INCIDENCE AND CHARACTERISTICS OF NEOVASCULAR AGE-RELATED MACULAR WITH OVER A 12-MONTH REMISSION AFTER THREE MONTHLY AFLIBERCEPT ADMINISTRATION: 60 Months Results of a Pro Re Nata Regimen.

PURPOSE: To investigate the characteristics of patients with over a 12-month remission after 3 monthly intravitreal aflibercept injections followed by a pro re nata regimen for exudative age-related macular degeneration (AMD). METHODS: One hundred forty-four eyes with exudative AMD were included. All patients received 3 monthly intravitreal aflibercept injections as a loading dose, followed by an as-needed regimen for 60 months. Patients were classified into the remission and recurrence groups depending on the presence or absence of a 12-month remission. ARMS2 A69S and CFH I62V were genotyped in all cases. RESULTS: During the study, 82 eyes (56.9%) showed 12 months or more remission at least once. The cumulative incidence rate of a 12-month remission showed a plateau pattern and converged to 60% (y = -166.26x-2.172 + 0.6, R2 = 0.8168). Patients in the remission group were younger than those in the recurrence group (P < 0.001) and had less risk allele frequency of the ARMS2 gene than the recurrence group (P < 0.001). The longer the remission interval was prolonged, the better visual acuity was achieved at the 60-month visit (P < 0.001). CONCLUSION: Fifty-seven percent of patients showed a 12-month remission or more at least once during a 60-month follow-up, suggesting that patients with no reactivation can prolong the treatment interval.

Comparison of one-year outcomes between as-needed brolucizumab and aflibercept for polypoidal choroidal vasculopathy.

PURPOSE: To compare the one-year visual and anatomic outcomes of an as-needed regimen of brolucizumab and aflibercept for polypoidal choroidal vasculopathy (PCV). STUDY DESIGN: A retrospective comparative study. METHODS: A retrospective medical chart review was performed for consecutive 56 eyes from 56 patients with PCV initially treated with thee monthly intravitreal aflibercept (n = 33, 2.0 mg/0.05 ml) or brolucizumab (n = 23, 6.0 mg/0.05 ml) followed by as-needed administration, followed up for at least 12 months. All patients were followed up monthly, and fluorescein and indocyanine green angiography (ICGA) were performed at baseline, 3-month, and 12-month visits. RESULTS: At the 12-month visit, best-corrected visual acuity significantly improved from 0.30 ± 0.31 to 0.21 ± 0.29 (p = 0.042) in the brolucizumab-treated group and from 0.24 ± 0.25 to 0.14 ± 0.25 (p = 7.7×10-3) in the aflibercept-treated group, suggesting comparable visual improvement in both groups. Central retinal thickness and subfoveal choroidal thickness decreased by 38.4% and 14.2%, respectively, in the brolucizumab-treated group and by 34.8% and 13.9%, respectively, in the aflibercept-treated group at the 12-month visit. The mean number of additional injections was significantly higher in the aflibercept-treated group (2.9 ± 2.7) than in the brolucizumab-treated group (1.3 ± 1.2, p = 0.045). The complete resolution of polypoidal lesions on ICGA was higher in the brolucizumab-treated group than in the aflibercept-treated group (3-month visit: 56.5% vs 30.3%, 12-month visit: 56.5% vs 30.3%). CONCLUSIONS: In treatment-naïve eyes with PCV, the as-needed administration regimen of brolucizumab was comparable to aflibercept in terms of visual and anatomical outcomes, with fewer additional injections during the 12-month follow-up.

A Treat-and-Extend Regimen of Intravitreal Brolucizumab for Exudative Age-Related Macular Degeneration Refractory to Aflibercept: A 12-Month Result.

