Jeeyun Ahn

Age-Related Macular Degeneration: Prevalence and Risk Factors from Korean National Health and Nutrition Examination Survey, 2008 through 2011

OBJECTIVE To investigate the prevalence and risk factors of age-related macular degeneration (AMD) in the Korean population. DESIGN A cross-sectional study using a complex, stratified, multistage, probability-cluster survey, which can produce nationally representative estimates. PARTICIPANTS Using the database of Korean National Health and Nutrition Examination Survey from 2008 through 2011, 14 352 participants 40 years of age or older with gradable fundus photographs were included. METHODS Age-related macular degeneration was determined by fundus photograph. Prevalences of AMDs were estimated. Risk factor analyses were conducted using logistic regression analyses (LRAs). MAIN OUTCOME MEASURES Prevalence and risk factors of AMD. RESULTS The prevalence of AMD was 6.62% (95% confidence interval [CI], 6.15%-7.09%) in the Korean population: 6.02% (95% CI, 5.56%-6.48%) were early AMD and 0.60% (95% CI, 0.45%-0.75%) were late AMD. The prevalence of early AMD in women (6.73%; 95% CI, 6.11%-7.35%) was higher than that in men (5.25%; 95% CI, 4.61%-5.89%; P<0.001), and the prevalence of late AMD in women (0.37%; 95% CI, 0.22%-0.52%) was lower than that in men (0.85%; 95% CI, 0.59%-1.12%; P<0.001). However, in multiple LRAs both early and late AMD had no association with gender, house income, residence, sun exposure, or systemic comorbidities, including hypertension, diabetes mellitus, and cardiovascular diseases. Early AMD had positive associations with older age groups (P<0.001), lower education (P = 0.027), occupation (P<0.001), anemia (P = 0.027), hepatitis B surface antigen carrier status (P<0.001), not being overweight (body mass index [BMI], P = 0.032; waist circumference, P = 0.041, in separate analyses), and higher serum high-density lipoprotein (HDL) level (P = 0.046), but not with smoking status. Late AMD had positive associations with age groups (P<0.001), current smokers (P = 0.022), and lower BMI (P = 0.037). CONCLUSIONS The results suggest that there are 1.21 million individuals with early AMD and 121 000 individuals with late AMD in Korea. Nonoverweight status and higher HDL levels, generally assumed as positive health indicators, as well as anemia and hepatitis B infection had harmful associations with AMD in our study, implying a possible different pathophysiologic process of AMD in Asians compared with that of white persons.

Cognitive Impairment in Age-related Macular Degeneration and Geographic Atrophy

PURPOSE To investigate cognitive function in patients with early and late age-related macular degeneration (AMD) compared with an elderly, community-dwelling Korean population without AMD. DESIGN Case-control study. PARTICIPANTS We enrolled 170 AMD patients and 190 non-AMD community-based controls. METHODS A comprehensive battery for cognitive function evaluation consisting of 15 psychological tests, including a depression evaluation test, was used. Cognitive function scores were adjusted for age, gender, education, and visual acuity (VA). We categorized AMD as early AMD, exudative AMD, or geographic atrophy. MAIN OUTCOME MEASURES The primary outcome measure was the degree of cognitive impairment, as assessed by the Korean versions of the Consortium to Establish a Registry for Alzheimers Disease Neuropsychological Assessment Battery, Benton Visual Retention Test, and Digit Span Test Forward and Backward. RESULTS Patients with AMD showed lower global cognition scores than did normal controls (mean Mini-Mental State Examination [MMSE] score, 24.97 vs 25.99; P<0.001). Among cognitive functions, visuospatial function, verbal memory, visual memory, and frontal function were impaired in AMD patients relative to normal controls. The rate of mild cognitive impairment (MCI) was higher in AMD patients than in controls (52.4% vs 26.8%; P<0.001), with an odds ratio (OR) of 3.127 (95% confidence interval, 1.855-5.271) after adjustment for age, education, and VA. Geographic atrophy was associated with the highest risk of MCI (OR, 4.431; 95% confidence interval, 1.413-13.898) and a clinically significant reduction in MMSE scores (23.42) relative to the controls. There was a trend of worsening cognitive function test scores from the controls to the early AMD, then the exudative AMD, and finally the geographic atrophy patients, after adjustment for covariates. AMD patients with poor VA (≤20/100) had 6 times the risk of MCI as AMD patients with good or moderate VA (>20/100). CONCLUSIONS Patients with AMD, especially those with the geographic atrophy subtype, are at greater risk for cognitive impairment than are non-AMD control subjects. In the visual rehabilitation of AMD patients, potential cognitive impairment should be taken into consideration.

