Correlation between metamorphopsia and disorganization of the retinal inner layers in eyes with diabetic macular edema.

PURPOSE: To investigate factors associated with the severity of metamorphopsia secondary to diabetic macular edema (ME) by evaluating optical coherence tomography (OCT) parameters including disorganization of the retinal inner layers (DRIL). METHODS: We retrospectively reviewed medical records of 37 eyes of 37 consecutive patients with diabetic ME or resolved diabetic ME, who underwent spectral-domain OCT examination and metamorphopsia assessment with M-CHARTS on the same day between November 2017 and March 2018. Age, sex, visual acuity, lens status, treatment history, and factors analyzed on OCT examination including DRIL length were evaluated in association with M-CHARTS scores. RESULTS: Metamorphopsia was detected in 20 eyes (54%). The patients with metamorphopsia were relatively older than those without it (P = 0.060), and DRIL length was relatively longer in eyes with metamorphopsia (P = 0.065), while visual acuity was significantly better in eyes without metamorphopsia (P = 0.048). In correlation analyses to the severity of metamorphopsia, the DRIL length was the only OCT parameter associated with the M-CHARTS score (P = 0.035), while age, visual acuity, and ME were not significantly associated with the severity of metamorphopsia (P = 0.051, 0.060, and 0.344, respectively). CONCLUSION: The DRIL length was significantly associated with the severity of metamorphopsia secondary to diabetic ME. The inner retinal layer plays a key role in the development of metamorphopsia in eyes with diabetic ME. Metamorphopsia should be carefully considered when treating diabetic ME since its severity has been found to be independent of visual acuity and ME status.

Disorganization of the Retinal Inner Layers after Anti-VEGF Treatment for Macular Edema due to Branch Retinal Vein Occlusion.

PURPOSE: To evaluate the association between disorganization of the retinal inner layers (DRIL) and visual acuity (VA) after anti-VEGF treatment for macular edema (ME) due to branch retinal vein occlusion (BRVO). METHODS: Sixty eyes of 60 patients were retrospectively investigated. Baseline characteristics and factors analyzed on optical coherence tomography (OCT) examination at the final visit were evaluated in association with VA at the final visit. RESULTS: DRIL was detected in 39 eyes at the final visit. The central subfield thickness was significantly higher in the eyes with DRIL. While DRIL length at the final visit showed a significant association with final VA on univariable analysis, only age and ellipsoid zone disruption on OCT at the final visit were found to be significantly associated with VA on multivariable analysis. CONCLUSIONS: DRIL had only a minor role in determining VA after anti-VEGF treatment for ME due to BRVO.

Floating flap of internal limiting membrane in myopic macular hole surgery.

PURPOSE: To evaluate the surgical results of macular hole (MH) in patients with high myopia treated with pars plana vitrectomy (PPV) leaving the internal limiting membrane (ILM) flap floating in vitreous fluid at the edge of the MH. METHODS: Nine highly myopic eyes with MH of nine consecutive patients who underwent PPV were retrospectively evaluated. Three eyes were accompanied by retinal detachment (RD). ILM peeling was performed around the MH and some part of the ILM flap was left attached to the edge of the MH. Further manipulation of the ILM flap to cover the MH was not performed. Fluid-gas exchange was performed to the retinal vessel arcade level. Patients maintained a face down position for 3 to 7 days postoperatively. RESULTS: Complete MH closure was confirmed using optical coherence tomography in all eyes and three eyes with RD showed reattachment of the retina after the initial surgery. Visual acuity significantly improved (P = 0.02) and no eyes experienced MH reopening or RD occurrence during the follow-up period of 8.33 ± 3.61 months after the surgery. CONCLUSIONS: MH with or without RD in highly myopic eyes could be successfully treated with PPV leaving ILM flap floating in vitreous fluid at the edge of the MH. After the ILM peeling, further manipulation of the ILM flap to cover the MH would not be necessary for the treatment of MH in high myopia.

Outcome of primary vitrectomy in phakic patients aged younger than 50 years with rhegmatogenous retinal detachments.