We aimed to investigate whether a treat-and-extend regimen of intravitreal brolucizumab (6.0 mg/0.05 mL) is effective for eyes with exudative age-related macular degeneration (AMD) refractory to aflibercept for 12 months. Sixty eyes from 56 patients receiving brolucizumab for exudative AMD refractory to aflibercept were included. Patients received a mean of 30.1 aflibercept administrations for a mean 67.9-month follow-up. All patients exhibited exudation on optical coherence tomography (OCT) despite regular 4-8 weeks of aflibercept administration. Visit 1 was scheduled at the same interval from the last aflibercept injection to the baseline. The treatment interval was extended or shortened by 1-2 weeks depending on the presence or absence of exudation on OCT. After switching to brolucizumab, the follow-up interval significantly extended at 12 months (before switching: 7.6 ± 3.8 weeks vs. at 12 months: 12.1 ± 6.2 weeks, p = 1.3 × 10-7). Forty-three percent of the eyes achieved a dry macula at 12 months after switching. However, the best-corrected visual acuity did not improve at any visit. Morphologically, the central retinal thickness and subfoveal choroidal thickness significantly decreased from baseline at 12 months (p = 3.6 × 10-3 and 1.0 × 10-3, respectively). Switching to brolucizumab can be considered to extend the treatment interval in eyes with exudative AMD refractory to aflibercept.

Repeated Measurements Are Necessary for Evaluating Accurate Diurnal Rhythm Using a Self-Intraocular Pressure Measurement Device.

PURPOSE: To investigate how many tests need to be performed to adequately assess intraocular pressure (IOP) diurnal change using a self-measuring rebound tonometer among glaucoma patients. SUBJECTS AND METHODS: Adult patients with primary open-angle glaucoma were included. IOP was measured in the morning (6 AM to 9 AM), afternoon (12 PM to 3 PM), and at night (6 PM to 9 PM) for seven consecutive days. Twenty-four (7 males and 17 females, mean age 59.5 ± 11.0 years) patients who successfully measured IOP at least three times per day during the correct time periods for four days were subjected to analysis. RESULTS: The IOP rhythm was significantly greater on the first day of measurement (6.6 ± 3.6 mmHg) than that averaged during subsequent days (4.4 ± 2.2 mmHg). The time of the highest and lowest IOP measurements on the first day of IOP measurement and during the entire measurement period coincided in 72.9% and 64.6% of cases, respectively. The concordance rate of the highest IOP time between the whole measurement period and each measurement day was less than 60%. CONCLUSION: The diurnal IOP rhythm measured by the patients themselves was not consistent, and multiple days of measurements may be necessary to correctly assess diurnal IOP rhythm.

Mid-Term Results of Ab Interno Trabeculectomy among Japanese Glaucoma Patients.

BACKGROUND: The evaluation of ab interno trabeculectomy, referred to as trabectome®, among Japanese patients is insufficient. SUBJECTS AND METHODS: Japanese patients who underwent trabectome® at the University of Yamanashi Hospital were included. The investigated parameters were intraocular pressure (IOP), best corrected visual acuity, glaucoma medications, visual field, and corneal endothelial cell density. The success rate and its associated factors were investigated. RESULTS: A total of 250 eyes from 197 patients were enrolled. The trabectome® significantly reduced IOP and glaucoma medications up to 48 months. Concomitant cataract extraction enhanced the reduction in IOP and glaucoma medications up to 42 months. At 36 months postoperatively, 40.8% satisfied IOP of the same or less than 18 mmHg or more than a 20% IOP reduction with the same or less use of glaucoma medications as preoperatively. Preoperative IOP and combined cataract extraction were significantly associated with the success rate. The trabectome® alone did not show a significant reduction in corneal endothelial cells. Eyes with postoperative transient IOP elevation and removal of anterior chamber hemorrhage were 11.2% and 1.2%, respectively. Twenty-four eyes (9.6%) underwent additional glaucoma surgeries. CONCLUSIONS: The trabectome® could be considered an effective and safe surgery. Compared to trabectome® alone, combined cataract surgery was superior in lowering IOP and reducing glaucoma medications.

DISTINCT CHARACTERISTICS OF SIMPLE VERSUS COMPLEX CENTRAL SEROUS CHORIORETINOPATHY.

