The second eye of Japanese patients with unilateral exudative age related macular degeneration

AIM: To clarify the incidence of choroidal neovascularisation (CNV) and predisposing findings for development of CNV in the second eye of Japanese patients with unilateral exudative age related macular degeneration (AMD). METHODS: The second eyes of unilaterally affected patients with exudative (neovascular) AMD treated in our clinic during the past 10 years (1988-97) were carefully followed up for more than a year. Evidence of CNV was confirmed by fluorescein and indocyanine green angiography. Macular lesions in patients, in whom CNV developed in the second eye, were retrospectively evaluated from patient records. RESULTS: 170 patients met the criteria. The average follow up period was 47 months (range 12-108 months). All patients were Japanese. CNV developed in the second eye in 12 (7%) of 170 patients, 30.3 months on average after the first examination. Cumulative incidence of developing CNV in the second eye using Kaplan-Meier life table analysis was: 0.6% by 1 year, 5.6% by 3 years, and 12.3% by 5 years, and was relatively low compared with that in white patients. CNV developed most frequently from serous pigment epithelial detachment (PED) in the macula (58%). Soft drusen were not prevalent and risk of developing CNV was not very high (18%). CONCLUSION: It was confirmed that there were some differences in the incidence and predisposing findings for CNV developing in AMD among Japanese and other Asian patients compared with those in white people. It is important to recognise these differences between the two populations to understand the pathogenesis and epidemiology of AMD.     

Intravitreal triamcinolone acetonide for exudative age related macular degeneration

AIM: To evaluate the effect of intravitreal triamcinolone acetonide on the visual acuity of patients with exudative age related macular degeneration, to assess the duration of a possible effect, and to evaluate clinical side effects of the treatment. METHODS: The study included 67 patients (71 eyes) who presented with exudative age related macular degeneration of predominantly or total occult type (n = 68) or classic type (n = 3), and who received once, or repeatedly, an intravitreal injection of 25 mg of crystalline triamcinolone acetonide. Mean follow up time was 7.46 (SD 3.54) months (range 3.1-19.57 months). RESULTS: Visual acuity increased significantly (p <0.001) from 0.16 (0.11) to a mean maximum of 0.23 (0.17). Postoperative visual acuity was highest 1-3 months after the injection. 47 (66.2%) eyes gained in maximal visual acuity and 11 (15.5%) eyes lost in visual acuity. Intraocular pressure increased significantly (p <0.001) from 15.1 (3.1) mm Hg at baseline to a maximal value of 23.0 (8.25) mm Hg. At the end of follow up, intraocular pressure again decreased significantly (p<0.001) to 16.8 (4.9) mm Hg. No cases of postoperative infectious endophthalmitis, rhegmatogenous retinal detachment, or proliferative vitreoretinopathy occurred. Owing to a decrease in visual acuity after an initial increase, six patients received a second intravitreal triamcinolone acetonide injection after which visual acuity increased again in three eyes. CONCLUSIONS: Intravitreal injection of 25 mg of crystalline triamcinolone acetonide merits further study for the treatment of exudative age related macular degeneration.     

CST3 genotype associated with exudative age related macular degeneration

AIMS: To determine whether allelic variants of the cystatin C gene CST3 are genetically associated with exudative age related macular degeneration (ARMD). Cystatin C is a cysteine protease inhibitor that regulates the activity of cathepsin S, a protease with central regulatory functions in retinal pigment epithelial cells. METHODS: CST3 of 167 patients with exudative ARMD was genotyped by using polymerase chain reaction of genomic DNA and restriction enzyme digestion with KspI and compared with those of 517 control subjects. Patients and controls were white. RESULTS: There was a significant difference in genotype counts between patients and controls (chi(2) = 7.158, df = 2; Fisher's exact test: p = 0.037). There was no significant difference in allele frequencies between patients and controls and between controls from Germany, Switzerland, Italy, and United States. The significant difference in genotype counts between patients and controls could be explained completely by an excess of the homozygous CST3 genotype B/B in patients with exudative ARMD (6.6%) over controls (2.3%), suggesting an odds ratio for ARMD in association with CST3 B/B of 2.97 (95% CI: 1.28-6.86). The results also suggest a stronger association of B/B with ARMD in males than in females. However, in both males and females there was a similar and significant effect of CST3 B/B on disease free survival assessed by Kaplan-Meier analysis. The mean disease free survival time in pooled males and females with genotypes A/A or A/B was 85 years (SE 1; 95% CI: 83-86) and 76 years (SE 2; 95% CI: 72-79) respectively in B/B homozygotes (log rank p = 0.0006). CONCLUSION: Genotyping data, the absence of a significant difference in allele frequencies between patients and controls, and survival analyses suggest an increased susceptibility for ARMD in CST3 B/B homozygotes. Therefore, CST3 B may be a recessive risk allele, significantly contributing to disease risk in up to 6.6% of German ARMD patients. Functional correlates of the allelic CST3 variants A and B remain to be investigated.     

