Atsuro Uchida

Predictive factors for non-response to intravitreal ranibizumab treatment in age-related macular degeneration

Background/aims To study the initial characteristics and response to intravitreal ranibizumab (IVR) treatment of age-related macular degeneration (AMD). Methods We reviewed the clinical records of 141 eyes in 141 AMD patients who received monthly IVR for 3 months and thereafter pro re nata (PRN) injections for 9 months as the first treatment for AMD. Patients whose best corrected visual acuity (BCVA) worsened at month 12, and those with increased exudative fundus findings after IVR or an increased central retinal thickness of more than 100 μm at month 12, were considered to be non-responders as judged by BCVA and fundus findings, respectively. Non-responders’ initial characteristics were analysed using logistic regression models. Results 14.9% of eyes were non-responders as judged by BCVA, and 17.0% were non-responders as judged by fundus findings. Initial fibrovascular pigment epithelial detachment (PED) (OR 22.9, 95% CI 2.61 to 201) and serous PED (OR 4.12, 95% CI 1.08 to 15.8) were associated with non-response as judged by BCVA. Initial fibrovascular PED (OR 33.5, 95% CI 2.95 to 381) and type 1 choroidal neovascularization (OR 6.46, 95% CI 1.39 to 30.0) were associated with non-response, as judged by fundus findings. Conclusions Although most AMD responded to IVR, non-responders had initial clinical characteristics that might be informative for managing their treatment.

Association of serum lipids with macular thickness and volume in type 2 diabetes without diabetic macular edema

PURPOSE To assess the relationship between macular thickness and volume as characterized by optical coherence tomography (OCT) and known risk factors for diabetic retinopathy (DR) or macular edema (DME) in type 2 diabetic patients with no DME. METHODS Seventy-four patients with type 2 diabetes without DME and no or only minimal DR (n = 67 with no DR; n = 7 with minimal DR; mean age, 59.5 years) were recruited at a tertiary eye hospital. Central subfield macular thickness (CSMT; circle of 500-μm radius) and central subfield macular volume (CSMV) were measured using spectral-domain OCT. Associations between OCT parameters and known risk factors for DR were examined using multiple linear regression models. RESULTS The mean CSMT and CSMV values were 273.7 ± 17.8 μm and 0.215 ± 0.015 mm(3), respectively. After adjusting for age, sex, duration of diabetes, hemoglobin A1c, and urine protein, low-density lipoprotein (LDL) cholesterol was positively associated with CSMT and CSMV; each 1 mmol/L increase in LDL was associated with a mean increase in CSMT of 6.52 μm (95% confidence interval [CI], 1.96-11.08; P = 0.006) and a mean increase in CSMV of 0.0047 mm(3) (95% CI, 0.001-0.0085; P = 0.015). CONCLUSIONS A higher LDL cholesterol level was associated with increased CSMT and CSMV in diabetic patients without DME. Prospective longitudinal studies are warranted to assess whether having both elevated levels of LDL and higher CSMT or CSMV is a risk indicator for subsequent development of DME.

Detection of early visual impairment in patients with epiretinal membrane.

Purpose:  Patients with epiretinal membrane sometimes complain of impaired central visual function, despite good best corrected visual acuity (BCVA), as measured by visual acuity (VA) charts. Here, we evaluate early epiretinal membrane–induced changes in central VA.

Non-responsiveness to intravitreal aflibercept treatment in neovascular age-related macular degeneration: implications of serous pigment epithelial detachment