PURPOSE: To evaluate the visual outcome, primary anatomic success, and cataract progression of phakic eyes of patients aged younger than 50 years treated for rhegmatogenous retinal detachment (RRD) with primary pars plana vitrectomy (PPV). METHODS: This was a retrospective, observational, cross-sectional study. The data from 53 RRD patients undergoing PPV were analyzed. The time course changes in best-corrected visual acuity (BCVA) and cataract formation were examined. RESULTS: The 53 patients had a mean age of 37.8 years. Forty-eight eyes (90.6 %) achieved anatomic success after the primary surgery. The BCVA improved significantly after surgery (mean ± SD -0.091 ± 0.146) when compared with the baseline (mean ± SD 0.214 ± 0.597; P = 0.0001). No patient aged younger than 40 years (mean 32.5 years; range 17-39) developed significant lens opacity or received cataract surgery within the first 3 years. Of the patients aged older than 40 years (mean 43.8 years; range 40-49), 22 % developed significant lens opacity and received cataract surgery within the first 3 years. A significant difference was found in cataract progression between the two groups within the first 3 years (P = 0.0217), but not over the entire follow-up period (P = 0.1679). CONCLUSIONS: We found that lens-sparing PPV for RRD in patients aged younger than 50 years had a reasonable success rate, although cataract progression was evident during the follow-up period in patients aged older than 40 years.

A comparison of patient pain and visual outcome using topical anesthesia versus regional anesthesia during cataract surgery.

PURPOSE: The purpose of this study was to compare the level of patient pain during the phacoemulsification and implantation of foldable intraocular lenses while under topical, intracameral, or sub-Tenon lidocaine. PATIENTS AND METHODS: This was a retrospective study. Three hundred and one eyes subjected to cataract surgery were included in this study. All eyes underwent phacoemulsification surgery and intraocular lens implantation using topical, sub-Tenon, or intracameral anesthesia. The topical group received 4% lidocaine drops, and the intracameral group received a 0.1-0.2 cc infusion of 1% preservative-free lidocaine into the anterior chamber through the side port combined with topical drops of lidocaine. The sub-Tenon group received 2% lidocaine. Best-corrected visual acuity, corneal endothelial cell loss, and intraoperative pain level were evaluated. Pain level was assessed on a visual analog scale (range 0-2). RESULTS: There were no significant differences in visual outcome and corneal endothelial cell loss between the three groups. The mean pain score in the sub-Tenon group was significantly lower than that in the topical and intracameral groups (P=0.0009 and P=0.0055, respectively). In 250 eyes without high myopia (< -6D), there were no significant differences in mean pain score between the sub-Tenon and intracameral groups (P=0.1417). No additional anesthesia was required in all groups. CONCLUSION: Intracameral lidocaine provides sufficient pain suppressive effects in eyes without high myopia, while sub-Tenon anesthesia is better for cataract surgery in eyes with high myopia.

Alternaria extract activates autophagy that induces IL-18 release from airway epithelial cells.

Alternaria alternata is a major outdoor allergen that causes allergic airway diseases. Alternaria extract (ALT-E) has been shown to induce airway epithelial cells to release IL-18 and thereby initiate Th2-type responses. We investigated the underlying mechanisms involved in IL-18 release from ALT-E-stimulated airway epithelial cells. Normal human bronchial epithelial cells and A549 human lung adenocarcinoma cells were stimulated with ALT-E in the presence of different inhibitors of autophagy or caspases. IL-18 levels in culture supernatants were measured by ELISA. The numbers of autophagosomes, an LC3-I to LC3-II conversion, and p62 degradation were determined by immunofluorescence staining and immunoblotting. 3-methyladenine and bafilomycin, which inhibit the formation of preautophagosomal structures and autolysosomes, respectively, suppressed ALT-E-induced IL-18 release by cells, whereas caspase 1 and 8 inhibitors did not. ALT-E-stimulation increased autophagosome formation, LC-3 conversion, and p62 degradation in airway epithelial cells. LPS-stimulation induced the LC3 conversion in A549 cells, but did not induce IL-18 release or p62 degradation. Unlike LPS, ALT-E induced airway epithelial cells to release IL-18 via an autophagy dependent, caspase 1 and 8 independent pathway. Although autophagy has been shown to negatively regulate canonical inflammasome activity in TLR-stimulated macrophages, our data indicates that this process is an unconventional mechanism of IL-18 secretion by airway epithelial cells.

IL-33 enhanced the proliferation and constitutive production of IL-13 and IL-5 by fibrocytes.

