Dexamethasone Intravitreal Implant for Early Treatment and Retreatment of Macular Edema Related to Branch Retinal Vein Occlusion: The Multicenter COBALT Study.

PURPOSE: To evaluate the effect of dexamethasone intravitreal implant for macular edema (ME) following branch retinal vein occlusion (BRVO) in Korean patients. METHODS: We performed a prospective, open-label, multicenter study of 71 patients with ME for < 3 months. Retreatment was allowed ≥4 months from the last injection. RESULTS: At 6 and 12 months, mean ± SD best-corrected visual acuity (BCVA) improvement was 18.6 ± 12.9 and 15.3 ± 15.0 letters, respectively. Approximately 70% of maximum treatment response was observed after 1 week. Over the 12-month period, 32 and 49% of patients received 1 and 3 injections, respectively, with a mean ± SD interval of 20.0 ± 5.0 weeks. Patients who required 3 injections had higher central retinal thickness (CRT) and larger macular nonperfusion at baseline compared to those requiring only 1 injection. Adverse events included increased intraocular pressure (35%) and newly diagnosed cataract (16%). CONCLUSIONS: Intravitreal dexamethasone treatment with an interval of ≥4 months provides rapid and significantly better improvement in BCVA and CRT in patients with BRVO-associated ME.

ANGIOPOIETIN-LIKE 4 CORRELATES WITH RESPONSE TO INTRAVITREAL RANIBIZUMAB INJECTIONS IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To investigate whether the aqueous angiopoietin-like 4 (ANGPTL4) level correlates with clinical features in neovascular age-related macular degeneration (AMD). METHODS: The control and study groups consisted of all consecutive patients who received senile cataract surgery or intravitreal ranibizumab injection for treatment-naïve neovascular AMD, respectively. The AMD group received 3 monthly ranibizumab injections followed by monthly pro re nata for at least 12 months. Aqueous ANGPTL4 and vascular endothelial growth factor (VEGF) were measured at baseline and 4 weeks after the first injection. In the AMD group, best-corrected visual acuity, lesion area by fluorescein angiography, and central subfield thickness were measured at baseline and at 12 months. RESULTS: The AMD group (30 eyes) had higher baseline aqueous ANGPTL4 and VEGF levels than those of the control group (32 eyes) (both P < 0.001). Four weeks after the first injection, VEGF in the patients with AMD had dropped significantly (P < 0.001). Baseline ANGPTL4 correlated with the lesion area at baseline and at 12 months (P < 0.05, respectively), and also correlated with the frequency of anti-VEGF injections during 12 months (P = 0.008). CONCLUSION: Aqueous ANGPTL4 levels correlated with the lesion area and anti-VEGF treatment frequency. Angiopoietin-like 4 may be a potential diagnostic and/or therapeutic biomarker in the neovascular AMD.

Short-term Analysis of the Residual Volume of an Eye Drop Following 23-Gauge Microincision Vitrectomy Surgery.

PURPOSE: To evaluate the change of residual volume of eye drop after instillation in patients with 23-gauge microincision vitrectomy surgery (MIVS). METHODS: Patient who were treated 23-gauge MIVS from November 2014 to July 2015 were included. The residual volume was defined as the amount of remnant eye drop in patient's eyes after instillation, calculated as the difference between instillation volume and spilled volume of eye drop. Calculation of residual volume of eye drop was performed one day before surgery, and daily from postoperative day 1 to day 5. RESULTS: Forty consecutive patients were included. The residual volume of eye drop decreased from 30.3 ± 1.4 µL at baseline to 13.0 ± 1.5 µL at day 1, 18.3 ± 1.6 µL at day 2, 24.7 ± 1.5 µL at day 3, and 27.9 ± 1.4 µL in day 4, postoperatively (p < 0.001, respectively). The volume at postoperative day 5 was 29.4 ± 1.3 µL, but it was not different from the volume at baseline (p = 0.105). The change of residual volume was significantly correlated with postoperative chemosis (r = 0.672, p < 0.001) and effected by the number of quadrant with postoperative chemosis (p < 0.05). CONCLUSIONS: This study shows that postoperative residual volume of eye drop after instillation decreased until postoperative day 4, and postoperative chemosis affects the change of residual volume. Thus, checking proper use of eye drops and teaching about instillation technique by physician is necessary for patients with 23-gauge MIVS.

