Genome-wide association study suggests four variants influencing outcomes with ranibizumab therapy in exudative age-related macular degeneration.

To identify factors associated with ranibizumab responses in patients with exudative age-related macular degeneration (AMD), we performed a genome-wide association study (GWAS) and a replication study using a total of 919 exudative AMD patients treated with intravitreal ranibizumab in a Japanese population. In the combined analysis of GWAS and the replication study, no loci reached genome-wide significant level; however, we found four variants showed suggestive level of associations with visual loss at month three (rs17822656, rs76150532, rs17296444, and rs75165563: Pcombined < 1.0 × 10-5). Of the candidate genes within these loci, three were relevant to VEGF-related pathway (KCNMA1, SOCS2, and OTX2). The proportions of patients who worsened visual acuity were 13.7%, 38.8%, 58.0%, and 80.0% in patients with 0, 1, 2, and 3 or more identified risk variants, respectively. Changes in visual acuity decreased linearly as the number of risk variants increased (P = 1.67 × 10-12). The area under the curve using age, baseline visual acuity, and history of previous treatment was 0.607, and improved significantly to 0.713 in combination with identified variants (P < 0.0001). Although further study is needed to confirm their associations, our results offer candidate variants influencing response to ranibizumab therapy.

Postoperative roll cake-like macular fold after retinal detachment surgery.

PURPOSE: To report a case developing a severe retinal fold (RF), resembling a roll cake on optical coherence tomography (OCT), after retinal detachment (RD) surgery. CASE REPORT: A 61-year-old man underwent vitrectomy for a limited macula-on-superior rhegmatogenous RD and gas tamponade at another hospital. Despite remaining prone for 4 days, RF was noted after gas disappearance and he was referred to us. OCT showed a roll cake-like RF, which resolved after vitrectomy with internal limiting membrane (ILM) peeling, creation of a new detachment, perfluorocarbon liquid injection, air-fluid exchange, silicone oil tamponade and prone positioning. CONCLUSION: ILM peeling including the area of the retinal fold, followed by new detachment creation and finally perfluorocarbon liquid injection, effectively flattened the severe RF. To our knowledge, this is the most severe case of RF to be documented by OCT and illustrates that broad ILM peeling, including the RF, is effective for treating RF.

Comparison of pro re nata versus Bimonthly Injection of Intravitreal Aflibercept for Typical Neovascular Age-Related Macular Degeneration.

PURPOSE: The aim of this study was to clarify the 1-year outcomes of pro re nata (PRN) and bimonthly intravitreal injections of aflibercept (IVA) for typical neovascular age-related macular degeneration (tAMD) after the initial 3 monthly IVA. METHODS: We conducted a prospective, interventional study. Fifty-eight treatment-naïve patients with tAMD were randomly assigned to the PRN (30 patients) or the bimonthly (28 patients) treatment group. Both groups initially received 3 monthly IVA. Visual acuity, central macular retinal thickness (CRT), and central choroidal thickness (CCT) were evaluated at 12 months. Subanalysis was performed to identify factors associated with the best-corrected visual acuity (BCVA). RESULTS: BCVA was significantly improved only in the bimonthly group at 12 months. CRT and CCT were significantly decreased in both groups. Subanalysis showed that the only factor associated with BCVA improvement at 12 months was the existence of pigment epithelial detachment at baseline. CONCLUSIONS: BCVA showed significant improvement only in the bimonthly group but not in the PRN group at 12 months.

A Multicenter Randomized Controlled Study of Antioxidant Supplementation with Lutein for Chronic Central Serous Chorioretinopathy.