Interleukin-33 appears to play important roles in the induction of allergic airway inflammation. However, whether IL-33 is involved in airway remodeling remains unclear. Because fibrocytes contribute to tissue remodeling in the setting of chronic inflammation, we examined the effects of IL-33 on fibrocyte functions. Fibrocytes were generated in vitro from peripheral blood mononuclear cells by culturing in the presence of platelet derived growth factors and the cells were stimulated with IL-33. IL-33 enhanced cell proliferation, α-SMA expression, and pro-MMP-9 activity by the fibrocytes without increasing endogenous transforming growth factor-ß1 production. Fibrocytes constitutively expressed IL-13 and IL-5, and their production was augmented by stimulation with IL-33. Dexamethasone inhibited the functions of fibrocytes, but IL-33 made fibrocytes slightly refractory to the inhibitory effect of dexamethasone in terms of IL-13 production. Montelukast suppressed IL-13 production by nonstimulated fibrocytes but not those stimulated by IL-33. These findings suggest that IL-33 is involved in the airway remodeling process through its modulation of fibrocyte function independent of antigen stimulation. IL-33 might partially reduce the therapeutic effects of glucocorticoid and cysteinyl leukotriene receptor antagonist on fibrocyte-mediated Th2 responses.

Efficacy of inverted internal limiting membrane flap technique for the treatment of macular hole in high myopia.

PURPOSE: To determine the effect of pars plana vitrectomy (PPV) with inverted internal limiting membrane (ILM) flap technique for macular hole with or without retinal detachment in highly myopic eyes. DESIGN: Retrospective, interventional case series. METHODS: Ten eyes of 10 patients with macular hole with (4 eyes) or without (6 eyes) retinal detachment in high myopia (axial length more than 26.5 mm) were treated by PPV with inverted ILM flap technique. RESULTS: Macular hole closure was observed in 8 eyes (80%) following the initial surgery (in 5 eyes without retinal detachment and in 3 eyes with retinal detachment). In 4 eyes with retinal detachment caused by macular hole, retinas of 3 eyes were reattached by the initial surgery. Postoperative best-corrected visual acuity improved by more than 2 lines in 5 eyes (50%), was unchanged in 4 eyes (40%), and worsened by more than 2 lines in 1 eye (10%). CONCLUSIONS: Inverted ILM flap technique might contribute to a high closure rate of macular hole and be a preferable adjuvant to the treatment of macular hole in high myopia with or without retinal detachment.

IL-17A/F modulates fibrocyte functions in cooperation with CD40-mediated signaling.

T helper 17 (Th17) cells that produce interleukin (IL)-17A and IL-17F have been found to participate in the development of bronchial asthma and bleomycin-induced pulmonary fibrosis. However, whether they play a causative role in the airway remodeling observed in these respiratory diseases remains unclear. Because fibrocytes are involved in tissue repair and fibrosis and are presumably precursors of lung fibroblasts and myofibroblasts, we examined the effects of IL-17A/F on fibrocyte functions. Both IL-17A and IL-17F enhanced fibrocytes' α-smooth muscle actin expression. Priming fibrocytes with IL-17A enhanced their CD40-mediated IL-6 production, whereas IL-17F-priming increased the CD40-mediated mRNA expression of collagen I, vascular endothelial growth factor, and angiogenin. CD4(+) T cells co-cultured with fibrocytes produced IL-17A, which was inhibited by blocking CD40 and CD40 ligand interactions. These findings suggest that cooperative interactions between fibrocytes and Th17 cells play an important role via CD40- and IL-17A/F-mediated signaling for collagen and proangiogenic factor production, which may lead to the extracellular matrix deposition and neovascularization seen in airway remodeling.

Association of ARMS2 genotype with bilateral involvement of exudative age-related macular degeneration.

PURPOSE: To study the association of ARMS2 A69S genotype with the development of exudative age-related macular degeneration (AMD) in the unaffected fellow eye and to estimate the duration until the development of AMD in the second eye. DESIGN: Retrospective cohort study. METHODS: We retrospectively reviewed 326 patients who had exudative AMD in at least 1 eye, genotyping of ARMS2 A69S, and a minimum follow-up of 2 years. Survival analysis and Cox proportional hazard regression analysis were used to examine the association between candidate factors and the duration until the development of AMD in the second eye. RESULTS: One hundred nineteen patients (36.5%) had bilateral exudative AMD at the initial visit. A risk allele of ARMS2 A69S was more frequently seen in patients with bilateral AMD (P = .0270) than in those with unilateral AMD. Of the 207 unilateral AMD patients, 23 (11.1%) had AMD in the fellow eye after a mean duration of 56.3 ± 40.4 months. Fellow-eye involvement was associated with ARMS2 A69S genotype (hazard ratio [HR], 2.673; P = .0013), age (HR, 1.102; P = .0005), and smoking history (HR, 0.680; P = .3663). As HRs indicate, correlation of genotype (2.673) was as high as that of 10-year aging (1.102(10) = 2.641). Survival analysis revealed that patients with risk homozygous (TT) genotype had second-eye involvement significantly earlier than those with other genotypes (P = .0028). When the observation duration reached 120 months, second-eye involvement had developed in 50%, 6.6%, and 11.2% of the TT, GT, and GG cohorts, respectively. CONCLUSION: ARMS2 A69S genotype is associated with second-eye involvement of exudative AMD and with the period between first- and second-eye involvements.