Association of Plasma Semaphorin 3A With Phenotypes of Diabetic Retinopathy and Nephropathy.

PURPOSE: To investigate whether diabetic retinopathy phenotypes and albuminuria are associated with the overexpression of plasma semaphorin 3A (Sema3A). METHODS: The study group with severe nonproliferative diabetic retinopathy (NPDR) or proliferative diabetic retinopathy (PDR), the diabetes without diabetic retinopathy group, and the control group without diabetes consisted of all consecutive patients who were scheduled to undergo intravitreal bevacizumab injection for treatment-naïve diabetic macular edema (DME) and senile cataract surgery, respectively. In all subjects, the plasma Sema3A levels before intravitreal bevacizumab injections or cataract surgery were measured by enzyme-linked immunosorbent assay. In the patients with DME, the capillary nonperfusion area (measured by fluorescein angiography), total macular volume (measured by spectral-domain optical coherence tomography), and the urine albumin-to-creatinine ratio were determined. RESULTS: Severe NPDR (57 eyes) and PDR groups (51 eyes) both had significantly higher Sema3A levels than the control (58 eyes) and diabetes without diabetic retinopathy groups (54 eyes) (P < 0.001). Moreover, the PDR group had higher Sema3A levels than the severe NPDR group (P < 0.001). Plasma Sema3A levels correlated positively with the retinal nonperfusion area size (r = 0.844, P = 0.004), total macular volume (r = 0.765, P = 0.005), and the urine albumin-to-creatinine ratio (r = 0.752, P < 0.001). When DME patients were divided into normo-, micro-, and macroalbuminuria groups, the macroalbuminuria group had significantly higher plasma Sema3A levels than the microalbuminuria group or the normoalbuminuria group (P = 0.002 and P < 0.001, respectively). CONCLUSIONS: The plasma Sema3A levels correlated significantly with the phenotypes of diabetic retinopathy and albuminuria. This suggests that Sema3A may be a potential biomarker for diabetic retinopathy and nephropathy.

Does Intravitreal Dexamethasone Implant Fragmentation Affect Clinical Outcomes in Macular Edema from Branch Retinal Vein Occlusion?

PURPOSE: The aim of this study was to evaluate the effect of intravitreal dexamethasone implant fragmentation on clinical outcomes in branch retinal vein occlusion (BRVO)-induced macular edema (ME). METHODS: All consecutive patients receiving an intravitreal dexamethasone implant for BRVO-induced ME were divided into two groups depending on whether the implant was intact or had fragmented into two or more pieces on postoperative day 1. Best-corrected visual acuity (BCVA), intraocular pressure (IOP), and central subfield thickness (CST) on spectral-domain optical coherence tomography were measured for 6 months. RESULTS: Among 68 patients, the implant was fragmented in 6 (8.8%) and intact in 62 (91.2%) eyes. The two groups did not differ in BCVA and CST at any time point (all p > 0.05). There was no difference in the ME recurrence rate, frequency of IOP elevation, and cataract progression between the two groups (all p > 0.05). CONCLUSION: Fragmentation seemed not to influence clinical outcomes of intravitreal dexamethasone implantation during 6 months or to alter the frequency of adverse events.

Aqueous Angiopoietin-Like 4 Levels Correlate With Nonperfusion Area and Macular Edema in Branch Retinal Vein Occlusion.