Pulsatile ocular blood flow in asymmetric exudative age related macular degeneration

BACKGROUND/AIMS: Decreased perfusion or increased vascular resistance of the choroidal vessels had been proposed as the vascular pathogenesis for age related macular degeneration (AMD). This study planned to answer the question whether pulsatile ocular blood flow (POBF) was different in patients with asymmetric exudative AMD between eyes with drusen, choroidal neovascularisation (CNV), or disciform scar. METHODS: 37 patients with asymmetric exudative AMD were enrolled in this observational case series study. POBF were measured in both eyes of each subject. Eyes with high myopia, anisometropia, recent laser treatment, and glaucoma were excluded. RESULTS: After adjusting for ocular perfusion pressure, intraocular pressure, and pulse rate, multivariate regression analysis with generalised estimating equation showed POBF was significantly higher in eyes with CNV (1217 (SD 476) microl/min) than the contralateral eyes with drusen (1028 (385) microl/min) (p = 0.024). Eyes with disciform scar had lower POBF than the contralateral eyes with drusen (999 (262) microl/min and 1278 (341) microl/min, respectively, p<0.001). There was no significant correlation between the POBF and the lesion size of the CNV. CONCLUSION: The POBF in eyes with drusen was lower than their fellow eyes with CNV, but higher than their fellow eyes with disciform scar. This finding suggests that haemodynamic differences between fellow eyes in individuals are relevant to the development of CNV and the formation of disciform scar. Further studies on the follow up patients might shed light on the pathogenesis of exudative AMD.     

Clinical characteristics of exudative age-related macular degeneration in Japanese patients

PURPOSE: To clarify the clinical characteristics of exudative age-related macular degeneration (AMD) in Japanese patients. DESIGN: Retrospective, observational, consecutive case series. METHODS: Two hundred and eighty-nine patients with neovascular AMD were examined. RESULTS: The authors classified the patients into three subtypes of neovascular AMD: polypoidal choroidal vasculopathy (PCV), retinal angiomatous proliferation (RAP), and typical AMD. One hundred and fifty-eight patients (54.7%) were diagnosed with PCV and 102 patients (35.3%) with typical AMD. RAP was observed in 13 patients (4.5%). In 16 patients (5.5%), one eye had PCV and the other eye had typical AMD. Most patients with PCV and typical AMD had unilateral disease (81.6% and 94.1%, respectively) with a male preponderance (77.8% and 71.6%, respectively). Nine of 13 patients with RAP were female (69.2%). Patients with RAP were older (mean, 80.3 years for men and 75.3 years for women) than patients with other subtypes. Serous and hemorrhagic pigment epithelial detachment developed in 69 patients (43.7%) with PCV, 22 patients (21.6%) with typical AMD, and nine patients (69.2%) with RAP. In the patients with unilateral disease in each subtype, large drusen in the unaffected eye were seen in 24.0% with PCV, 30.2% with typical AMD, and 77.8% with RAP. CONCLUSIONS: Neovascular AMD in Japanese patients has different demographic features compared with that in White patients. In Japanese patients, there is a preponderance of PCV, male gender, unilaterality, and absence of drusen in the second eye, with the exception of RAP.     

Utility values in Japanese patients with exudative age-related macular degeneration

Purpose  

To investigate the utility values associated with visual loss due to age-related macular degeneration (AMD) in Japanese patients.     