PURPOSE: To compare the clinical and genetic characteristics of simple and complex central serous chorioretinopathy using central serous chorioretinopathy international group criteria. METHODS: Patients with idiopathic central serous chorioretinopathy were included. Depending on the presence or absence of retinal pigment alterations greater than 2-disc areas in either eye, patients were classified into complex or simple types. Demographic factors and clinical findings were compared between groups. CFH variants, including rs800292 and rs1329428, were genotyped using TaqMan technology. RESULTS: A total of 319 consecutive patients were evaluated at the initial presentation. Of them, 53 (16.6%) had the complex type. The complex type was exclusively seen in men (100% vs. 79.0%, P = 2.0 × 10 -4 ) and demonstrated a significantly higher proportion of bilateral involvement (75.5% vs. 17.7%, P = 6.2 × 10 -18 ) and descending tract(s) (83.0% vs. 0%, P = 1.2 × 10 -57 ) than the simple type. Increased choroidal thickness (425 ± 131 vs. 382 ± 110, P = 0.02) and decreased central retinal thickness (274 ± 151 vs. 337 ± 136, P = 2.9 × 10 -4 ) were observed for the complex versus simple type. The risk allele frequencies of both variants were significantly higher in the complex versus simple type (rs800292: 61.3% vs. 48.7%, P = 0.018; rs1329428: 65.1% vs. 54.3%, P = 0.04). CONCLUSION: In this new classification system, the complex type has distinct genetic and clinical characteristics compared with the simple type.

Characteristics of intermediate age-related macular degeneration with hyperreflective foci.

Hyperreflective foci (HRF) are the findings observed in optical coherence tomography (OCT) in several retinal diseases and are believed to be associated with the increased risk of atrophy in eyes with age-related macular degeneration (AMD). In this study, we investigated the clinical and genetic characteristics of intermediate AMD with HRF. We reviewed the medical charts for 155 patients with intermediate AMD, in whom macular neovascularization (MNV) was observed in the contralateral eye. The presence or absence of an HRF was evaluated using a spectral-domain OCT volume scan spanning the macular region. Patients were followed longitudinally for at least 12 months, and the maximum follow-up period was 60 months. Genotyping of ARMS2 A69S and CFH I62V was performed in all participants. Of the 155 patients (mean age: 77.8 ± 7.6 years, male/female: 103/52), HRF was observed in 53 eyes (34.2%) and was significantly associated with type-3 MNV (p = 1.0 × 10-5) in the contralateral eye, pseudodrusen (p = 5.0 × 10-4), thinner subfoveal choroidal thickness (p = 0.013), and risk of ARMS2 A69S (p = 0.023). During follow-up (40.8 ± 17.5), 38 eyes (24.5%) developed advanced AMD. The mean time to the onset of advanced AMD was 29.8 ± 12.9 months in eyes with intermediate AMD. HRF was associated with MNV (p = 1.0 × 10-3), but not with atrophy.

Distinct characteristics of central serous chorioretinopathy according to gender.

To investigate the differences in clinical and genetic characteristics between males and females with central serous chorioretinopathy (CSC). Consecutive 302 patients (mean age; 56.3 ± 11.7, male/female: 249/53) with CSC were evaluated on the initial presentation. All CSC patients underwent fluorescein angiography and indocyanine green angiography (FA/ICGA), swept-source or spectral-domain optical coherence tomography (OCT), and fundus autofluorescence (FAF) to confirm a diagnosis. All patients were genotyped for rs800292 and rs1329428 variants of CFH using TaqMan technology. On the initial presentation, female patients were significantly older (p = 2.1 × 10-4, female 61.6 ± 12.4 vs male 55.1 ± 11.3) and had thinner subfoveal choroidal thickness (p = 3.8 × 10-5) and higher central retinal thickness (p = 3.0 × 10-3) compared to males. A descending tract was more frequently seen in males than in females (p = 8.0 × 10-4, 18.1% vs 0%). Other clinical characteristics were comparable between the sexes. The risk allele frequency of both variants including CFH rs800292 and CFH rs1329428 was comparable between males and females (CFH rs800292 A allele male 51.2% vs female 47.2%, CFH rs1329428 T allele male 56.2% vs 52.8%). On the initial presentation, age, subfoveal choroidal thickness and central retinal thickness differ between males and females in eyes with CSC. A descending tract may be a strong male finding in CSC.

The combination therapy of subtenon triamcinolone acetonide injection and intravitreal brolucizumab for brolucizumab-related intraocular inflammation.