Significance of C2/CFB variants in age-related macular degeneration and polypoidal choroidal vasculopathy in a Japanese population.

PURPOSE: To determine whether genetic variants in the complement component 2 and factor B gene (C2/CFB) locus are associated with the risk for typical age-related macular degeneration (AMD) or polypoidal choroidal vasculopathy (PCV) in a Japanese population. METHODS: Four single nucleotide polymorphisms (SNPs) were genotyped across the C2/CFB locus of patients with typical AMD (n = 455) or PCV (n = 581) and of 865 controls. Differences in the observed genotypic distribution between the case and control groups were tested by logistic regression analysis for age and sex adjustments. Significant associations were confirmed using a second control group of 336 cataract patients. A further model adjusting for age-related maculopathy susceptibility 2 (ARMS2) A69S, complement factor H (CFH) I62V, age, sex and smoking status was performed, to confirm their independent association from other covariates. RESULTS: C2 rs547154 and CFB rs541862 were significantly associated with typical AMD and PCV in this Japanese sample (P < 0.05). These two SNPs were also significantly associated with typical AMD and PCV in evaluation of the second control cohort (P < 0.05). Furthermore, an independent association of C2/CFB variants was found for both typical AMD and PCV with age, sex, smoking, and genetic background of ARMS2 A69S and CFH I62V (vs. typical AMD: P = 0.0073, odds ratio [OR] = 0.47; vs. PCV: P = 0.0083, OR = 0.53). CONCLUSIONS: C2/CFB variants play a protective role in the risk of developing neovascular AMD and PCV in the Japanese.

Association of lesion size and visual prognosis to polypoidal choroidal vasculopathy.

PURPOSE: To investigate the progression of vascular lesions of polypoidal choroidal vasculopathy (PCV) as viewed with indocyanine green angiography and the visual prognosis of these eyes. DESIGN: Retrospective case study. METHODS: We reviewed retrospectively the medical records of 88 consecutive patients (88 eyes) with PCV who had been examined with indocyanine green angiography for more than 2 years. RESULTS: Depending on the initial area of the vascular lesion, eyes were divided into smaller PCV (baseline area of lesion being < 1 disc area [DA], n = 22) and larger PCV (baseline area of lesion being ≥ 1 DA, n = 66). In larger PCV, the mean area of the lesion progressed significantly from 6.49 ± 8.96 mm(2) to 16.27 ± 14.19 mm(2) (P < .0001) with marked deterioration of visual acuity (P < .0001) during follow-up. In contrast, smaller PCV often showed minimal progression of the lesion, only limited exudative change, and the eyes maintained their initially good vision to the final visit. Smaller PCV lesions rarely progressed to extensive PCV lesions. Severe vision-threatening complications (ie, suprachoroidal hemorrhage, vitreous hemorrhage, and tears of the retinal pigment epithelium) were seen only in eyes with larger PCV, and in studying single nucleotide polymorphisms A69S of ARMS2 genes, there was a significant difference in T allele frequency between individuals with smaller PCV and those with larger PCV (20.2% vs 79.8%; P = .0235). CONCLUSIONS: PCV with small vascular lesions shows minimal progression and no vision-threatening complications, and these eyes often maintain good visual acuity for a long time.

Association between the SERPING1 gene and age-related macular degeneration and polypoidal choroidal vasculopathy in Japanese.