PURPOSE: To investigate functional and morphological changes in patients with chronic central serous chorioretinopathy after supplementation with antioxidants containing lutein or a placebo. PROCEDURES: One hundred eyes of 100 patients were randomly divided into 2 groups, one taking tablets with lutein plus other antioxidants and the other taking a placebo for 6 months. Best-corrected visual acuity (BCVA) and the subfoveal fluid height on optical coherence tomography were measured. RESULTS: Seventy-nine patients (37 in the supplementation and 42 in the placebo group) completed the 6-month follow-up. In the supplementation group, mean BCVA showed significant improvement (p = 0.003), while there was no significant change in the placebo group (p = 0.589). The mean subfoveal fluid height was significantly reduced, by 28.6%, in the supplementation group (p = 0.028), in contrast to 3.3% in the placebo group (p = 0.898). CONCLUSIONS: Antioxidant supplementation significantly reduced subfoveal fluid height. The impacts of antioxidant supplementation on BCVA remain to be elucidated in future studies.

Intravitreal Tissue Plasminogen Activator, Ranibizumab, and Gas Injection for Submacular Hemorrhage in Polypoidal Choroidal Vasculopathy.

PURPOSE: To investigate the efficacy of intravitreal injection of recombinant tissue plasminogen activator (rt-PA), ranibizumab, and gas without vitrectomy for submacular hemorrhage. DESIGN: Prospective, interventional, consecutive case series. PARTICIPANTS: Twenty consecutive patients (20 eyes) with submacular hemorrhage secondary to exudative age-related macular degeneration (AMD) or polypoidal choroidal vasculopathy (PCV). METHODS: Ranibizumab, rt-PA (25 µg/0.05 ml), and 100% perfluoropropane (0.3 ml) were injected intravitreally, followed by 2-day prone positioning. MAIN OUTCOME MEASURES: The primary outcome measure was best-corrected visual acuity (BCVA) 6 months after treatment. Secondary outcome measures included central retinal thickness (CRT), central pigment epithelial detachment (PED) thickness, central ellipsoid zone, recurrence rate, and complications. RESULTS: Underlying disease was exudative AMD in 1 eye and PCV in 19 eyes. Submacular hemorrhage ranged in size from 2 to 31 disc diameters. Complete displacement of submacular hemorrhage was achieved in 17 eyes (85%), and partial displacement was achieved in 3 eyes (15%). Snellen BCVA improved from 20/139 before treatment to 20/65 at 6 months (P = 0.0061). Mean change in Early Treatment Diabetic Retinopathy Study score from baseline was +13 letters (P = 0.0040). Mean CRT decreased from 599 µm before treatment to 208 µm at 6 months (P < 0.0001), and central PED thickness decreased from 188 to 88 µm (P = 0.0140). Three eyes developed vitreous hemorrhage, and 1 eye developed retinal detachment; all were treated surgically, and Snellen BCVA improved at 6 months (P = 0.0012). Recurrence was observed in 10 eyes (50%) within 6 months, but visual acuity was preserved with intravitreal injection of anti-vascular endothelial growth factor (VEGF) pro re nata (PRN). The factors that affect BCVA at 6 months after treatment were pre- and posttreatment central ellipsoid zone (P = 0.0366 and P = 0.0424), pretreatment BCVA (P = 0.0015), and pre- and posttreatment central PED thickness (P = 0.0046, P = 0.0021). CONCLUSIONS: Subretinal hemorrhage treatment by intravitreal injection of rt-PA, ranibizumab, and gas is useful to achieve hemorrhage displacement and lesion improvement. To preserve visual acuity, early detection of posttreatment recurrence and intravitreal anti-VEGF injection PRN are necessary.

EXPERIMENTAL VISUALIZATION AND QUANTIFICATION OF VITREOUS CONTAMINATION FOLLOWING INTRAVITREAL INJECTIONS.