RATIONALE: Brolucizumab is a novel anti-vascular endothelial growth factor agent with clinical trials demonstrating excellent efficacy for neovascular age-related macular degeneration (AMD) in both visual and anatomic outcomes. However, there is concern of intraocular inflammation (IOI), and we propose concurrent subtenon triamcinolone acetonide (STTA) to prevent IOI. PATIENT CONCERN: A 73-year-old man was treated with aflibercept for neovascular AMD in his right eye. Despite 11 months of monthly intravitreal aflibercept injections, optical coherence tomography demonstrated persistent exudation. Ten days following his second brolucizumab injection, the patient presented with decreased vision due to vitritis in his right eye. DIAGNOSIS: Brolucizumab-related IOI in neovascular AMD refractory to aflibercept. INTERVENTIONS: A combination therapy involving of intravitreal brolucizumab and STTA. OUTCOMES: The anti-vascular endothelial growth factor inhibitor was changed back to aflibercept; however, exudation persisted. Therefore, a combination therapy involving STTA (5 mg/0.5 mL) and intravitreal injection of brolucizumab (6.0 mg/0.05 mL) was performed to treat the exudation and as prophylaxis to recurrent IOI. Combination therapy achieved no recurrent IOI and resolution of exudation with 8-week treatment intervals. LESSONS: This case might indicate that STTA is not only an optimal treatment option for brolucizumab-related IOI but also a preventive agent for this condition.

Comparison of Outcomes between 3 Monthly Brolucizumab and Aflibercept Injections for Polypoidal Choroidal Vasculopathy.

We compared the short-term outcomes between 3-monthly aflibercept and brolucizumab injections for treatment-naïve polypoidal choroidal vasculopathy (PCV). A total of 52 eyes were included. Patients received 3 monthly intravitreal aflibercept (n = 38) or intravitreal brolucizumab (n = 14). Indocyanine green angiography (ICGA) was performed at baseline and at the 3-month visit. Selection of anti-VEGF agents depended on time. In the brolucizumab-treated group, best-corrected visual acuity (BCVA) improved from 0.27 ± 0.34 (log MAR unit) at baseline to 0.20 ± 0.24 at 3-month visit, which is comparable with the aflibercept-treated group (p = 0.87), after adjustment of confounding factors. Central retinal thickness significantly decreased by 43%-44% in both groups. Subfoveal choroidal thickness also significantly decreased by 20.5% during this interval in the brolucizumab-treated group, which was greater than the aflibercept-treated group. The complete resolution rate of polypoidal lesions on ICGA was significantly higher (p = 0.043) in the brolucizumab-treated group (78.6%) than in the aflibercept-treated group (42.1%). Intraocular inflammation was observed in 14.3% (2/14) in the brolucizumab-treated group only. In short-term follow-up, intravitreal injection of 3-monthly brolucizumab was comparable with aflibercept in terms of BCVA and morphological improvement along with higher resolution of polypoidal lesion(s) on ICGA.

Long-term prognosis of polypoidal choroidal vasculopathy with a 5-year remission after an initial combination therapy.

PURPOSE: To investigate the visual prognosis of patients with polypoidal choroidal vasculopathy (PCV) with a 5-year remission after an initial combination therapy involving photodynamic therapy (PDT) and intravitreal ranibizumab (IVR) or aflibercept injection (IVA). METHODS: Medical records of 69 consecutive patients with PCV treated with PDT with IVR/IVA were retrospectively reviewed, and 17 eyes were identified with a 5-year remission after the initial combination therapy. The eyes that did not require additional treatment during the 1st-5th year were assigned to the remission group and the eyes requiring additional treatment during the 1st-5th year were assigned to the recurrence group. RESULTS: During the 7-year follow-up, the mean logarithm of the minimal angle resolution best-corrected visual acuity (logMAR BCVA) significantly improved from 0.39±0.27 to 0.17±0.38 (p=2.9 × 10-4) in the remission group, whereas the mean logMAR BCVA was maintained throughout the follow-up period (0.58±0.27 to 0.60±0.48) in the recurrence group. In the remission group, only two (11.8%) of the 17 eyes experienced recurrence during the 5th-7th year. Comparison of baseline characteristics between the two groups revealed that a higher proportion of female (p=0.012), better baseline BCVA (p=3.1 × 10-3), and lower risk allele frequency in ARMS2 A69S (p=0.029) were observed in the remission group. CONCLUSIONS: The combination therapy showed a favourable outcome for PCV over a 7-year follow-up, especially in the eyes without recurrence during the 1st-5th year. Physicians should be careful of recurrent exudation in the eyes without recurrence during the 1st-5th years, although the recurrence rate was low.