Intraocular Pharmacokinetics of Ranibizumab in Vitrectomized Versus Nonvitrectomized Eyes

PURPOSE To analyze the intraocular pharmacokinetic properties of intravitreally injected ranibizumab in vitrectomized and nonvitrectomized rabbit eyes. METHODS A procedure consisting of 25-gauge pars plana vitrectomy without lensectomy and posterior vitreous detachment was performed in 18 rabbit eyes, and 18 nonvitrectomized rabbit eyes served as controls. Ranibizumab (0.25 mg/0.025 mL) was intravitreally injected in all the vitrectomized and nonvitrectomized eyes. The eyes were enucleated at 1 hour or 1, 2, 5, 14, or 30 days after the intravitreal injections and frozen at -80°C. Ranibizumab concentrations in the vitreous, aqueous humor, and retina were determined using indirect enzyme-linked immunosorbent assay. RESULTS Vitreous clearance of ranibizumab showed a 2-phase elimination. The vitrectomized and nonvitrectomized eyes showed comparable rates of vitreous clearance of ranibizumab. The vitreous half-life of ranibizumab for up to 14 days was 2.51 and 2.75 days in vitrectomized and nonvitrectomized eyes, respectively. Throughout the 30-day period after intravitreal injection, there were no statistically significant differences between the concentrations of ranibizumab in the vitreous, aqueous humor, and retina of vitrectomized eyes and those in nonvitrectomized eyes. Concentrations of ranibizumab in the vitreous peaked 1 hour after injection, with a mean concentration of 118.01 and 91.61 μg/mL in vitrectomized and nonvitrectomized eyes, respectively. The elimination rate constant of intravitreal ranibizumab in 1-phase analyses showed only a 9% increase in vitrectomized eyes compared to nonvitrectomized eyes. CONCLUSIONS Overall intraocular pharmacokinetic properties of ranibizumab in vitrectomized eyes were similar to those in nonvitrectomized eyes. Our data do not support the use of different dosing regimens of ranibizumab in vitrectomized eyes.

The Effect of Adjunctive Intravitreal Bevacizumab for Preventing Postvitrectomy Hemorrhage in Proliferative Diabetic Retinopathy