PURPOSE: To investigate whether macular edema (ME) due to branch retinal vein occlusion (BRVO) associates with retinal overexpression of angiopoietin-like 4 (ANGPTL4). The aqueous ANGPTL4 and vascular endothelial growth factor (VEGF) levels in patients with ME due to BRVO were measured, and the relationships between ANGPTL4 levels and the degree of retinal ischemia and edema were determined. METHODS: The study and control groups consisted of all consecutive patients who were scheduled to undergo intravitreal bevacizumab injection for treatment-naïve BRVO with ME and senile cataract surgery, respectively. The study group was divided into the major BRVO and macular BRVO subgroups on the basis of the involved retinal area. The aqueous ANGPTL4 and VEGF levels were measured by enzyme-linked immunosorbent assay. In the patients with BRVO, capillary nonperfusion area by fluorescein angiography and central subfield macular thickness (CSMT) and total macular volume (TMV) by spectral-domain optical coherence tomography were determined. RESULTS: Patients with ME due to BRVO (50 eyes) had higher aqueous ANGPTL4 and VEGF levels than the controls (61 eyes) (both P < 0.001). The major BRVO had higher ANGPTL4 and VEGF levels than the macular BRVO (both P < 0.001). The aqueous ANGPTL4 levels of all BRVO patients correlated positively with nonperfusion area (r = 0.901, P < 0.001), CSMT (r = 0.574, P < 0.001), and TMV (r = 0.453, P = 0.001), even after adjustment for VEGF levels. CONCLUSIONS: The aqueous ANGPTL4 levels correlated significantly with phenotypes of BRVO with ME. This suggests that ANGPTL4 may be a candidate biomarker and treatment target in ischemia-induced retinopathies, including BRVO.

Recurrence of macular edema in eyes with branch retinal vein occlusion changes the diameter of unaffected retinal vessels.

PURPOSE: To measure unaffected retinal vessel diameter in eyes with macular edema (ME) secondary to branch retinal vein occlusion (BRVO) after intravitreal injection with bevacizumab (IVB). METHODS: Patients with BRVO-induced ME who responded to IVB were assessed at baseline and 1, 3, and 6 months. In both eyes, the diameters of the largest arteriole and venule in all quadrants (except occlusion quadrant) were measured by using a computer-assisted method. The same vessels chosen at baseline were measured at each follow-up examination. RESULTS: Forty-two eyes were participated. At baseline, venular diameters of unaffected quadrants in eyes with BRVO were larger than the venules in the corresponding quadrant of the fellow eyes (p < 0.05, respectively). The venular diameters in all quadrants of the affected eyes decreased significantly relative to baseline after IVB (p < 0.05 respectively). Twenty-two eyes (52.4 %) developed recurrent ME. On recurrence at 3 (n = 15, 35.7 %) or 6 months (n = 7, 16.7 %), the unaffected venular diameters increased significantly (p < 0.05 respectively). These diameters again decreased significantly after a second IVB (p < 0.05 respectively). CONCLUSION: Unaffected retinal venular diameters associate with the course of BRVO with ME. This may help elucidate the pathological mechanism underlying BRVO.

VARIATION OF 24-HOUR INTRAOCULAR PRESSURE IN SILICONE OIL-FILLED EYES.

PURPOSE: To evaluate the variation of 24-hour intraocular pressure (IOP) in silicone oil (SO)-filled eyes. METHODS: Prospective, nonrandomized comparative case series of 42 eyes of 21 patients, each with an SO-filled eye after vitrectomy. The fellow eyes served as controls. Each subject slept the usual 8 hours, and IOPs were measured at 4-hour intervals over 24 hours, twice before sleep (5:30 and 9:30 PM), twice during sleep (1:30 and 5:30 AM), and twice after sleep (9.30 AM and 1:30 PM). Intraocular pressure was measured in the sitting position using a Goldmann applanation tonometer. The SO-filled eyes and fellow eyes were compared with respect to diurnal-to-nocturnal and nocturnal-to-diurnal IOP changes. RESULTS: At all 6 time points, SO-filled eyes had higher mean IOPs than fellow eyes (all P < 0.05). For both groups, mean nocturnal IOP was higher than mean diurnal IOP (both P < 0.001). Changes in diurnal-to-nocturnal IOP and nocturnal-to-diurnal IOP between SO-filled eyes and fellow eyes did not differ significantly (P > 0.05, respectively). The peak IOP occurred in the nocturnal period for all fellow eyes and for 94.7% of SO-filled eyes. CONCLUSION: The IOP of SO-filled eyes varied over a 24-hour period, peaking largely in the nocturnal period, as observed for the IOP of fellow eyes.

Aqueous Levels of Angiopoietin-like 4 and Semaphorin 3E Correlate with Nonperfusion Area and Macular Volume in Diabetic Retinopathy.