Myelin oligodendrocyte glycoprotein antibody-associated optic neuritis in a COVID-19 patient: A case report.

RATIONALE: Coronavirus disease 2019 (COVID-19) has spread worldwide. It involves multiple organs of infected individuals and encompasses diverse clinical manifestations. We report a case of acute optic neuritis (ON) associated with myelin oligodendrocyte glycoprotein (MOG) antibody possibly induced by COVID-19. PATIENT CONCERNS: A 47-year-old man presented to our clinic with left eye pain and vision loss. Magnetic resonance imaging of the orbit revealed the bilateral high intensity of the optic nerve sheaths. He tested positive for COVID-19 by polymerase chain reaction (PCR) testing on the day of admission but he had no signs of respiratory illness. Laboratory testing revealed that MOG immunoglobulin G (MOG IgG) was positive, but other antibodies including aquaporin-4 were negative. DIAGNOSIS: The patient was diagnosed with MOG antibody-positive acute ON possibly induced by COVID-19. INTERVENTIONS: Steroid pulse therapy consisting of methylprednisolone 1 g/day for a total of 3 days, followed by an oral prednisolone taper was performed. OUTCOMES: His left eye pain was immediately relieved, and his decimal vision improved from 0.03 to 0.1 on the day of discharge. Outpatient follow-up 2 weeks later revealed left a decimal vision of 1.2, and a complete resolution of the left eye pain. LESSONS: Our case indicated that COVID-19 might trigger an autoimmune response that leads to MOG antibody-associated ON, similar to other pathogens that were reported in the past. The treatment response to steroid pulse therapy was preferable following a typical course of MOG antibody-positive ON.

Five-Year Outcome of Aflibercept Monotherapy for Exudative Age-Related Macular Degeneration with Good Baseline Visual Acuity.

We investigated the long-term visual and anatomical outcomes of aflibercept monotherapy for exudative age-related macular degeneration (AMD) with good baseline best-corrected visual acuity (BCVA). A medical chart review was performed for 40 consecutive patients with baseline decimal BCVA ≥ 0.6 secondary to exudative AMD. Three monthly injections were administrated, and thereafter additional injection was performed if needed over 5 years. In total, 13 eyes with neovascular AMD (nAMD) and 27 eyes with polypoidal choroidal vasculopathy (PCV) were enrolled. In both groups, the mean BCVA significantly improved at the 12-month visit (p < 0.05). However, the significant improvement in BCVA disappeared at the 24-month visit, and the final mean BCVA was equivalent to that at baseline (p = 0.17 in the nAMD group and p = 0.15 in the PCV group). The median number of injections required after the loading dose was 15.0 during the 5-year follow-up (nAMD:15.0 vs. PCV:15). During the study period, 37 (92.5%) eyes required retreatment(s). Cox regression analysis demonstrated that the protective allele of ARMS2 A69S was associated with a retreatment-free period from the initial injection (p = 0.041, repeated forward selection method). As-needed aflibercept monotherapy is a preferable treatment option for exudative AMD with good initial visual acuity regardless of nAMD or PCV during the 5-year study period.

Medical Costs of and Changes in Glaucoma Treatment among Patients Newly Starting Glaucoma Care.

Purpose: To use a medical claim database to investigate medical costs and treatment patterns among patients newly starting glaucoma care.Subjects and methods: Subjects registered in the Japan Medical Database Center (JMDC) from January 2005 to March 2016 who were newly diagnosed with glaucoma, started glaucoma treatment, and had treatment records covering more than five years were included in the analysis. All direct medical costs were collected for a period of up to ten years. Factors affecting medical costs were analyzed. Changes in hypotensive eyedrops and choices related to glaucoma surgery were also analyzed.Results: Out of approximately 1.42 million subjects, 2,393 satisfied the inclusion and exclusion criteria. The average total medical cost incurred per patient over a period of ten years was US$9,030, including US$1,214 during the initial year. The proportion of the total cost represented by the cost of hypotensive eyedrops increased from 5.2% to 10.6% over the ten-year period. Medical costs were higher in patients younger than ten years old than in patients of all other age groups. The number of ocular hypotensive eyedrops increased from 0.9 to 1.5 over the ten-year period. Medical costs were higher for subjects with secondary glaucoma than for other subjects. Sixty-three patients underwent trabeculotomy or trabeculectomy, and trabeculectomy was the preferred choice in later years.Conclusions: The total direct medical cost associated with glaucoma was US$9,030 for the first ten years. Drug costs gradually increased with treatment duration and patient age and varied by glaucoma type.