The prognosis of neovascular age-related macular degeneration (AMD) has been improved by anti-vascular endothelial growth factor treatments, including intravitreal aflibercept (IVA) treatment. However, many patients remain incurable. In this study, we retrospectively evaluated non-responsiveness to IVA monotherapy at 12 months in 133 eyes of 133 AMD patients. Sixty-two patients were initially treatment-naive, and 71 had received other treatments before IVA (the treatment-switched group). Mean best-corrected visual acuity (BCVA) was improved in the treatment-naive group but not in the treatment-switched group, although mean central retinal thickness (CRT) decreased in both groups. The respective percentages of non-responders as determined by worsened BCVA in the treatment-naive and treatment-switched groups were 8.1% and 15.5%, and via fundus findings, they were 12.9% and 8.5%. Multivariate analyses adjusted for age, gender, CRT, and greatest linear dimension showed that serous pigment epithelial detachment (PED) at baseline was associated with non-responsiveness in both groups as determined by BCVA and by fundus findings, and fibrovascular PED measurements indicated no response as determined by fundus findings in the treatment-switched group. The results reported herein may assist the formulation of appropriate treatment protocols for AMD patients.

Serum Vascular Adhesion Protein-1 correlates with vascular endothelial growth factor in patients with type II diabetes☆

AIMS To study serum levels of soluble vascular adhesion protein (sVAP)-1 in type II diabetic patients with retinopathy. METHODS Serum samples were obtained from 53 consecutive patients, including 14 cases with non-angiogenic ocular diseases, i.e., epiretinal membrane (ERM) and idiopathic macular hole (MH), 19 cases with age-related macular degeneration (AMD), and 20 cases with diabetic retinopathy (DR). Protein levels of sVAP-1, intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, and vascular endothelial growth factor (VEGF) were determined by enzyme-linked immunosorbent assay. Enzymatic activity of semicarbazide-sensitive amine oxidase (SSAO) was also measured. RESULTS Serum level of sVAP-1 showed a moderate correlation with SSAO activity in all cases. Patients with DR had higher levels of serum sVAP-1 than subjects with ERM and MH, or those with AMD; however, severity of DR is not related to the serum levels of sVAP-1. Serum sVAP-1 correlated positively with VEGF in patients with DR, but not in those with ERM and MH, or those with AMD. Neither soluble ICAM-1 nor VCAM-1 correlated with VEGF, even in subjects with DR. CONCLUSION The current data demonstrate the elevated serum levels of sVAP-1 and correlation between sVAP-1 and VEGF in patients with type II diabetes.

Early Signs of Exudative Age-Related Macular Degeneration in Asians

Purpose To investigate the relationship between the early signs of age-related macular degeneration (AMD) and the risk of developing exudative AMD (typical AMD or polypoidal choroidal vasculopathy [PCV]) in the fellow eye of Japanese patients with unilateral exudative AMD, focusing particularly on eyes with only pigmentary abnormality. Methods This study is a retrospective observational consecutive case series. We retrospectively reviewed the medical charts of patients who revisited the AMD clinic from 2010 to 2011 and confirmed 129 cases with unilateral exudative AMD at their first visit (baseline). The non-affected eyes at baseline (the second eye) were categorized by the presence of early signs of AMD. The incidence of exudative AMD (typical AMD or PCV) in the fellow eye was confirmed by fluorescein and indocyanine green angiography. Results Of the 129 patients, 14 (10.9%) developed exudative AMD in the fellow eye (median follow-up, 3.2 years; n = 7 typical AMD and n = 7 PCV). Eyes with both pigmentary abnormalities and large drusen were more likely to develop typical AMD (age- and sex-adjusted odds ratio = 9.46, 95% confidence interval = 1.05 to 85.0), whereas pigmentary abnormalities without large drusen were associated with PCV (age- and sex-adjusted odds ratio = 15.9, 95% confidence interval = 1.8 to 140.5). Conclusions There was a difference in the association between early signs of AMD and incident development of either typical AMD or PCV. Further research is warranted to determine whether pigmentary abnormalities alone may be an important risk factor for PCV in Asians.