PURPOSE: To detect and quantify vitreous contamination after intravitreal injection using an experimental vitreous contamination model. METHODS: Enucleated porcine eyes served as a Type 1 experimental vitreous contamination model with fluoresbrite carboxylate microspheres applied to the conjunctival surface. Saline solution (0.05 mL) was injected using a 27-, 30-, or 32-gauge (G) needle. Injection procedures were monitored using an intraocular fiber catheter. Condensed microspheres were applied to an excised sheet of porcine sclera (Type 2 experimental vitreous contamination model). Saline solution (0.05 mL) was injected from the top of an applied condensed microsphere through the sclera using a needle of one of the aforementioned gauges, and samples were then collected. The fluorescence strength of samples was measured using fluorophotometry. RESULTS: We visually detected fluorescent microspheres in 10/10, 9/10, and 9/10 eyes injected with 27-G, 30-G, and 32-G needles, respectively. In the experimental quantification study, values at all needle gauges were significantly higher than those of controls (P < 0.01). Fluorescence strength was significantly higher in the 27-G group than in the 30- (P < 0.01) and 32-G (P < 0.01) groups. CONCLUSION: Intravitreal injection carries the risk of introducing contamination directly into the eyes even when a 32-G needle is used. Furthermore, the 27-G needle carries the highest contamination risk.

Findings of Optical Coherence Tomographic Angiography at the Choriocapillaris Level in Central Serous Chorioretinopathy.

PURPOSE: To reveal vascular signals at the choriocapillaris level in central serous chorioretinopathy (CSC) using optical coherence tomographic angiography (OCTA). PROCEDURES: We analyzed vascular signals at the choriocapillaris level in 58 CSC and 51 contralateral eyes by OCTA (RTVue XR Avanti with AngioVue; Optovue Inc., Fremont, Calif., USA). Data analysis included age, best corrected visual acuity (BCVA), disease duration and serous retinal detachment (SRD) height. RESULTS: Morphologically, abnormal signals at the choriocapillaris level were detected in all CSC eyes (100%), and then classified into three patterns. Age, BCVA, disease duration and SRD height showed no significant correlation with signal patterns. Thirty-one contralateral eyes (61%) showed abnormal signals at the choriocapillaris level on OCTA, while 20 (39%) had a normal pattern. CONCLUSIONS: OCTA revealed three types of abnormal signals not only in CSC eyes but also in fellow eyes without SRD. OCTA may provide information for elucidating the underlying pathogenesis of CSC.

Investigation of the Etiology of Central Serous Chorioretinopathy Using En-Face Optical Coherence Tomography and Indocyanine Green Angiography.

PURPOSE: To identify locations of hypofluorescent lesions on late-phase indocyanine green angiography (ICGA) in patients with central serous chorioretinopathy (CSC) using en-face optical coherence tomography (OCT). PROCEDURES: We retrospectively studied 25 consecutive untreated CSC patients, using swept-source OCT and ICGA. En-face swept-source OCT images were automatically segmented and flattened with Bruch's membrane (BrM). We compared the sizes of hyperreflective areas in the 25 CSC and 25 contralateral eyes on en-face images and hypofluorescent areas on ICGA after 30 min. RESULTS: All 25 CSC eyes and 13 contralateral eyes showed abnormal hypofluorescent areas on late-phase ICGA and hyperreflective areas on en-face OCT from BrM to the choriocapillaris, and these findings correlated with the abnormal areas (r = 0.9988; p < 0.001). CONCLUSIONS: In CSC patients, we detected abnormal hypofluorescence on ICGA in the late phase, which corresponded to abnormal hyperreflective areas from BrM to the choriocapillaris level in en-face images.

Characteristics of Hyperautofluorescent Choroidal Vessels within the Macular Atrophic Area Using Spectral-Domain Optical Coherence Tomography.