Association between Polygenic Risk Score and One-Year Outcomes Following As-Needed Aflibercept Therapy for Exudative Age-Related Macular Degeneration.

We investigated whether polygenic risk score (PRS) was associated with one-year outcome of as-needed aflibercept therapy for exudative age-related macular degeneration (AMD), including AMD (n = 129) and polypoidal choroidal vasculopathy (n = 132). A total of 261 patients were treated with as-needed intravitreal aflibercept injection (IAI) after three monthly IAIs and the completion of a one-year follow-up. One hundred and seventy-two healthy volunteers served as controls. Genotyping of ARMS2 A69S (rs10490924), CFH I62V (rs800292), SKIV2L-C2-CFB (rs429608), C3 (rs2241394), ADAMTS-9 (rs6795735) and CETP (rs3764261) was performed for all participants. A total of 63 PRSs were quantified. There was a positive association between the PRS involving ARMS2, CFH, C3, and ADAMTS-9 and best-corrected visual acuity at twelve months (p = 0.046, multiple regression analysis). When comparing PRSs of patients requiring retreatment and of patients without retreatment, 35 PRSs were significantly greater in patients requiring retreatment than in patients without requiring retreatment, with the PRS involving ARMS2 and CFH being most significantly associated (p = 1.6 × 10-4). The number of additional injections was significantly associated with 40 PRSs and the PRS involving ARMS2 and CFH showed a most significant p-value (p = 2.42 × 10-6). Constructing a PRS using a combination with high-risk variants might be informative for predicting the response to IAI for exudative AMD.

Response to photodynamic therapy combined with intravitreal aflibercept for polypoidal choroidal vasculopathy depending on fellow-eye condition:2-year results.

We investigated whether response to photodynamic therapy (PDT) with intravitreal aflibercept injection (IAI) for polypoidal choroidal vasculopathy (PCV) differs depending on fellow eye condition. A retrospective review was conducted for consecutive 60 eyes with PCV treated with PDT combined with IAI as well as 2-years of follow-up data. Fellow eyes were divided into 4 groups; Group 0: no drusen, Group 1; pachydrusen, Group 2; soft drusen, Group 3: PCV/fibrovascular scarring. Best-corrected visual acuity improved at 24-months irrespective of groups and there were no significant differences in visual improvement among treated eyes among the 4 groups. Within 2-years, 35 (58.3%) required the retreatment. The need for retreatment including additional injection and the combination therapy was significantly less in Group 1(12.5%) compared to the others (P = 0.0038) and mean number of additional IAI was also less in Group 1 compared to the others (P = 0.017). The retreatment-free period from the initial combination therapy was longest in Group 1 (23.6±1.1 months) (P = 0.0055, Group 0: 19.1±6.9, Group 2: 12.8±7.9, Group 3: 11.5±9.9). The need for retreatment was significantly different according to fellow-eye condition. Among PCV patients, pachydrusen in fellow eyes appear to be a predictive characteristic for a decreased treatment burden at 2 years.

Title: Pachydrusen in Fellow Eyes Predict Response to Aflibercept Monotherapy in Patients with Polypoidal Choroidal Vasculopathy.