OBJECTIVE To assess the effects of preoperative and intraoperative intravitreal bevacizumab (IVB) injection on the incidence of postoperative vitreous hemorrhage (VH) after vitrectomy for proliferative diabetic retinopathy (PDR). DESIGN Prospective, randomized, clinical trial. PARTICIPANTS One hundred seven eyes of 91 patients undergoing pars plana vitrectomy (PPV) for the management of PDR-related complications were enrolled. METHODS One hundred seven cases were assigned randomly to either group 1 (intravitreal 1.25 mg/0.05 ml bevacizumab injection 1 to 14 days before PPV), group 2 (intravitreal 1.25 mg/0.05 ml bevacizumab injection at the end of PPV), or group 3 (no IVB injection). MAIN OUTCOME MEASURES The primary outcome was the incidence of early (≤ 4 weeks) and late (> 4 weeks) recurrent VH. Secondary outcome measures were the initial time of vitreous clearing (ITVC) and best-corrected visual acuity (BCVA) at 6 months after surgery. RESULTS The incidences of early recurrent VH were 22.2%, 10.8%, and 32.4% in groups 1, 2, and 3, respectively (P = 0.087). A subgroup pairwise analysis showed significantly decreased early VH incidence in group 2 compared with that of group 3 (P = 0.026). The incidences of late recurrent VH were 11.1%, 16.2%, and 14.7% in groups 1, 2, and 3, respectively (P = 0.813). The ITVC in groups 1, 2, and 3 were 26.4 ± 42.5 days, 10.3 ± 8.2 days, and 25.2 ± 26.1 days, respectively. The ITVC was significantly shorter in group 2 compared with that in groups 1 and 3 (P = 0.045 and P = 0.015, respectively). The BCVA at 6 months after surgery did not differ significantly among the 3 groups (P = 0.418). CONCLUSIONS This study found no substantial evidence to support the adjunctive use of preoperative IVB to reduce postoperative recurrence of VH in vitrectomy for PDR. For select cases in which adjunctive IVB use is considered, intraoperative administration seems to be the better option for reducing postoperative VH. FINANCIAL DISCLOSURE(S) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Prevalence and Risk Factors of Age-Related Macular Degeneration in Korea: The Korea National Health and Nutrition Examination Survey 2010-2011

PURPOSE To investigate the prevalence and risk factors of age-related macular degeneration (AMD) in the general Korean adult population. METHODS The study involved a nationally representative Korean population from the 2010 to 2011 Korea National Health and Nutrition Examination Survey. A total of 7899 subjects ≥ 40 years old participated in health interviews, physical examinations, and ophthalmologic assessment including fundus photography. RESULTS The overall prevalence of early AMD was estimated at 6.7% (95% confidence interval [CI], 6.1-7.4), and that of late AMD was estimated at 0.7% (95% CI, 0.5-0.9), which included 0.5% prevalence of neovascular AMD and 0.2% prevalence of geographic atrophy. The prevalence rates of early and late AMD among participants aged ≥ 65 years were 16.9% and 1.8%, respectively. Hyperopia was positively associated with the presence of any AMD type (odds ratio [OR], 1.08 for every 1 diopter increase). In multivariate analyses, significant risk factors for the presence of any AMD type were age, serum high-density lipoprotein (HDL) level, serum gamma-glutamyl transferase (GGT) level, and hepatitis B surface antigen (HBsAg) serum positivity (OR, 2.26). The risk factors for late AMD included age, ever-smoking history (OR, 2.18), serum GGT level, and systolic blood pressure. CONCLUSIONS The prevalence of AMD in Korea was similar to the prevalence of pooled Asian and Western populations. Age and serum GGT level were strongly associated with both the presence of any AMD and late AMD. Additionally, serum HDL level, HBsAg serum positivity, ever-smoking history, and systolic blood pressure were identified as risk factors for AMD.

Pharmacokinetics of Intravitreally Injected Bevacizumab in Vitrectomized Eyes

PURPOSE To compare the pharmacokinetics (PKs) of intravitreally injected bevacizumab in vitrectomized versus nonvitrectomized control rabbit eyes. METHODS Twenty-five-gauge pars plana vitrectomy without lensectomy was performed in 17 right rabbit eyes (V) and 18 nonvitrectomized right rabbit eyes served as controls (C). After 1.25 mg/0.05 mL intravitreal bevacizumab (IVB) injections, eyes were enucleated at 1 h, 1, 2, 5, 14, and 30 days after the injection and immediately frozen at -80°C. Bevacizumab concentrations were determined after separation of frozen vitreous and aqueous humor (AH) compartments using indirect enzyme-linked immunosorbent assay. Bevacizumab concentration-time data were analyzed to obtain PK data. RESULTS Vitreous clearance of IVB consisted of 2 phases, the first fast distribution and second slow elimination phase. Clearance of IVB was accelerated in V eyes only during the first phase and not in the second phase. The vitreous concentration percent ratios between V and C eyes were 94.7% (1 h), 70.5% (1 day), 89.2% (2 days), 94.2% (5 days), 99.2% (14 days), and 79.1% (30 days). Overall vitreous half-lives were 6.99 and 7.06 days for V and C eyes, respectively (1.6-h difference). CONCLUSION Overall IVB PKs in rabbit eyes after vitrectomy without lensectomy are not substantially different from nonvitrectomized control eyes.