Pulsatile ocular blood flow study: decreases in exudative age related macular degeneration

BACKGROUND: Pulsatile ocular blood flow (POBF) is a parameter for evaluating choroidal blood flow. POBF in the patients with non-exudative and exudative age related macular degeneration (AMD) was investigated. METHODS: POBF, pulse amplitude (PA), systolic and diastolic blood pressures, intraocular pressure (IOP), refractive error, and axial length were compared among 10 patients with non-exudative AMD, 11 patients with exudative AMD, and 69 age matched controls. A Langham OBF computerised tonometer was used with the participants in the sitting position to measure POBF and PA. RESULTS: No significant differences were found in age, systolic and diastolic blood pressures, IOP, or refractive error between patients with exudative and non-exudative AMD and the control subjects. In the patients with exudative AMD the POBF (median, 372.7 microl/min) and PA (median, 1.2 mm Hg) were significantly lower than in the patients with non-exudative AMD (median, 607.0 microl/min (p = 0.02) and 2.2 mm Hg (p = 0.04), respectively) and control subjects (median, 547.4 microl/min (p = 0.01) and 2.0 mm Hg (p = 0.01), respectively). CONCLUSIONS: These data show that the POBF and PA in the patients with exudative AMD are lower than in the patients with non-exudative AMD and normal subjects. Decreased choroidal blood flow may have a role in the development of choroidal neovascularisation in AMD.     

渗出型老年黄斑变性40例随访观察

为探讨渗出型老年黄斑变性（ＡＭＤ）的病灶损害和视功能改变的发展特征，用视力、眼底彩照和荧光血管造影（ＦＦＡ）、明视视网膜电图（ＥＲＧ）、ＦＭ１００—ｈｕｅ色彩试验分别对４８只、２４只、３５只及１４只渗出型ＡＭＤ患眼进行了随访检测。结果：渗出型ＡＭＤ的病灶损害发展快慢不一，但６５岁以上组，其病灶发展速率比６５岁以下组的要快些（Ｐ＜０．０５）。在平均３３．２个月的随访过程中，有７５．０％的患眼随访终了时的视力在０．１或以下。明视ＥＲＧ和ＦＭ１００—ｈｕｅ色彩试验在随访前后无明显变化。结论：６５岁以上的渗出型ＡＭＤ患者，其病灶损害一般发展较快，大部分患眼在随访终了时视力在０．１或以下。     

Mapping of the retinal pigment epithelium in exudative age related macular degeneration

Purpose To evaluate a novel technique for three-dimensional mapping of the retinal pigment epithelium (RPE) layer in patients with subfoveal choroidal neovascularization (CNV) due to age-related macular degeneration. Methods Scanning with a recent generation retinal thickness analyzer (RTA) was performed in consecutive patients undergoing fluorescein angiography. From a 3×3mm area centered on the fovea, three-dimensional area maps of the RPE level were calculated by external spreadsheet software. Included were 18 eyes with classic CNV, 18 eyes with occult CNV and 18 eyes from age-matched normal subjects. Repeatability was assessed by measuring 17 eyes with CNV 3 times. In ten additional patients, RTA imaging results were compared with cross-sections obtained by optical coherence tomography. Results By both methods, distinctive changes in RPE level maps were observed in classic and occult CNV. In classic CNV with the lesion extending over the RPE, only focal irregularities in the anteriorly displaced RPE surface were observed. In contrast, mapping of occult CNV showed a more irregular displacement of the RPE layer. The RPE map standard deviation indicating surface irregularity differed statistically significantly between the groups, with coefficients of variance of 5.9% for controls, 6.1% for classic and 8.8% for occult CNV (P<0.001). Regarding repeatability, RPE level maps showed 1.2% coefficient of variance and an intra-class correlation coefficient of 0.87 for triplicate measurements in CNV patients. Conclusions Topographic mapping of CNV lesions offers a fast, reproducible method for obtaining three-dimensional morphometric information on the RPE level and to quantify changes.     