We investigated whether responses to as-needed intravitreal aflibercept injections (IAIs) for polypoidal choroidal vasculopathy (PCV) differed among patients based upon drusen characteristics in fellow eyes. 110 eyes from 110 patients with PCV received 3 monthly IAI and thereafter Pro re nata (PRN) IAI over 12 months. Patients were classified into 4 groups depending on fellow eye findings. Group 1 (n = 16): pachydrusen; Group 2 (n = 45): no drusen; Group 3 (n = 35): soft drusen; Group4 (n = 14) PCV/scarring. Best-corrected visual acuity improved at 12 months in all groups, but not significantly in Group 1 and Group 4; however, visual improvement was similar among the groups after adjusting baseline confounders. Group 1 had a significantly lower percentage of eyes needing retreatment (all p < 0.001; Group 1: 16.7%; Group 2: 50.8%; Group 3: 80%; Group 4: 85.7%). The mean number of retreatments was least in Group 1 among the groups (all p-value < 0.003; Group 1: 0.50 ± 1.32; Group 2: 1.73 ± 2.08; Group 3:2.71 ± 1.99; Group 3: 2.71 ± 2.16). Patients with pachydrusen in fellow eyes were less likely to require additional IAI following the loading dose and may be ideal candidates for aflibercept monotherapy in their first year.

Association of CRP levels with ARMS2 and CFH variants in age-related macular degeneration.

PURPOSE: To investigate whether plasma high sensitivity C-reactive protein (hs-CRP) level is associated with exudative age-related macular degeneration (AMD) as well as variants of ARMS2 A69S and CFH I62V in patients with exudative AMD. METHODS: A case-control study was done comparing CRP among patients with exudative AMD including those with polypoidal choroidal vasculopathy, typical AMD and retinal angiomatous proliferation, and CRP were also compared between cases and controls. Plasma CRP was measured from peripheral blood using latex nepherometry for all participants. Genotyping of ARMS2 A69S and CFH I62V was performed for all patients with exudative AMD using TaqMan technology. RESULTS: Among 125 patients with exudative AMD, including 31 with typical neovascular AMD, 73 with PCV and 21 with RAP lesions and 150 controls, CRP levels were higher in exudative AMD than in controls. (P = 2.7 × 10-5) There was not a significant difference in hs-CRP levels among AMD subtypes. Neither variants of ARMS2 nor CFH was associated with hs-CRP level in patients with exudative AMD. A multiple regression analysis revealed that gender male, presence of exudative AMD and presence of cardiovascular diseases were associated with increased plasma hs-CRP. CONCLUSIONS: Plasma hs-CRP was elevated independent of variants of ARMS2 A69S and CFH I62V in patients with exudative AMD.

Genetic factors associated with response to as-needed aflibercept therapy for typical neovascular age-related macular degeneration and polypoidal choroidal vasculopathy.

In the present study, we investigated the association between susceptible genetic variants to age-related macular degeneration (AMD) and response to as-needed intravitreal aflibercept injection (IAI) therapy for exudative AMD including both typical neovascular AMD and polypoidal choroidal vasculopathy (PCV) over 12-months. A total of 234 patients with exudative AMD were initially treated with 3 monthly IAI and thereafter as-needed IAI over 12 months. Seven variants of 6 genes including ARMS2 A69S (rs10490924), CFH (I62V:rs800292 and rs1329428), C2-CFB-SKIV2L(rs429608), C3 (rs2241394), CETP (rs3764261) and ADAMTS-9 (rs6795735) were genotyped for all participants using TaqMan technology. After adjusting for age, gender, baseline BCVA and AMD subtype, A (protective) allele of C2-CFB-SKIV2L rs429608 was associated with visual improvement at 12-month (P = 0.003). Retreatment was associated with T(risk) allele of ARMS2 A69S (P = 2.0 × 10-4; hazard ratio: 2.18:95%CI: 1.47-3.24) and C(risk) allele of CFH rs1329428 (P = 2.0 × 10-3; hazard ratio: 1.74:95%CI: 1.16-2.59) after adjusting for the baseline confounders. The need for additional injections was also associated with T allele of ARMS2 A69S (P = 1.0 × 10-5) and C allele of CFH rs1329428 (P = 3.0 × 10-3) after adjusting for the baseline confounders. The variants of ARMS2 and CFH are informative for both physicians and patients to predict recurrence and to quantify the need for additional injections.

Correction: Five-year outcomes of photodynamic therapy combined with intravitreal injection of ranibizumab or aflibercept for polypoidal choroidal vasculopathy.

[This corrects the article DOI: 10.1371/journal.pone.0229231.].