Clinical features and course of ocular toxocariasis in adults.

Purpose To investigate the clinical features, clinical course of granuloma, serologic findings, treatment outcome, and probable infection sources in adult patients with ocular toxocariasis (OT). Methods In this retrospective cohort study, we examined 101 adult patients diagnosed clinically and serologically with OT. Serial fundus photographs and spectral domain optical coherence tomography images of all the patients were reviewed. A clinic-based case-control study on pet ownership, occupation, and raw meat ingestion history was performed to investigate the possible infection sources. Results Among the patients diagnosed clinically and serologically with OT, 69.6% showed elevated immunoglobulin E (IgE) levels. Granuloma in OT involved all retinal layers and several vitreoretinal comorbidities were noted depending on the location of granuloma: posterior pole granuloma was associated with epiretinal membrane and retinal nerve fiber layer defects, whereas peripheral granuloma was associated with vitreous opacity. Intraocular migration of granuloma was observed in 15 of 93 patients (16.1%). Treatment with albendazole (400 mg twice a day for 2 weeks) and corticosteroids (oral prednisolone; 0.5–1 mg/kg/day) resulted in comparable outcomes to patients on corticosteroid monotherapy; however, the 6-month recurrence rate in patients treated with combined therapy (17.4%) was significantly lower than that in patients treated with corticosteroid monotherapy (54.5%, P = 0.045). Ingestion of raw cow liver (80.8%) or meat (71.2%) was significantly more common in OT patients than healthy controls. Conclusions Our study discusses the diagnosis, treatment, and prevention strategies for OT. Evaluation of total IgE, in addition to anti-toxocara antibody, can assist in the serologic diagnosis of OT. Combined albendazole and corticosteroid therapy may reduce intraocular inflammation and recurrence. Migrating feature of granuloma is clinically important and may further suggest the diagnosis of OT. Clinicians need to carefully examine comorbid conditions for OT. OT may be associated with ingestion of uncooked meat, especially raw cow liver, in adult patients.

Photoreceptor change and visual outcome after idiopathic epiretinal membrane removal with or without additional internal limiting membrane peeling.

Purpose: To compare the postoperative photoreceptor status and visual outcome after epiretinal membrane removal with or without additional internal limiting membrane (ILM) peeling. Methods: Medical records of 40 eyes from 37 patients undergoing epiretinal membrane removal with residual ILM peeling (additional ILM peeling group) and 69 eyes from 65 patients undergoing epiretinal membrane removal without additional ILM peeling (no additional peeling group) were reviewed. The length of defects in cone outer segment tips, inner segment/outer segment junction, and external limiting membrane line were measured using spectral domain optical coherence tomography images of the fovea before and at 1, 3, 6, and 12 months after the surgery. Results: Cone outer segment tips and inner segment/outer segment junction line defects were most severe at postoperative 1 month and gradually restored at 12 months postoperatively. The cone outer segment tips line defect in the additional ILM peeling group was significantly greater than that in the no additional peeling group at postoperative 1 month (P = 0.006), and best-corrected visual acuity was significantly worse in the former group at the same month (P = 0.001). There was no significant difference in the defect size and best-corrected visual acuity at subsequent visits and recurrence rates between the two groups. Conclusion: Patients who received epiretinal membrane surgery without additional ILM peeling showed better visual and anatomical outcome than those with additional ILM peeling at postoperative 1 month. However, surgical outcomes were comparable between the two groups, thereafter. In terms of visual outcome and photoreceptor integrity, additional ILM peeling may not be an essential procedure.