PURPOSE: Recently, a complement component 1 inhibitor (SERPING1) gene polymorphism was identified as a novel risk factor for age-related macular degeneration (AMD) in Caucasians. We aimed to investigate whether variations in SERPING1 are associated with typical AMD or with polypoidal choroidal vasculopathy (PCV) in a Japanese population. METHODS: We performed a case-control study in a group of Japanese patients with typical AMD (n = 401) or PCV (n = 510) and in 2 independent control groups--336 cataract patients without age-related maculopathy and 1,194 healthy Japanese individuals. Differences in the observed genotypic distribution between the case and control groups were tested using chi-square test for trend. Age and gender were adjusted using logistic regression analysis. RESULTS: We targeted rs2511989 as the haplotype-tagging single nucleotide polymorphism (SNP) for the SERPING1 gene, which was reported to be associated with the risk of AMD in Caucasians. Although we compared the genotypic distributions of rs2511989 in typical AMD and PCV patients against 2 independent control groups (cataract patients and healthy Japanese individuals), SERPING1 rs2511989 was not significantly associated with typical AMD (P = 0.932 and 0.513, respectively) or PCV (P = 0.505 and 0.141, respectively). After correction for age and gender differences based on a logistic regression model, the difference in genotypic distributions remained insignificant (P>0.05). Our sample size had a statistical power of more than 90% to detect an association of a risk allele with an odds ratio reported in the original studies for rs2511989 for developing AMD. CONCLUSIONS: In the present study, we could not replicate the reported association between SERPING1 and either neovascular AMD or PCV in a Japanese population; thus, the results suggest that SERPING1 does not play a significant role in the risk of developing AMD or PCV in Japanese.

Genetic variants in pigment epithelium-derived factor influence response of polypoidal choroidal vasculopathy to photodynamic therapy.

PURPOSE: To investigate whether photodynamic therapy (PDT) outcomes of polypoidal choroidal vasculopathy (PCV) are related to baseline clinical characteristics, smoking history, or genetic factors by analyzing the retreatment-free period after the first PDT. DESIGN: Retrospective cohort study. PARTICIPANTS: The study consisted of 167 patients with PCV who underwent PDT as their first treatment. METHODS: We targeted 638 single nucleotide polymorphisms (SNPs) in 42 possible susceptible genes for age-related macular degeneration to evaluate their relation to the effectiveness of PDT for PCV. For this evaluation, we used 2 methods: (1) survival analysis, with the retreatment-free period as the target; and (2) logistic regression test between the need for additional therapy within 3 months after the first PDT and the genotypes, with age, gender, smoking status, and greatest linear dimension (GLD) at baseline as covariates. The contributions of smoking status and GLD at baseline for the retreatment-free period also were evaluated. Contributions of these factors to visual prognosis were evaluated for 1 year after PDT. MAIN OUTCOME MEASURES: Retreatment-free period after the first PDT for PCV. Secondary outcome measures included correlation of the susceptible factor to the retreatment requirement within the 3-month follow-up and the mean visual acuity change. RESULTS: In survival analyses, SERPINF1 rs12603825 showed a significant association with the retreatment-free period after the first PDT; those patients homozygous for the minor allele A of rs12603825 received additional treatment after PDT within significantly shorter times than those with other genotypes (P = 0.0038). There was no significant difference in the retreatment-free period between baseline GLD and smoking status. Retreatment within 3 months was required significantly more in patients with the AA genotype, even after taking into consideration the effect of clinical characteristics (age, gender), baseline PCV lesion size, and smoking status (P = 0.0027). Furthermore, patients with the AA genotype showed significantly worse visual prognosis after PDT (P = 0.013). CONCLUSIONS: Pigment epithelium-derived factor (SERPINF1 or PEDF) polymorphisms may influence the initial response to and visual prognosis after PDT for PCV. Our findings may lead to understanding the pathogenesis of PCV and modification of the effects of PDT.

Geographic pattern of central retinal sensitivity after intravitreal triamcinolone for diabetic macular edema.

