However, BCVA (logarithm of the minimum angle of resolution) was significantly worse in subjects with CNV (0.28 ± 0.33 [20/38] vs 0.15 ± 0.29 [20/28]; P = .014). Neovascular CSC occurred more often in women (72 [23.6%] vs 20 [34.5%], P = .099) and in cases of chronic CSC (171 [56.1%] vs 48 [82.8%], P < .001), CVH (205 [67.2%] vs 58 [100%], P < .001), and HT (91 [29.8%] vs 24 [41.4%], P = .092). Chronic CSC (P = .001), female sex (P = .075), and poor BCVA (P = .091) were associated with neovascular CSC (multiple regression). CONCLUSIONS: Chronic CSC, female sex, CVH, and poor BCVA are risk factors for CNV in eyes with CSC.

Gene expression changes in the retina after systemic administration of aldosterone.

PURPOSE: Retinal ganglion cell (RGC) loss associated with thinning of the retinal nerve fiber layer without elevated intraocular pressure (IOP) occurs after the systemic administration of aldosterone. Since it is important to determine the mechanism of cell death independent of the IOP, we examined gene expression changes in the retina after the systemic administration of aldosterone. METHODS: Following subcutaneous implantation of an osmotic minipump into the mid-scapular region of rats, we administered an 80 µg/kg/day dose of aldosterone. Differences in the gene expression in the retina between normal rats and aldosterone-treated rats were investigated using microarrays. Real-time PCR was used to confirm the differential expression. RESULTS: Analysis of the microarray data sets revealed the upregulation of 24 genes and the downregulation of 24 genes of key apoptosis-specific genes. Real-time PCR revealed 4 genes (Cdkn1a, Tbox5, Pf4, Vdr) were upregulated while 12 genes (Acvr1c, Asns, Bard1, Card9, Crh, Fcgr1a, Inhba, Kcnh8, Lck, Phlda1, Ptprc, Sh3rf1) were downregulated. CONCLUSIONS: Significant increases and decreases were noted in several genes after the systemic administration of aldosterone. Further studies will need to be undertaken in order to definitively clarify the role of these genes in the eyes of animals with normal-tension glaucoma.

CLINICAL FEATURES OF TREATED AND UNTREATED TYPE 1 IDIOPATHIC MACULAR TELANGIECTASIA WITHOUT THE OCCURRENCE OF SECONDARY CHOROIDAL NEOVASCULARIZATION FOLLOWED FOR 2 YEARS IN JAPANESE PATIENTS.

PURPOSE: To evaluate the clinical features of Type 1 idiopathic macular telangiectasia (IMT) followed up for 2 years. METHODS: Forty-nine patients with unilateral Type 1 IMT were examined. Thirty-one IMT eyes were treated with direct laser photocoagulation and/or intravitreal bevacizumab; the remaining 18 eyes, with good vision or slight macular edema, were untreated. Changes in best-corrected visual acuity and central retinal thickness between baseline and 24 months after the initial visit were examined. RESULTS: Of 49 eyes, nine were treated with direct laser photocoagulation, 12 with laser photocoagulation and intravitreal bevacizumab, 10 with intravitreal bevacizumab monotherapy, whereas 18 did not receive any treatment. The mean logarithm of the minimum angle of resolution best-corrected visual acuity was 0.20 ± 0.19 (median, 20/29) and 0.13 ± 0.22 (median, 20/25) at baseline and 24 months, respectively (P = 0.023). The mean central retinal thickness was 375.0 ± 94.5 µm and 315.3 ± 78.5 µm at baseline and 24 months, respectively (P < 0.001). Retinal vein occlusion and retinal macroaneurysm occurred in six eyes and one eye, respectively, during follow-up. CONCLUSION: Treatment with laser photocoagulation and/or intravitreal bevacizumab may be effective for Type 1 IMT, 36.7% of IMT eyes required no treatment over a 2-year follow-up, and other retinal vascular events were not uncommon.

The effect of vitreomacular and cataract surgery on oxygen saturation in retinal vessels.

PURPOSE: To evaluate the effects of vitreomacular and cataract surgery on retinal oximetry in vitreomacular disease. PATIENTS AND METHODS: Thirty-eight eyes with epiretinal membrane (ERM) and 15 with idiopathic macular hole (MH) underwent 25 gauge pars plana vitrectomy combined with cataract surgery and intraocular lens implantation. Retinal oximetry was performed using the Oxymap T1 before, 1 month, and 6 months after surgery. Oxymap T1 simultaneously captures monochrome images of the fundus at two different wavelengths of light. Built-in Oxymap Analyzer software measures the oxygen saturation and vessel diameter. RESULTS: Mean arterial oxygen saturation significantly increased from 96.8%±6.2% to 100.2%±5.8% at 1 month and to 99.6%±5.8% at 6 months after surgery (P<0.01). Mean venous oxygen saturation also significantly increased from 54.6%±7.5% to 61.2%±6.4% at 1 month and to 62.6%±5.9% at 6 months after surgery (P<0.01). Mean arteriovenous (A-V) difference decreased from 42.2%±6.6% to 39.0%±7.8% at 1 month and to 37.0%±6.9% at 6 months after surgery (P<0.01). The ERM and MH groups showed similar changes in retinal oxygen saturation. However, there were no significant changes in the caliber of major retinal vessels after surgery (from 125.2±15.2 µm to 124.0±15.4 µm in artery, from 168.7±14.6 µm to 169.8±14.6 µm in vein). CONCLUSION: Oxymap T1 was able to measure the increase in oxygen saturation in retinal arteries and veins, which led to a decrease in the A-V difference in oxygen saturation after vitrectomy combined with cataract surgery.