PURPOSE: The aim of this study was to clarify the characteristic findings in patients with geographic atrophy with or without hyperautofluorescent choroidal vessels within macular atrophic areas on short-wavelength fundus autofluorescence imaging. PROCEDURES: Sixty-seven eyes of 43 consecutive patients with macular atrophic areas were divided into groups with (group 1) and without (group 2) hyperautofluorescent choroidal vessels on fundus autofluorescence imaging and then retrospectively studied using spectral-domain optical coherence tomography. RESULTS: In group 1 (n = 21), the average subfoveal choroidal thickness was 61.5 ± 20.1 µm, and the average foveal retinal thickness was 93.0 ± 51.3 µm. On the other hand, in group 2 (n = 46), the average subfoveal choroidal thickness was 200.7 ± 83.1 µm, and the average foveal retinal thickness was 109.2 ± 58.5 µm. Although retinal thickness did not differ significantly between the two groups (p = 0.28), the difference in choroidal thickness was statistically significant (p < 0.001). CONCLUSIONS: Choroidal thinning might contribute to the hyperautofluorescence of choroidal vessels.

One-year outcomes with half-dose verteporfin photodynamic therapy for chronic central serous chorioretinopathy.

PURPOSE: To assess the 1-year outcome of half-dose verteporfin photodynamic therapy (PDT) for patients with chronic central serous chorioretinopathy (CSC). DESIGN: Retrospective, interventional case series with no controls. PARTICIPANTS: A total of 204 eyes of 204 patients with chronic CSC were studied. METHODS: Fluorescein angiography (FA) and indocyanine green angiography (ICGA) were performed before PDT. The best-corrected visual acuities (BCVAs) were measured and optical coherence tomography was performed before and 1, 3, 6, 9, and 12 months after PDT. MAIN OUTCOME MEASURES: The main outcome measures were the resolution of the serous retinal detachment (SRD), changes in BCVA, and ocular and systemic complications at 12 months. RESULTS: A total of 182 of 204 eyes (89.2%) had complete resolution of the SRD at 12 months after the PDT. Eleven eyes (5.4%) had a persistent SRD throughout the follow-up period, and 12 eyes (5.9%) had a recurrence of the SRD after an earlier resolution. One of the 12 eyes had a spontaneous resolution of the SRD 6 months after PDT. The mean±standard deviation BCVA in logarithm of the minimum angle of resolution (logMAR) units significantly improved from 0.11±0.25 before to 0.07±0.23 at 1 month, 0.02±0.23 at 3 months, 0.01±0.23 at 6 months, 0.00±0.24 at 9 months, and -0.01±0.22 at 12 months (P<0.0001). The eyes with an SRD at 12 months were more likely to have an intermediate hyperfluorescence on ICGA (chi-square test, P<0.001) and poorer BCVA before the half-dose PDT (Student t test, P=0.04) than those without SRD at 12 months. None of the patients developed any systemic complications or experienced any severe visual reduction after the half-dose PDT. However, polypoidal lesion appeared in 1 eye 8 months after the PDT. CONCLUSIONS: Half-dose PDT is an effective and safe method to treat eyes with chronic CSC with an SRD. The CSC resolved and the BCVA improved significantly after PDT. Half-dose PDT was less effective for cases without intense hyperpermeability on ICGA and those with lower BCVA before the PDT.

Improvement in vision-related function with intravitreal aflibercept: data from phase 3 studies in wet age-related macular degeneration.