PURPOSE: To evaluate the geographic pattern of central retinal sensitivity and its resolution shortly after intravitreal injection of triamcinolone acetonide (IVTA) for diabetic macular edema (DME). METHODS: Twenty eyes of 20 patients who underwent IVTA for the treatment of DME were reviewed retrospectively. Early changes in best-corrected visual acuity (BCVA), central macular thickness (CMT), photoreceptor inner and outer segments (IS/OS) line and central retinal sensitivity were analyzed. Retinal sensitivity was measured at 40 points within the central 10 degrees of the macula with the Micro Perimeter 1 before treatment, and at 1 week and 1 month after IVTA. RESULTS: Mean BCVA and CMT improved significantly at 1 week and 1 month after IVTA. Mean retinal sensitivity, however, showed no significant improvement at 1 week (P = 0.238), but did show significant improvement at 1 month (P = 0.0003). Mean retinal sensitivity of the points at the central 2 degrees, which was significantly lower than that at 6 and 10 degrees before treatment, showed improvement similar to those of 6 and 10 degrees after IVTA. Mean retinal sensitivity in the nasal quadrant of the macular area had the best sensitivity at all time points, and improved more than it did in the other quadrants. Mean retinal sensitivity in the central 2 degrees was better in the eyes with complete IS/OS line (P < 0.0001). CONCLUSIONS: BCVA and CMT improved significantly after IVTA for DME. Retinal sensitivity also showed significant, albeit relatively slow, improvement. The nasal quadrant of the macular area showed more improvement than did any other quadrant.

Joint effect of cigarette smoking and CFH and LOC387715/HTRA1 polymorphisms on polypoidal choroidal vasculopathy.

PURPOSE: To investigate whether the major genetic and environmental risk factors of age-related macular degeneration (AMD)-CFH Y402H and LOC387715 A69S and cigarette smoking-are also associated with polypoidal choroidal vasculopathy (PCV) and whether the associations of CFH Y402H and LOC387715 A69S with PCV are modified by smoking. METHODS: Three hundred seventy-five Japanese patients with PCV and 847 Japanese who served as population-based control subjects, all ≥55 years of age, were studied. CFH Y402H (rs1061170) and LOC387715 A69S (rs10490924) were genotyped with a single-nucleotide polymorphism (SNP) assay. An unconditional logistic regression model was used to analyze the association between age, sex, smoking status, CFH Y402H, LOC387715 A69S, and PCV. The synergy index (SI) was measured to assess gene-smoking and gene-gene interaction as a departure from additivity. RESULTS: CFH Y402H, LOC3387715 A69S, and cigarette smoking status were all significantly associated with PCV; for CFH Y402H, the adjusted odds ratio (OR) for the number of copies of the allele was 1.63 (95% confidence interval [CI], 1.12-2.36; P < 0.05); for LOC387715 A69S, the adjusted OR was 2.26 (95% CI, 1.83-2.78; P < 0.0001); and for smoking status (ever versus never smoked), the adjusted OR was 1.45 (95% CI, 1.00-2.10; P < 0.05). The joint effect of CFH Y402H and smoking was significantly greater than the additive scale, with an SI of 2.41 (95% CI, 1.14-5.10). CONCLUSIONS: CFH Y402H and LOC387715 A69S are both significantly associated with PCV. Cigarette smoking is an environmental risk factor for PCV. The findings suggest interactions between CFH 402H and cigarette smoking in PCV.

CFH and ARMS2 variations in age-related macular degeneration, polypoidal choroidal vasculopathy, and retinal angiomatous proliferation.

PURPOSE: To seek an association in Japanese individuals between the CFH polymorphisms Y402H and I62V and the ARMS2 polymorphism A69S and age-related macular degeneration (AMD) or its three subtypes: typical (t)AMD, polypoidal choroidal vasculopathy (PCV), and retinal angiomatous proliferation (RAP). METHODS: The three polymorphisms were genotyped in a case-control study of 1351 control subjects and 962 patients with AMD. RESULTS: The three polymorphisms correlated with AMD (Y402H, P = 1.54 × 10(-6); I62V, P =1.94 × 10(-29); and A69S, P = 9.56 × 10(-43)). The I62V and A69S polymorphisms were associated with all three subtypes: tAMD (P = 3.74 × 10(-18) and 1.37 × 10(-35), respectively), PCV (P = 3.18 × 10(-19) and 3.96 × 10(-18), respectively), and RAP (P = 0.034 and 2.49 × 10(-18), respectively). Y402H was associated with tAMD (P = 3.00 × 10(-5)) and with PCV (P = 9.73 × 10(-5)), but no association was found with RAP, possibly because of the small sample size and the rare minor allele. The risk allele contribution of A69S was stronger for RAP than for tAMD or PCV and was stronger for tAMD than for PCV. CONCLUSIONS: CFH Y402H is associated with AMD, tAMD, and PCV, whereas I62V is associated with all three subtypes. ARMS2 A69S has a strong association with all three subtypes, with the association being strongest for RAP and weakest for PCV. PCV and RAP may thus be subtypes of AMD that are genetically distinct from tAMD.