Intravitreal triamcinolone acetonide for exudative age-related macular degeneration among Japanese patients

AIM: To study the results of intravitreal triamcinolone acetonide (TA) for exudative age-related macular degeneration (AMD) among Japanese patients. METHODS: 13 eyes of 12 Japanese patients (9 males and 3 females) with subfoveal choroidal neovascularization (CNV) of exudative AMD received intravitreal TA (8 mg). Visual acuity, size of CNV and serous retinal detachment, and complications related to treatment were evaluated for 6 months or longer. RESULTS: Postoperative maximum visual acuity significantly improved (p < 0.05). Postoperative eyes had a greater probability of a reduced size of CNV and/or retinal detachment compared to preoperative eyes. Seven eyes showed increased intraocular pressure (21 mm Hg or over), which was controlled well by medication. Cataract development and advancement were observed in 90% of phakic eyes. No other serious complications were found. CONCLUSIONS: Intravitreal TA might be an effective treatment for subfoveal CNV of exudative AMD among Japanese as well as Caucasian patients for a comparatively short period.     

Nerve fiber layer thickness in exudative age-related macular degeneration in Japanese patients

Purpose  

To examine the peripapillary retinal nerve fiber (RNFL) thickness in Japanese patients with two major forms of exudative age-related macular degeneration (AMD), i.e., typical AMD and polypoidal choroidal vasculopathy (PCV).     

Transpupillary thermotherapy for treatment of exudative age-related macular degeneration in Japanese patients

PURPOSE: To report the therapeutic outcome of transpupillary thermotherapy (TTT) for subfoveal choroidal neovascularizarion (CNV) in brown retina using a diode-laser with the setting of lower energy level compared to the previous studies on light-pigmented Caucasian patients. METHODS: A total of 19 subfoveal CNVs in 18 patients were treated with TTT. The power of diode-laser was set 160 mW for 1.2 mm beam, 270 mW for 2.0 mm beam, and 400 mW for 3.0 mm beam, and the laser was delivered for 1 min through a slit-lamp mounted-delivery system. Patients were followed up for a mean of 8.8 months (4-12 months). Visual acuity and the fundus change as judged by funduscopic examination and simultaneous fluorescein and indocyanine green angiography were evaluated. Visual acuity was measured by a Japanese standard Landolt visual acuity chart and converted to logarithm of the minimal angle resolution (log MAR) visual acuity for statistical analysis. Improvement or decline in vision was defined as change of more than 0.2 in log MAR visual acuity. RESULTS: In eyes with minimally classic or occult only CNV, visual acuity improved in two eyes (18%) stabilized in seven eyes (64%) and worsened in two eyes (18%). In eyes with predominantly classic CNV, visual acuity improved in two eyes (25%), stabilized in four eyes (50%) and worsened in two eyes (25%). In all, 15 (84%) eyes of all studied subjects had improvement in exudation. Two (11%) and one (5%) eye(s) were noted to have a significant post-treatment haemorrhage and retinal pigment epithelial tear, respectively. CONCLUSION: In patients with brown retinal colour, the treatment outcome of TTT was comparable to that of light-pigmented Caucasian patients with approximately half the laser power energy. Further randomized control studies are warranted.     

Efficacy of intravitreal aflibercept in Japanese patients with exudative age-related macular degeneration

Purpose

To clarify the efficacy of aflibercept for treating exudative age-related macular degeneration (AMD).

Methods

We prospectively studied 47 eyes with AMD. Forty-seven patients (mean age 72.2 years) received three consecutive monthly intravitreal aflibercept injections followed by an injection every 2 months until 12 months. The primary outcome was the 12-month visual results compared with baseline; the secondary outcomes were the prevalence of geography atrophy (GA), a dry macula at month 12, and anatomic changes on optical coherence tomography.

Results

The mean logarithm of the minimum angle of resolution best-corrected visual acuity (BCVA) in 27 eyes with typical AMD and 20 eyes with polypoidal choroidal vasculopathy (PCV) significantly (p < 0.0001, p < 0.05, respectively) improved from 0.60 to 0.32 at baseline to 0.29 and 0.21 at month 12. At month 12, 22 (81.5 %) eyes with typical AMD and 17 (85 %) eyes with PCV had dry macula. The subfoveal choroidal thicknesses in typical AMD and PCV decreased significantly (p < 0.0001 for both comparisons) from 241 ± 118 and 294 ± 76 μ at baseline to 198 ± 104 and 244 ± 84 μ at month 12. Progressing or new GA was seen in three eyes with typical AMD and one eye with PCV; the mean change in the BCVA was significantly (p = 0.0026) worse at month 12. No other complications developed.