PURPOSE: To evaluate the effect of intravitreal aflibercept injection on visual function in wet age-related macular degeneration (AMD). DESIGN: Prospective, multicenter, double-masked, active-controlled, parallel-group, randomized phase 3 clinical studies (VEGF Trap-Eye: Investigation of Efficacy and Safety in Wet AMD [VIEW] 1 and 2 [clinicaltrials.gov identifiers, NCT00509795 and NCT00637377, respectively]). PARTICIPANTS: Patients (n=2419) with active, treatment-naïve, exudative AMD. This analysis included patients who received intravitreal aflibercept 2.0 mg every 8 weeks (2q8; n=607) or ranibizumab 0.5 mg every 4 weeks (0.5q4; n=595). INTERVENTION: Patients were randomized 1:1:1:1 to receive intravitreal aflibercept 2q8 (after 3 initial monthly doses), intravitreal aflibercept 2q4, intravitreal aflibercept 0.5q4, or ranibizumab 0.5q4 in the study eye. Patients in the intravitreal aflibercept 2q8 group received a sham injection alternating with active treatment. MAIN OUTCOME MEASURES: The 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) was administered at baseline and at weeks 12, 24, 36, and 52. The NEI VFQ-25 subscale scores were compared between intravitreal aflibercept 2q8 and ranibizumab 0.5q4 treatment arms, the approved dosing for each agent worldwide. Change in composite NEI VFQ-25 score was evaluated based on categorical change in visual acuity (worsened, unchanged, improved). RESULTS: Baseline NEI VFQ-25 scores were similar for both treatments in both studies. Mean change from baseline to 52 weeks was similar for ranibizumab 0.5q4 and intravitreal aflibercept 2q8 across all 12 subscales, with the greatest improvements noted for mental health and general vision (9.0-11.6 points, both treatments, both studies). Improvement of 4 points or more (both treatments, both studies) also was observed for subscales near vision, distance vision, role difficulties, and dependency. Mean change from baseline to 52 weeks in NEI VFQ-25 composite score (pooled data) stratified by clinical response showed meaningful improvement only in patients who gained 5 Early Treatment Diabetic Retinopathy letters or more (7.3 and 7.8 points for intravitreal aflibercept 2q8 and ranibizumab 0.5q4, respectively). CONCLUSIONS: Visual function outcomes were similar across all NEI VFQ-25 subscales over 52 weeks for intravitreal aflibercept 2q8 and ranibizumab 0.5q4, with clinically meaningful improvement recorded in 6 of 12 subscales.

RANDOMIZED CONTROLLED STUDY OF INTRAVITREAL BEVACIZUMAB 0.16 MG INJECTED ONE DAY BEFORE SURGERY FOR PROLIFERATIVE DIABETIC RETINOPATHY.

PURPOSE: To investigate the usefulness of 0.16 mg/0.05 mL intravitreal bevacizumab (IVB) injection 1 day before vitrectomy for proliferative diabetic retinopathy. METHODS: Sixty-two patients with proliferative diabetic retinopathy (66 eyes) with an indication for primary vitrectomy were randomized to IVB group (34 eyes) or sham control group (32 eyes). Intravitreal bevacizumab group received intravitreal injection of 0.16 mg/0.05 mL bevacizumab, and sham control group received sham injection 1 day before vitrectomy. Vitreous fluid was sampled before vitrectomy was started. RESULTS: Frequency of reoperation due to recurrent vitreous hemorrhage within 4 weeks after surgery was significantly lower (P = 0.033) in IVB group (3.1%, 1/32) than in sham control group (20.6%, 7/34). The number of intraoperative endodiathermy spots (0.63 ± 1.0 vs. 1.3 ± 1.4, P = 0.025) and frequency of postoperative recurrent vitreous hemorrhage (3.1%, 1/32 vs. 23.5%, 8/34, P = 0.017) were significantly lower in IVB group than in sham control group. Vitreous vascular endothelial growth factor concentrations were 1315.3 ± 1153.4 pg/mL in sham control group and 25.0 ± 13.6 pg/mL in IVB group (P < 0.0001). CONCLUSION: Intravitreal injection of 0.16 mg/0.05 mL bevacizumab 1 day before vitrectomy blocked vascular endothelial growth factor production in vitreous and significantly reduced the incidence of reoperation due to early postoperative recurrent vitreous hemorrhage.

Vitrectomy using 0.025% povidone-iodine in balanced salt solution plus for the treatment of postoperative endophthalmitis.