The Relationship Between the Renin-Angiotensin-Aldosterone System and NMDA Receptor-Mediated Signal and the Prevention of Retinal Ganglion Cell Death.

Purpose: Excitotoxicity, which is due to glutamate-induced toxic effects on the retinal ganglion cell (RGC), is one of several mechanisms of RGC loss. The renin-angiotensin-aldosterone system (RAAS) has also been implicated in RGC death. Therefore, it is important to determine the exact relationship between the RAAS and N-methyl-d-aspartate (NMDA) receptor-mediated signal in order to prevent RGC death. Methods: N-methyl-d-aspartate or aldosterone was injected into the vitreous body. After intravitreal injection of NMDA or aldosterone, animals were treated with spironolactone or memantine. Retinal damage was evaluated by measuring the number of RGCs at 4 weeks after local administration of aldosterone or at 2 weeks after local administration of NMDA. Vitreous humor levels of aldosterone were measured using enzyme immunoassay kits. Results: A significantly decreased number of RGCs were observed after intravitreal injection of NMDA. Although spironolactone did not show any neuroprotective effects, memantine significantly reduced NMDA-induced degeneration in the retina. Furthermore, a significant decrease in the number of RGCs was observed after an intravitreal injection of aldosterone. While memantine did not exhibit any neuroprotective effects, spironolactone caused a significant reduction in the aldosterone-induced degeneration in the retina. There was no change in the aldosterone concentration in the vitreous humor after an NMDA injection. Conclusion: Our findings indirectly show that there is no relationship between the RAAS and NMDA receptor-mediated signal with regard to RGC death.

Retinal Oximetry in a Healthy Japanese Population.

PURPOSE: To establish the normative database of retinal oximetry using Oxymap T1 in a healthy Japanese population, and study the reproducibility of the measurements in Japanese. METHODS: We measured oxygen saturation in the major retinal vessels with Oxymap T1 in 252 eyes of 252 healthy Japanese subjects. Fundus images acquired using Oxymap T1 were processed using built-in Oxymap Analyzer software. Reproducibility of retinal oximetry was investigated using 20 eyes of 20 healthy subjects. RESULTS: The mean retinal oxygen saturation of 4 quadrants in healthy Japanese was 97.0 ± 6.9% in arteries and 52.8 ± 8.3% in veins. The mean arteriovenous difference in oxygen saturation was 44.2 ± 9.2%. Both arterial and venous oxygen saturation were significantly lower in the temporal side of the retina, especially in the temporal-inferior vessels. However, the arteriovenous difference in oxygen saturation was limited in the 4 quadrants. Interphotograph, intervisit, and interevaluator intraclass correlation coefficients were 0.936-0.979, 0.809-0.837, and 0.732-0.947, respectively. In the major retinal arteries, oxygen saturation increased with age (r = 0.18, p<0.01), at a rate of 0.67% per 10 years. However, venous oxygen saturation showed no correlation with age. CONCLUSIONS: This study provides the normative database for the Japanese population. The arterial saturation value appears to be higher than other previous studies. Mean retinal oximetry in 4 quadrants with Oxymap T1 has high reproducibility.

Six-month results of intravitreal aflibercept injections for patients with polypoidal choroidal vasculopathy.

BACKGROUND: This study aims to evaluate the therapeutic effect of intravitreal aflibercept injection for polypoidal choroidal vasculopathy (PCV). METHODS: Eighteen eyes of 17 consecutive patients with PCV received three consecutive monthly intravitreal injections of aflibercept and one additional injection 2 months later (four injections totally). All patients underwent eye examinations, which included best-corrected visual acuity (BCVA), fluorescein angiography, indocyanine green angiography, and optical coherence tomography. The primary endpoint of the study was the regression of polypoidal lesions. The secondary endpoints were BCVA, central retinal thickness (CRT) and changes in retinal exudation. RESULTS: Six months after the first aflibercept injection, the polypoidal lesions were completely resolved in 14 eyes (77.7%) and partially resolved in 4 eyes (22.2%). Although branching choroidal vascular networks were still present in all eyes, retinal exudative changes had completely resolved in 17 eyes (94.4%), and the mean CRT decreased significantly from 407.2±100.1 µm to 229.1±57.2 µm (p<0.0001). BCVA (logarithm of the minimal angle of resolution, logMAR) improved significantly from 0.414±0.384 at baseline to 0.297±0.334 after 6 months (p=0.016). CONCLUSIONS: At 6 months, aflibercept monotherapy effectively reduced polyps, retinal exudation and CRT in patients with PCV.