OBJECTIVE: To investigate the aqueous levels of angiopoietin-like 4 (ANGPTL4), semaphorin 3E (Sema3E), and vascular endothelial growth factor (VEGF) in patients with diabetic retinopathy and to ascertain their association with diabetic retinopathy phenotypes. DESIGN: Prospective, nonrandomized, comparative case series. PARTICIPANTS: Of all 104 consecutive patients (104 eyes) who had intravitreal anti-VEGF injections from April 2012 through April 2013 for diabetic macular edema (DME), 51 had severe nonproliferative diabetic retinopathy (NPDR) and 53 had proliferative diabetic retinopathy (PDR). The controls were 54 consecutive nondiabetic patients who had undergone cataract surgery (54 eyes) during the same period. METHODS: The ANGPTL4, Sema3E, and VEGF levels in aqueous humor samples obtained before intravitreal injections were measured by enzyme-linked immunosorbent assay. Capillary nonperfusion area (NPA) was calculated from encircled angiography using the 7 standard field images described in the Early Treatment Diabetic Retinopathy Study protocol. Total macular volume (TMV) was measured by spectral-domain optical coherence tomography. MAIN OUTCOME MEASURES: Aqueous ANGPTL4, Sema3E, and VEGF levels in severe NPDR, PDR, and control groups and their correlations with each other, NPA, and TMV. RESULTS: The severe NPDR and PDR groups had higher aqueous levels of ANGPTL4 and VEGF than the control group (all P < 0.001). The PDR group had higher ANGPTL4 and VEGF levels than the severe NPDR group (both P < 0.001). The aqueous ANGPTL4 levels of all diabetic retinopathy patients correlated positively with NPA (r = 0.820, P = 0.003) and TMV (r = 0.824, P < 0.001). The control group had higher aqueous Sema3E levels than the NPDR and PDR groups (both P < 0.001). Aqueous Sema3E levels correlated negatively with VEGF levels in all subjects (r = -0.57, P = 0.025). CONCLUSIONS: The ANGPTL4 may be a candidate target in DME treatment and a biomarker of ischemic-induced retinopathy, including diabetic retinopathy.

Two cases of CHARGE syndrome with multiple congenital anomalies.

We report on two cases of bilateral chorioretinal colobomas with ocular anomalies in patients with CHARGE syndrome. In the first case, a female infant was born at 36 + 5 weeks gestation. At birth, the patient demonstrated a small left eye. Slit-lamp examination revealed colobomas of both irises. Fundus examination showed both chorioretinal colobomas. Brain magnetic resonance imaging (MRI) showed left microphthalmia. Systemic evaluation revealed multiple congenital anomalies: benign external hydrocephalus, esophageal atresia with imperforate anus, atrial septal defect (ASD), ventricular septal defect, patent ductus arteriosis (PDA), and right mild hydronephrosis. In the second case, a male infant was born at 39 + 5 weeks gestation and demonstrated a dysmorphic appearance with an irregular left pupil and ptosis. Fundus examination of both eyes showed large chorioretinal colobomas involving the optic disc and posterior pole. The patient had multi-organ anomalies: right facial palsy, a left short, wide ear with a small lobe, congenital heart defects, such as ASD and PDA, left renal atresia, seizure disorder, and micropenis. Both cases revealed multiple anomalies including nearly all major and minor criteria of CHARGE syndrome which could be life-threatening to neonates. Thus, all neonates with ocular colobomas should have fully and detailed systemic examinations checking all minor criteria and even occasional findings of CHARGE syndrome.

One-year follow-up of macular ganglion cell layer and peripapillary retinal nerve fibre layer thickness changes after panretinal photocoagulation.

BACKGROUND/AIMS: To assess the changes of ganglion cell-inner plexiform layer (GCIPL) thickness, retinal nerve fibre layer (RNFL) thickness, and central subfield thickness (CST) after panretinal photocoagulation (PRP) in diabetic retinopathy for 1 year. METHODS: This prospective, interventional case series study examined 35 patients (35 eyes) undergoing PRP, who were diagnosed with severe non-proliferative diabetic retinopathy to non-high-risk proliferative diabetic retinopathy without macular oedema. Macular GCIPL thickness, CST, and peripapillary RNFL thickness were measured by spectral-domain optical coherence tomography at baseline, and then at 1, 3, 6, 9 and 12 months after PRP. RESULTS: Macular GCIPL and peripapillary RNFL (average and all sections) thickness at each follow-up increased significantly from the baseline (p<0.001, respectively). The average, superior and inferior RNFL thickness at 12 months after PRP decreased significantly compared to the 1-month post-PRP (p=0.007, p=0.028 and p=0.025). The average GCIPL and temporal RNFL thickness showed a significant correlation at each follow-up (p<0.001, respectively). CST at each follow-up increased significantly from the baseline (p<0.001, respectively). CONCLUSIONS: The macular GCIPL and peripapillary RNFL thickness increased throughout the 1-year post-PRP. Furthermore, the macular GCIPL and temporal RNFL thickness showed a significant correlation throughout the 1 year of follow-up.