PURPOSE: To investigate the bactericidal effect of 0.025% povidone-iodine in Balanced Salt Solution PLUS (0.025% PI-BSS PLUS) and its use in vitrectomy for postoperative endophthalmitis. METHODS: First, an experimental laboratory model using Staphylococcus aureus was used to evaluate the bactericidal effect of PI-BSS PLUS. Next, in a case series of 4 eyes with postoperative endophthalmitis, vitrectomy using 0.025% PI-BSS PLUS as irrigation solution was conducted, followed by postoperative intravitreal and intravenous antibiotics. RESULTS: In in vitro study, PI at concentrations of 0.01% and above in BSS PLUS exhibited marked bactericidal effect after 15 seconds of exposure. Bactericidal effect of 0.025% PI-BSS PLUS was maintained at room temperature storage for 15 minutes but was attenuated after 30 minutes. Among 4 eyes that underwent vitrectomy using 0.025% PI-BSS PLUS, coagulase-negative Staphylococcus sp. was isolated in 1 eye at the beginning but not at completion of surgery. In all four eyes, endophthalmitis was resolved with no adverse events. Ocular toxicity was not observed. CONCLUSION: The 0.025% PI-BSS PLUS is bactericidal and nontoxic when used as irrigation solution in vitrectomy. In 4 cases of postoperative endophthalmitis, vitrectomy using 0.025% PI-BSS PLUS followed by postoperative antibiotics resolved endophthalmitis.

[Protection effect of astaxanthin against light-induced retinal damage in rat].

PURPOSE: To clarify the protective effect of astaxanthin (AST) against light-induced retinal damage in rats. METHODS: Albino rats were divided into three groups: a group treated orally with 1 mg/kg AST daily (group H), a group treated with 0.2 mg/kg AST (group L), and a control group (group C). Rats were administered AST in groups H and L and olive oil in group C followed by a 12-hour exposure to 3000-lux white light. After exposure for 7 days, the protective effect of AST was evaluated functionally by electroretinogram (ERG) and histologically by measuring outer nuclear layer (ONL) thickness and by counting rate of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) stained cells. RESULTS: After exposure to light, the b-wave amplitudes were significantly preserved in the AST groups compared to group C, Further the rate of the residual amplitude was higher in group H than in group L. The ONL thicknesses were significantly thicker in AST-treated rats compared to group C. The rates of TUNEL stained cells were significantly lower in the following order: group H, L and C. CONCLUSION: AST may have a protective effect against light-induced retinal damage in albino rats.

[Incidence of Postoperative Retinal Detachment after 25-gauge Vitrectomy for Macular Diseases].

PURPOSE: To examine the rate of postoperative retinal detachment following 25-gauge vitrectomy with extensive peripheral vitreous shaving in eyes with macular diseases. METHODS: A retrospective non-randomized study of 925 macular surgery cases was undertaken. All surgery was performed using 25-gauge vitrectomy and peripheral vitrectomy was done with scleral indentation. Epiretinal membrane (ERM) surgery (n = 523) and idiopathic macular hole (MH) surgery (n = 402) were performed between June 2005 and January 2014 by one surgeon (H. N.) and all cases were followed up for more than six months. We studied the rate of preexisting posterior vitreous detachment (PVD), endolaser treatment performed for retinal hole/tear and postoperative retinal detachment. RESULTS: Preexisting PVD was observed in 61.8% of eyes with ERM and in 10.7% of eyes with MH. The rate of endolaser treatment was 41.5% in ERM and 18.0% in MH cases, a statistically significant difference. Postoperative retinal detachment was seen in four of 925 eyes (0.43%) overall. CONCLUSION: Extensive peripheral vitrectomy using scleral indentation reduced the incidence of postoperative detachment occurring after 25-gauge macular surgery.

Morphologic features of focal choroidal excavation on spectral domain optical coherence tomography with simultaneous angiography.