Lamellar macular hole formation in patients with diabetic cystoid macular edema.

PURPOSE: To report lamellar macular hole formation in four patients with diabetic cystoid macular edema (CME). METHODS: A review of the medical records of four patients with diabetic CME in whom lamellar macular hole formation was observed. The morphologic changes of CME, seen using optical coherence tomography (OCT), and best-corrected visual acuity were evaluated. RESULTS: Lamellar macular hole formation had occurred, as determined by slit-lamp biomicroscopy and OCT. Although the inner retinal layer had disappeared, the outer retinal layer was preserved. On OCT, the reflective line of an epiretinal membrane or a posterior hyaloid membrane was seen on the surface of juxtafoveal retina, and visual acuity remained unchanged in all four patients. CONCLUSION: In diabetic patients with CME, the CME occasionally changes spontaneously to a lamellar macular hole. Although the central cystoid space disappears and foveal thickness decreases after this transformation, visual acuity may be little affected as long as the structure of the outer retina remains intact.

ARMS2 (LOC387715) variants in Japanese patients with exudative age-related macular degeneration and polypoidal choroidal vasculopathy.

PURPOSE: To determine the characteristics of the polymorphisms in the ARMS2 gene in Japanese patients with age-related macular degeneration (AMD) and those with polypoidal choroidal vasculopathy (PCV) and in healthy controls, and also to show possible associations of the polymorphisms with the disease. DESIGN: Case-control association study. METHODS: Fifty-six unrelated Japanese individuals with AMD, 55 with PCV, and 77 controls were studied. The most common polymorphism in the ARMS2 gene on chromosome 10 was resequenced. Association tests were performed for inferred haplotypes. RESULTS: A total of 22 polymorphisms were identified, and 13 were shared with those in White persons with AMD. The sequence of the deletion-and-insertion polymorphism, de1443ins54, a functional polymorphism causing an instability of the messenger ribonucleic acid of ARMS2 in the Japanese, did not differ from that in White persons. Among the polymorphisms seen in the White population, rs10490923 (R3H) as well as 7 other polymorphisms were not observed in the Japanese. One haplotype, which contained the T allele of the rs10490924 (A69S) and the variant of de1443ins54 polymorphism, had an odds ratio of 3.14 (P = 7.8 x 10(-6)) for AMD and 2.00 (P = .0058) for PCV. Among the 9 polymorphisms that were unique to the Japanese population, 2 had a minor allelic frequency of more than 0.05, and these 2 polymorphism were included as nonrisk haplotypes. CONCLUSIONS: The de1443ins54 polymorphism is a common variant between White and Japanese populations. It is strongly associated not only with AMD but also with PCV.

Association between foveal photoreceptor integrity and visual outcome in neovascular age-related macular degeneration.

PURPOSE: To evaluate the correlation between visual outcome and foveal photoreceptor integrity after successful treatment of eyes with neovascular age-related macular degeneration (AMD). DESIGN: Retrospective chart review. METHODS: We retrospectively studied the medical records of 51 eyes of 51 patients with neovascular AMD who were treated successfully with photodynamic therapy (PDT). All eyes were followed-up for more than 24 months after the initial treatment. Using spectral-domain optical coherence tomography, the status of the inner segment and outer segment (IS/OS) photoreceptor junction was assessed as a hallmark of the integrity of the foveal photoreceptor layer. RESULTS: At the final visit, no eyes showed an exudative change. A complete or discontinuous IS/OS line was detected beneath the fovea in 8 (15.7%) and 25 (29.4%) eyes, respectively, whereas 28 (54.9%) had no IS/OS line. Eyes with a continuous or discontinuous IS/OS line beneath the fovea had better final visual acuity (VA) than did eyes without an IS/OS line (P < .001, respectively). Of the 51 eyes, 36 showed polypoidal choroidal vasculopathy (PCV), whereas 15 were diagnosed as having typical AMD without PCV. Visual outcome was significantly better in eyes with PCV (P = .026). Most eyes (13/15; 86.7%) with typical AMD had no IS/OS line at the final visit, whereas only 13 (36.1%) of the 36 eyes with PCV had no IS/OS line beneath the fovea. CONCLUSIONS: Integrity of the photoreceptor layer beneath the fovea is associated with the final VA in neovascular AMD after successful PDT.