Elevated Systemic Neutrophil Count in Diabetic Retinopathy and Diabetes: A Hospital-Based Cross-sectional Study of 30,793 Korean Subjects

PURPOSE To evaluate the association between systemic parameters including inflammatory markers and diabetic retinopathy (DR). METHODS This was a cross-sectional study enrolling 30,793 persons who visited a health care center for a medical checkup. Diabetic patients were classified into five DR groups: no DR; mild, moderate, or severe nonproliferative DR, and proliferative DR. A full laboratory workup and comprehensive medical data on the subjects were obtained and used for analysis. RESULTS The mean (SD) age of the participants was 47.4 (11.9) years (range, 18-90) and the male-to-female ratio was 55.7:44.3. The prevalence of diabetes and DR were 6.6% (2,020/30,793) and 5.3% (108/2,020), respectively. Among inflammatory markers, the mean absolute neutrophil count (ANC; per microliter) was significantly higher in the DR than in the non-DR group (3900 vs. 3566; P = 0.0143) and in diabetic than in nondiabetic subjects (3583 vs. 3262; P < 0.0001). Subjects in the fourth quintiles of ANC showed 2.7 odds of having DR by multivariate analysis, and there was a linear trend in the odds ratios according to increasing ANC levels. The level of ANC and the ANC/leukocyte ratio also demonstrated a linearly increasing trend with the severity of DR, even after adjustment for other clinical factors, including HbA1c. Among significant risk factors of DR, ANC showed the second strongest predictive power for DR (AUROC = 0.590) after HbA1C (0.624). CONCLUSIONS Elevated systemic neutrophil count is associated with the presence and severity of DR as well as diabetes. This result indicates that systemic subclinical inflammation is related with DR, and neutrophil-mediated inflammation may play an important role in the pathogenesis of DR.

Efficacy and Safety of Intra-Arterial Thrombolysis in Central Retinal Artery Occlusion

PURPOSE To investigate the efficacy and safety of intra-arterial thrombolysis (IAT) for acute central retinal artery occlusion (CRAO). METHODS Records from 101 CRAO patients treated with either IAT (n = 57) or standard treatment (ST; n = 44) were retrospectively reviewed. ST consisted of ocular massage and intraocular pressure-lowering agents. We used fundoscopic and angiographic findings to categorize CRAO as incomplete (diminished visual acuity [VA] with slight retinal edema, slight cherry-red spot), subtotal (severe VA reduction, cherry-red spot, distinct retinal edema), or total (massive edema, occluded perimacular arterioles, additional choroidal blood flow interruption). One-month and final best-corrected VA (BCVA) of the IAT group were compared with those of the ST group. Early (≤3-day) and final (1-month) reperfusion (improvement of retinal perfusion) rates were compared between groups. Subgroup analyses were performed according to CRAO stage. RESULTS Overall, VA did not significantly differ between groups, but early reperfusion was greater in the IAT group (74.1% vs. 42.9%, P = 0.005). In incomplete CRAO, the IAT group exhibited greater visual improvement after 1 month (1.08 ± 0.21 vs. 0.23 ± 0.26 logarithmic values of the minimum angle of resolution [logMAR], P < 0.001) and at the final visit (1.08 ± 0.53 vs. 0.08 ± 0.57 logMAR, P < 0.001). However, in subtotal and total CRAO, no significant differences in visual outcomes were observed between groups. IAT resulted in clinically insignificant cerebral infarcts, detectable on brain imaging, in 8% of patients. Hemorrhagic transformation was not noted. CONCLUSIONS The IAT treatment may provide early restoration of retinal perfusion and offer functional benefits in the management of incomplete CRAO.