Wide-Angle Viewing System versus Conventional Indirect Ophthalmoscopy for Scleral Buckling

Wide-angle viewing systems (WAVSs) were originally established for pars plana vitrectomy. However, their application to scleral buckling surgery was recently reported. In this study, we compared the outcomes of scleral buckling using a noncontact WAVS with that of scleral buckling using conventional indirect ophthalmoscopy for rhegmatogenous retinal detachment. The clinical records of 39 eyes (39 patients) with rhegmatogenous retinal detachment primarily treated between November 2012 and June 2014 at the Vitreo-Retina Surgical Division Clinic at the Department of Ophthalmology, Keio University Hospital were retrospectively reviewed. Scleral bucking was performed using WAVS with surgical placement of an endoilluminator in 16 eyes and indirect ophthalmoscopy in 23 eyes. The patients in these groups were consecutive over different intervals. The preoperative demographics, success rate of retinal reattachment, intraoperative findings, and postoperative complications were evaluated. There were no significant differences in pre- or postoperative conditions between groups, and similar surgical outcomes were achieved with the WAVS and conventional procedures. However, compared with the conventional procedure, the WAVS procedure resulted in fewer intraoperative corneal epithelial disorders (p = 0.049) and decreased the surgical duration of segmental buckling (p = 0.02); therefore, it may be suggested as an effective alternative procedure.

Association of macular pigment optical density with serum concentration of oxidized low-density lipoprotein in healthy adults

Purpose: To analyze the association between macular pigment optical density (MPOD), which reflects lutein (L), zeaxanthin (Z), and meso-zeaxanthin (MZ) in the macula, and background characteristics. Methods: Fifty-five healthy adult volunteers were analyzed. Macular pigment optical density was measured using a heterochromatic flicker photometry technique, and serum concentrations of carotenoids and lipoproteins were by high-performance liquid chromatography and enzyme-linked immunosorbent assay, respectively. Dietary intake of nutrient was determined by a validated self-administered questionnaire on ingestion frequency. Results: Macular pigment optical density was positively correlated with serum concentrations of L and Z and dietary L intake and inversely correlated with serum oxidized low-density lipoprotein (LDL). Although MPOD decreased with age (95% confidence interval, −0.011 to −0.002; correlation coefficient, −0.269; P = 0.007), serum L/Z and dietary L intake did not. In contrast, serum oxidized LDL was positively correlated with age (95% confidence interval, 0.69–2.34; correlation coefficient, 0.333; P = 0.0004). After adjusting for age, sex, and oxidized LDL, serum L was positively correlated with MPOD (95% confidence interval, 0.88–1.69; P = 0.000001). After adjusting for age, sex, and serum L, serum oxidized LDL was inversely correlated with MPOD (95% confidence interval, −0.002 to −0.0004; P = 0.006). Conclusion: Macular pigment optical density was inversely correlated with serum oxidized LDL. Further study to know the impact of oxidized LDL on MPOD may be warranted.

Functional Visual Acuity in Age-Related Macular Degeneration.

Purpose We evaluated whether a functional visual acuity (FVA) system can detect subtle changes in central visual acuity that reflect pathological findings associated with age-related macular degeneration (AMD). Methods Twenty-eight patients with unilateral AMD and logMAR monocular best corrected VA better than 0 in both eyes, as measured by conventional chart examination, were analyzed between November 2012 and April 2013. After measuring conventional VA, FVA, and contrast VA with best correction, routine eye examinations including spectral domain–optical coherence tomography were performed. Standard Schirmer test was performed, and corneal and lens densities were measured. Results The FVA score (p < 0.001) and visual maintenance ratio (p < 0.001) measured by the FVA system, contrast VA (p < 0. 01), and conventional VA (p < 0.01) were significantly worse in the AMD-affected eyes than in the fellow eyes. No significant differences were observed in the anterior segment conditions. Forward stepwise regression analysis demonstrated that the length of interdigitation zone disruption, as visualized by optical coherence tomography imaging, correlated with the FVA score (p < 0.01) but not with any other parameters investigated. Conclusions The FVA system detects subtle changes in best corrected VA in AMD-affected eyes and reflects interdigitation zone disruption, an anatomical change in the retina recorded by optical coherence tomography. Further studies are required to understand the value of the FVA system in detecting subtle changes in AMD.

Use of Micronutrient Supplement for Preventing Advanced Age-Related Macular Degeneration in Japan

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