PURPOSE: To reveal clinically relevant morphologic findings in patients with focal choroidal excavation (FCE) using enhanced depth imaging optical coherence tomography. METHODS: Thirty-one FCE lesions in 29 eyes of 26 patients (21 men, 23 eyes; 5 women, 6 eyes) were studies. In all 26 patients, color fundus photographs were obtained, and fluorescein angiography and indocyanine green angiography with simultaneous enhanced depth imaging optical coherence tomography were performed. Twenty-five eyes also underwent angiographic video recording. RESULTS: Focal choroidal excavation was detected in eyes with typical age-related macular degeneration, central serous chorioretinopathy, polypoidal choroidal vasculopathy, and idiopathic choroidal neovascularization, whereas in 8 eyes, FCE was considered to be idiopathic. Morphologically, FCE lesions were classified into 3 types: cone-shaped, bowl-shaped, and mixed. The cone-shaped type was detected in 17 lesions, bowl-shaped in 8, and mixed in 6, on optical coherence tomography findings. All bowl-shaped and mixed types had retinal pigment epithelial irregularities within the FCE lesion. The cone-shaped type was not observed in eyes with typical age-related macular degeneration. CONCLUSIONS: Morphologically, FCE lesions were classified into cone-shaped, bowl-shaped, and mixed types, based on optical coherence tomography findings. Focal choroidal excavation formation may be associated in part with chorioretinal diseases such as age-related macular degeneration and central serous chorioretinopathy, whereas some eyes are considered to have idiopathic FCE.

Quantification of metamorphopsia in chronic central serous chorioretinopathy after half-dose verteporfin photodynamic therapy.

PURPOSE: To determine the degree of metamorphopsia before and 1 year after half-dose verteporfin photodynamic therapy in eyes with chronic central serous chorioretinopathy. METHODS: This was a retrospective, noncomparative, interventional case series. Forty-five eyes of 45 consecutive patients with chronic central serous chorioretinopathy were evaluated. The degree of metamorphopsia was measured with M-CHARTS before and at 1, 3, 6, 9, and 12 months after half-dose verteporfin photodynamic therapy. The best-corrected visual acuity was also measured. RESULTS: Forty of the 45 eyes had a complete resolution of the serous retinal detachment at 1 month, 1 eye at 3 months, and 3 eyes at 6 months. The serous retinal detachment in one eye persisted throughout the follow-up period. The mean horizontal metamorphopsia score improved significantly from 0.61 ± 0.52° at baseline to 0.49 ± 0.56° at 12 months (P = 0.04). The vertical metamorphopsia score improved significantly from 0.52 ± 0.53° at baseline to 0.33 ± 0.46° at 12 months (P = 0.005). CONCLUSION: Half-dose verteporfin photodynamic therapy for chronic central serous chorioretinopathy results in significant improvements of metamorphopsia at 1 year, especially in eyes with good best-corrected visual acuity at the baseline. Half-dose verteporfin photodynamic therapy can be a therapeutic option for patients with good visual acuity who complain of metamorphopsia.

Choroidal thickness measurement by enhanced depth imaging and swept-source optical coherence tomography in central serous chorioretinopathy.

BACKGROUND: We evaluated subfoveal choroidal thickness measured with two different forms of optical coherence tomography (OCT), enhanced-depth imaging (EDI) and swept-source (SS) OCT, in central serous chorioretinopathy (CSC). METHODS: Fifty-six eyes of 48 patients diagnosed with acute or chronic CSC, were studied prospectively. Subfoveal choroidal thickness was measured as the distance between the outer border of the retinal pigment epithelium-Bruch's membrane complex, and the chorioscleral border under the fovea. Subfoveal choroidal thickness was measured using EDI-OCT and SS-OCT. We also measured serous retinal detachment (SRD) only with SS-OCT. The Pearson correlation coefficient was used to assess the correlation between subfoveal choroidal thickness values determined by the two different OCT modalities. RESULTS: The mean patient age was 52 ± 13 years (range, 32-82 years). Among the 56 eyes, 21 had acute CSC and 35 had chronic CSC. Subfoveal choroidal thickness measured with EDI-OCT was 336.6 ± 91.6 µm in acute and 388.0 ± 103.4 µm in chronic CSC. With SS-OCT, the thickness in acute CSC was 332.0 ± 96.7 µm and that in chronic CSC was 392.6 ± 101.3 µm. Acute CSC (p <0.001, correlation coefficient; r = 0.99) and chronic CSC (p <0.001, correlation coefficient; r = 0.97) values obtained with the two different OCT modalities correlated significantly. Among the 56 eyes, 43 (19 eyes with acute and 24 with chronic CSC) were evaluable for SRD height by SS-OCT. The mean SRD height was 128.9 ± 83.6 µm in acute cases and 96.3 ± 62.0 µm in chronic cases. CONCLUSIONS: Subfoveal choroidal thickness obtained with two different OCT modalities correlated significantly.