Effect of switching therapy to pegaptanib in eyes with the persistent cases of exudative age-related macular degeneration.

Purpose of this study was to evaluate the efficacy of switching to pegaptanib monotherapy for persistent cases of exudative age-related macular degeneration (AMD).Out of 296 eyes of 296 patients treated with ranibizumab or ranibizumab combined with photodynamic therapy (PDT), 50 eyes of 50 AMD patients were found to be resistant to these treatments. Over a 12-month period, intravitreal pegaptanib (IVP) 0.3 mg was administered at intervals of 6 weeks until the exudation disappeared prospectively. All patients were examined with the following tests: best-corrected visual acuity (BCVA) and central retinal thickness (CRT), determined at the initial visit, before the first IVP (baseline), and at 12 months. The factors responsible for achieving dry macula with IVP were examined statistically.The rate of persistent cases with intravitreal ranibizumab (IVR) and/or PDT was 17.0%. The mean number of IVPs administered was 5.4 (range, 2-9). Logarithm of the minimal angle of resolution BCVA at 12 months was stable or improved by ≥ 0.3 in 49 eyes (98.0%), with a significant improvement noted between the baseline and final BCVA (P=0.01, paired t test). The CRT (mean ± standard deviation) was 446.9 ± 150.6 µm at the initial visit, 414.5 ± 146.5 µm at baseline, and 318.7 ± 99.0 µm at 12 months. There was a significant decrease in the mean CRT between the measurements at baseline and at 12 months after the first IVP (P=0.002, Bonferroni correction). At 12 months, the exudative change was completely resolved in 27 eyes (54.0%) and reduced in 21 eyes (42.0%). The number of previous IVR treatments was significantly correlated with dry macula at 12 months.After switching therapy to pegaptanib in persistent cases of AMD, most patients maintained or improved their BCVA and exhibited a positive treatment response at 12 months.

[Medium-term effects of intravitreal bevacizumab for macular edema associated with central retinal vein occlusion].

PURPOSE: To report the medium term effects of intravitreal injection of bevacizumab for central retinal vein occlusion (CRVO) with macular edema. PATIENTS AND METHODS: Twenty-two eyes of 22 patients receiving intravitreal injections of 1.25 mg/0.05 ml of bevacizumab (IVB) were included. All patients were followed up for 6 months or longer after the final IVB. The visual acuity and central retinal thickness (CRT) were measured at baseline, one week and every three months after the first IVB. RESULTS: The mean follow-up after the final IVB was 12.5 months (6-30 months). The mean visual acuity (baseline : 0.63 +/- 0.39) temporarily improved at one week (0.38 +/- 0.33 : p=0.0002), but there was no significant visual improvement at the final visit (0.73 +/- 0.67 : p=1.0). The mean CRT significantly decreased at one week, three months and six months after IVB and at the last visit. There were no differences in either visual or anatomical outcomes between the ischemic type and non-ischemic type. CONCLUSION: Intravitreal injections of bevacizumab should be initially considered as a possible treatment in eyes with macular edema associated with central retinal vein occlusion.

One-year results of reduced-fluence photodynamic therapy for polypoidal choroidal vasculopathy.

PURPOSE: To report 1-year results of reduced-fluence photodynamic therapy (PDT) for polypoidal choroidal vasculopathy (PCV) in Japanese patients. DESIGN: Prospective interventional case series. METHODS: In the present study, 28 treatment-naïve eyes of 28 consecutive patients underwent PDT with a reduced laser fluence of 25 J/cm(2). Patients were followed up at baseline and 1 week and 3, 6, 9, and 12 months after PDT. Choroidal perfusion changes were evaluated by indocyanine green angiography (ICGA) and leakage from PCV lesions and exudative changes by fluorescein angiography and optical coherence tomography. Treatment safety was assessed according to visual acuity (VA) and adverse events. The best-corrected VA (BCVA) obtained by Landolt ring tests was converted into the logarithm of the minimal angle of resolution (logMAR). RESULTS: At baseline, the mean logMAR BCVA was 0.45 (geometric mean: 7/20). At 12 months, the mean logMAR BCVA significantly improved to 0.29 (geometric mean: 10/20) (P = 0.0001). The logMAR BCVA was stable or improved by >or=0.2 in 26 eyes (93%) at 1-year follow-up. In 10 eyes with VA better than 20/40 at baseline, the mean logMAR BCVA was significantly improved compared with baseline at 12 months. Although 16 of 28 eyes (57%) showed mild to moderate nonperfusion of choriocapillaris in early ICGA at 1 week, 27 eyes (96%) showed recovery to pretreatment levels at 3 months. Mean number of treatment sessions during the 12 months was 1.3. No severe side effects related to treatment were encountered. CONCLUSIONS: Reduced-fluence PDT is an effective treatment for PCV and could improve vision even in eyes with VA better than 20/40.