Association of plasma malondialdehyde with ARMS2 genetic variants and phenotypes in polypoidal choroidal vasculopathy and age-related macular degeneration.

PURPOSE: To evaluate the relationships between plasma malondialdehyde (MDA) level and ARMS2 variants and phenotypes in patients with polypoidal choroidal vasculopathy (PCV) and neovascular age-related macular degeneration (nAMD). METHODS: This study is a retrospective case-control study. Plasma MDA was measured in 84 controls, 62 patients with PCV, and 42 patients with nAMD. Participants were genotyped for ARMS2 polymorphism. Phenotypes including bilaterality and greatest linear dimension based on fluorescein angiography (FA-GLD) and indocyanine green angiography (ICGA-GLD), were evaluated. RESULTS: Plasma MDA in the PCV and nAMD groups was higher than in the control group (P < 0.001, respectively). For ARMS2 variants, plasma MDA of homozygous high-risk genotype (TT) was higher than that of homozygous low-risk genotype (GG) in all groups (P < 0.001, respectively). Plasma MDA was higher in homozygous high-risk genotype than in heterozygous genotype in the control, PCV, and nAMD groups (P = 0.021, 0.002, and 0.004, respectively). In the nAMD group, there was a correlation between plasma MDA and both FA-GLD (r = 0.418, P = 0.006) and ICGA-GLD (r = 0.329, P = 0.033). There was a difference in plasma MDA between patients with unilateral and bilateral lesions in both PCV and nAMD (P = 0.017 and 0.019, respectively). CONCLUSION: This study revealed significant relationships between the plasma MDA level and ARMS2 variants and phenotypes in PCV and nAMD.

Comparative study of corneal wetting agents during 25-gauge microincision vitrectomy surgery under a noncontact wide-angle viewing system.

BACKGROUND AND OBJECTIVE: To compare the effects of corneal wetting agents during 25-gauge microincision vitrectomy surgery (MIVS) under a binocular indirect ophthalmic microscope system. MATERIALS AND METHODS: This prospective, randomized, comparative study included 45 eyes undergoing 25-gauge MIVS. The randomly assigned corneal wetting agents were balanced salt solution, ProVisc, and DisCoVisc. The main outcome measures were the frequency of applications, the duration of each application, and the corneal surface status including corneal fluorescein staining score postoperatively. RESULTS: The mean frequency of applications was higher for balanced salt solution (13.6 ± 4.3) than ProVisc (2.7 ± 1.0) or DisCoVisc (1.7 ± 0.5) (P < .001). The duration of each application was longer for DisCoVisc (29.8 ± 6.0 minutes) than balanced salt solution (3.7 ± 1.1 minutes) or ProVisc (17.6 ± 3.6 minutes) (P < .001). The fluorescein staining score was higher for balanced salt solution until 7 days postoperatively (P < .001). CONCLUSION: ProVisc and DisCoVisc could be more effective corneal wetting agents than balanced salt solution by minimizing the frequency of intraoperative application and postoperative corneal injury.

Pharmacogenetic association with early response to intravitreal ranibizumab for age-related macular degeneration in a Korean population.