Conclusion

Intravitreal aflibercept significantly improved VA and anatomic changes in typical AMD and PCV over 12 months. Development of GA might be a risk for declining VA.

     

Clinicopathological correlation in exudative age related macular degeneration: histological differentiation between classic and occult choroidal neovascularisation

AIMS: To analyse the histopathology of classic and occult choroidal neovascular membrane surgical specimens in age related macular degeneration. METHODS: 35 membranes, from a consecutive series of surgically removed choroidal neovascular membranes in age related macular degeneration, were classified as classic or occult following the guidelines of the Macular Photocoagulation Study. Membranes with classic as well as occult components were considered as mixed membranes. The membranes were serially sectioned and stained with haematoxylin and eosin, Masson trichrome, periodic acid-Schiff, and phosphotungstic acid haematoxylin stain. The correlation has been made in a masked fashion. RESULTS: 31 membranes (19 classic, 10 occult, and two mixed membranes) could be analysed histologically. 18 classic choroidal neovascular membranes had a major subretinal fibrovascular component and 10 of these had an additional, minor fibrovascular component under the retinal pigment epithelium. The 10 occult membranes contained a fibrovascular component under the retinal pigment epithelium and the two mixed membranes contained fibrovascular tissue on both sides of the retinal pigment epithelium. Fibrin and remains of outer segments tended to occur at the lateral edges of classic membranes and to cover the inner surface of occult membranes. CONCLUSION: Classic choroidal neovascularisation in age related macular degeneration is predominantly composed of subretinal fibrovascular tissue while occult choroidal neovascularisation is composed of fibrovascular tissue at the choroidal side of the retinal pigment epithelium.     

Vitreomacular traction and exudative age‐related macular degeneration

Vitreomacular traction resulting from lacking, incomplete or anomalous posterior vitreous detachment is suspected to play a crucial role in the pathogenesis of different forms of age‐related macular degeneration (AMD) along with the known mechanisms. It is probable that the fundamental pathomechanisms of AMD formation have already begun by the time tractional forces lead to a change for the worse. Vitreomacular traction alone is perhaps not able to induce AMD. It would seem sensible to consider vitreous changes when diagnosing and treating AMD patients because of the high coincidence of vitreomacular traction and choroidal neovascularization (CNV) and the often successful treatment of other diseases of the vitreoretinal interface by vitrectomy. The concept of the pathogenesis of AMD should therefore be extended to include the influence of the vitreous, especially where therapeutic concepts such as pharmacological vitreolysis and vitreous separation have been established as causative treatment of late forms of AMD.     

Development of typical age-related macular degeneration and polypoidal choroidal vasculopathy in fellow eyes of Japanese patients with exudative age-related macular degeneration

PURPOSE: To investigate the development of typical age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) in fellow eyes of Japanese patients with exudative AMD. DESIGN: Retrospective observational consecutive case series. METHODS: Two hundred and sixteen Japanese patients were enrolled in this study from the outpatient clinic of the University of Tokyo Hospital. Ninety-one patients had typical AMD and one hundred and twenty-five patients had PCV. The average follow-up period was 33.6 and 25.1 months for typical AMD and PCV patients. RESULTS: The cumulative incidence of involvement in fellow eyes with overall exudative AMD, including both typical AMD and PCV, was 3.4% in one year, 9.3% in three years, and 11.3% in five years. It was 3.6%, 7.3%, and 11.2% in typical AMD, and 3.2%, 11.1%, and 11.1% in PCV in one, three, and five years, respectively. Before the development of exudative AMD, patients with typical AMD had a variety of funduscopic findings including retinal pigment epithelium (RPE) atrophy, drusen, drusenoid pigment epithelial detachments (PED), and normal macula. PCV patients, on the other hand, had funduscopic findings of RPE atrophy. Inner choroidal vascular abnormality of vascular network and polypoidal formation was observed in several eyes before the clinical manifestation of exudative changes. CONCLUSIONS: Typical AMD and PCV had similar probabilities of involving the fellow eye in unilaterally affected Japanese patients. RPE atrophy was a prevailing finding in fellow eyes of patients who developed PCV. In PCV, choroidal vascular network and polypoidal formation gradually grow before exudative changes.