Associations of complement factor B and complement component 2 genotypes with subtypes of polypoidal choroidal vasculopathy.

BACKGROUND: We previously reported on subtypes of polypoidal choroidal vasculopathy (PCV), and categorized PCV as polypoidal choroidal neovascularization (CNV) and typical PCV. The aim of this study was to clarify whether complement component 2 (C2) and complement factor B (CFB) genotypes are associated with subtypes of polypoidal choroidal vasculopathy, such as polypoidal CNV and typical PCV. METHODS: First, we categorized 677 patients into typical age-related macular degeneration (tAMD; 250 patients), PCV (376) and retinal angiomatous proliferation (RAP; 51). Second, we categorized 282 patients with PCV as having polypoidal CNV (84 patients) or typical PCV (198) based on indocyanine green angiographic findings. In total, 274 subjects without AMD, such as PCV and CNV, served as controls. A SNP (rs547154) in the C2 gene and three SNPs (rs541862, rs2072633, rs4151667) in the CFB gene were genotyped, and case-control studies were performed in subjects with these PCV subtypes. RESULTS: In tAMD, no SNPs were associated with allele distributions. In PCV, rs547154 and rs2072633 were associated with allele distributions. RAP was only associated with rs2072633. After logistic regression analysis with adjustment for confounding factors, tAMD, PCV and RAP were found to be associated with rs2072633.As to PCV subtypes, there were significant differences in the distributions of rs547154, rs541862 and rs2072633 in the case-control studies for polypoidal CNV, but not between the typical PCV and control groups. Logistic regression analysis with adjustment for confounding factors showed the distributions of rs547154, rs541862 and rs2072633 to differ significantly between the controls and polypoidal CNV cases and that these SNPs were protective. The A/A genotype of rs2072633 was significantly more common in the polypoidal CNV than in the typical PCV group (p = 0.03), even with adjustment for polyp number and greatest linear dimension. CONCLUSIONS: PCV might be genetically divisible into polypoidal CNV and typical PCV. The C2 and CFB gene variants were shown to be associated with polypoidal CNV. Typical PCV was not associated with variants in these genes.

[Japan phase 3 study of pegaptanib sodium in patients with diabetic macular edema].

PURPOSE: To evaluate the efficacy and safety of intravitreal injections of pegaptanib sodium in subjects with diabetic macular edema (DME). METHODS: There were 243 subjects with DME who were randomized to receive, every 6 weeks, either an intravitreal injection of pegaptanib sodium or a sham injection. The study was double-masked for the first 24 weeks, and then an open label phase continued to week 54. The primary efficacy endpoint was evaluated at week 24, and safety was assessed throughout the 54 weeks. RESULTS AND CONCLUSION: The proportion of subjects who experienced more than 10 letters improvement of visual acuity in ETDRS chart from baseline to week 24 was statistically significantly greater (p-value = 0.0003) in the pegaptanib sodium group, 20.3%, than in the sham group, 5.0%. The incidence of treatment-related adverse events was similar between the treatment groups (pegaptanib sodium group: 10.6%, sham group: 10.0%). The reported adverse events were mainly mild or moderate ophthalmic events and related to the injection procedure. During open-label phase up to 54 weeks, no new safety concerns were identified compared with the double-masked phase. However, in light of the issue concerning proper maintenance of masking of the study treatments, the study was not considered as a well-controlled, double-masked study.