PURPOSE: To determine whether genetic factors that influence age-related macular degeneration (AMD) have an early pharmacogenetic effect on treating exudative AMD with ranibizumab in a Korean population. METHODS: A retrospective study of 102 patients (70 with typical neovascular AMD and 32 with polypoidal choroidal vasculopathy) with exudative AMD treated with intravitreal ranibizumab monotherapy was conducted. Optical coherence tomography, fluorescein, and indocyanine green angiography were taken at the baseline. The best-corrected visual acuity (BCVA) and the central subfield macular thickness (CSMT) were recorded at the baseline and at each monthly visit. The genotypes of the polymorphisms in the known AMD susceptibility loci (CFH, AMRS2, HTRA1, VEGFA, and KDR) were determined, and association between their frequencies and the changes in the BCVA and the CSMT were evaluated. RESULTS: The mean baseline visual acuity was 0.96 ± 0.59 logMAR (approximately 20/200 in the Snellen equivalent), and the mean number of injections was 3.87 before the month 6 visit. No association was observed between the change in BCVA and each genotype. For the changes in the CSMT, a significant difference was observed only with the VEGF-A (rs833069) gene. The decrease in the CSMT at month 3 for the major allele homozygote AA genotype, the heterozygote AG genotype, and the risk allele homozygote GG genotype was 25.66 ± 85.40, 86.93 ± 92.31, and 85.30 ± 105.30 µm, respectively (p=0.012, p=0.044, and p=0.002 for AG, GG, and combined AG or GG genotype, respectively, compared to the AA genotype). This trend was maintained until month 6. CONCLUSIONS: The VEGF-A (rs833069) polymorphism showed a significant association with the anatomic response to intravitreal ranibizumab. No significant difference was found between the genotype of the potential risk polymorphism for development of AMD and the early visual improvement after intravitreal ranibizumab.

Two-year results of AcrySof toric intraocular lens implantation in patients with combined microincision vitrectomy surgery and phacoemulsification.

AIM: To evaluate the effects and stability of AcrySof toric intraocular lens (IOL) implantation in patients who had combined microincision vitrectomy surgery (MIVS) and phacoemulsification for vitreoretinal diseases and cataract with corneal astigmatism. METHODS: A retrospective comparative study with 20 patients (20 eyes) who had combined 23-gauge MIVS and phacoemulsification with regular corneal astigmatism (>1.00 dioptres) was done. 10 eyes had toric IOL and 10 eyes had non-toric IOL implantation. The main outcome measures were uncorrected visual acuity (UCVA), refractive cylinder and toric IOL axis rotation at postoperative months 1, 6, 12, 18 and 24. RESULTS: The mean UCVA of toric IOL was better than non-toric IOL at each postoperative period (p=0.019, 0.001, 0.007, 0.004 and 0.001, respectively). The mean absolute residual refractive cylinder of toric IOL was less than non-toric IOL at each postoperative period (p=0.001, <0.001, <0.001, <0.001 and <0.001, respectively). At month 24, the mean toric IOL axis rotation was 3.3 ± 2.1°, which was within 5° in 80% and within 10° in 100%. CONCLUSIONS: Toric IOL implantation could be an effective method of correcting corneal astigmatism in patients who have vitreoretinal diseases and cataract. The toric IOL showed good rotational stability, even in vitrectomised eyes for 24 months.

Clinical characteristics of polypoidal choroidal vasculopathy associated with chronic central serous chorioretionopathy.

PURPOSE: To investigate the clinical characteristics of polypoidal choroidal vasculopathy (PCV) associated with chronic central serous chorioretinopathy (CSC). METHODS: We retrospectively reviewed the medical records of 246 PCV patients (283 eyes) between July 2004 and August 2009 and investigated the clinical characteristics of the PCV patients who had specific fundus findings of chronic CSC. RESULTS: Among PCV patients, 13 eyes (4.6%) of 13 PCV patients (5.3%) had fundus findings of chronic CSC. All of the PCV lesions had a solitary polyp located outside the atrophic retina, predominantly in the macular area (84.6%), most showed an exudative pattern (69.2%) and there were a few that showed a hemorrhagic pattern (30.8%). All of the lesions were smaller than 1 disc diameter. Most of the PCV lesions (76.9%) were cured with less than two treatments in a short period of 6.4 ± 1.9 months; however, visual acuity deteriorated (61.5%) or was not changed (30.8%) in most of the cases. CONCLUSIONS: The PCV associated with chronic CSC had several clinical features such as a small exudative retinal lesion with a solitary polyp and frequent involvement of the macular area. Even though there was poor visual outcome due to the atrophic change, all of the PCV lesions were easily resolved in a short period with a simple treatment course and no recurrence.