Takashi Koto

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.

Involvement of hyaluronan and its receptor CD44 with choroidal neovascularization

PURPOSE CD44 is a cell-surface adhesion molecule and receptor for hyaluronan (HA), one of the major extracellular matrix components. The purpose of the present study was to clarify a role of HA and CD44 in the development of choroidal neovascularization (CNV). METHODS Laser photocoagulation was used to induce CNV in C57BL/6 mice or CD44-deficient mice. The mRNA expression of CD44 and HA synthase (HAS)-2 in the retinal pigment epithelium (RPE)-choroid complex was evaluated by DNA microarray and real-time RT-PCR analyses 3 days after laser treatment. HA synthesis and CD44 expression were examined by immunohistochemistry 1 week after photocoagulation. Mice with laser-induced CNV were systemically administered the HA synthesis inhibitor 4-methylumbelliferone (MU) or an anti-CD44-neutralizing antibody. The response of CNV was analyzed by volumetric measurements 1 week after photocoagulation. Macrophage infiltration into CNV lesions was evaluated by real-time RT-PCR for F4/80 3 days after laser-induced injury. RESULTS The induction of CNV led to a significant increase in expression of CD44 and HAS2 mRNA. HA and CD44 were immunopositive in the CNV lesions. Compared with vehicle treatment, the systemic application of MU significantly attenuated CNV volume in a dose-dependent fashion, together with macrophage infiltration into the lesions. Consistently, antibody-based blockade of CD44 resulted in a significant reduction of CNV volume, compared with the isotype control. In contrast, genetic ablation of CD44 significantly augmented CNV formation together with HA accumulation and macrophage infiltration, compared with wild-type mice. CONCLUSIONS These results indicate a significant role of HA and its receptor CD44 in the development of CNV.

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.

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.

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.

Inverted Internal Limiting Membrane Flap Technique For Treatment Of Macular Hole Retinal Detachment In Highly Myopic Eyes

Purpose: To compare the efficacy of vitrectomy with inverted internal limiting membrane (ILM) flap to complete removal of the ILM for the treatment of macular hole (MH) retinal detachment in highly myopic eyes. Methods: Pars plana vitrectomy with inverted ILM flap technique (16 eyes; inverted group) or with the complete removal of the ILM (16 eyes; removed group) was performed in patients with high myopia with MH retinal detachment. The rate of retinal reattachment and MH closure, the best-corrected visual acuities, and the integrity of the foveal microstructures in the optical coherence tomographic images were compared. Results: Thirteen eyes (81%) in the inverted group and 15 eyes (93%) in the removed group had retinal reattachment after the initial surgery (P = 0.30). The MH was closed significantly more often in the inverted group (75%) than in the removed group (25%; P = 0.006). The postoperative best-corrected visual acuity was significantly better in the inverted group (P = 0.04). The number of eyes with outer nuclear layer, external limiting membrane, and ellipsoid zone lines at the closed MH was not significantly different in the two groups. Conclusion: The inverted ILM flap technique with the presence of bridging tissue over the MH is effective in closing the MH and improving the postoperative best-corrected visual acuity in eyes with MH retinal detachment by bridging tissue over the MH.

Predisposing factors for intraocular lens dislocation treated by pars plana vitrectomy: Involvement of atopic dermatitis

IOL in the bag is advocated because it is easier tomanipulate and prolapse out of the bag and it ensures greater degrees of entrapment of the anterior capsule behind the IOL optic as a result of its design compared with that of 1-piece IOLs. Studies report a reduced incidence of capsule opacification with the use of CTRs as they help maintain the tautness of the capsular bag, which is important as the optic is placed anteriorly, even though the haptics maintain their position in the bag. Because the haptics remain in the bag, theoretically a modest myopic shift would be induced, varying directly with the power of the IOL. The IOLs implanted in the eyeswere of the samepower calculated for in-thebag placement, and no major refractive surprise occurred that necessitated surgical intervention. The concept of performing primary reverse optic capture is debatable; however, it has been observed that patients who have negative dysphotopsia in 1 eye do not develop it in the other eye when they have primary reverse optic capture. However, negative dysphotopsia symptoms might not be bilateral. Long-term studies with longer follow-upare essential to establish the effectiveness of the procedure.

Association of Maternal Age to Development and Progression of Retinopathy of Prematurity in Infants of Gestational Age under 33 Weeks

Aim. To find predictive and indicative markers of risk for development of retinopathy of prematurity (ROP) and its progression to the stage requiring laser treatment, in premature infants whose gestational age (GA) was under 33 weeks. Methods. We retrospectively reviewed medical records of 197 premature infants born in 2005–2010 whose GA < 33 weeks and underwent eye screening at Keio University Hospital. The association between candidate risk factors and development or progression of ROP was assessed. Results. Among the 182 eligible infants (median GA, 29.1 weeks; median birth weight (BW), 1028 g), 84 (46%) developed any stage of ROP, of which 45 (25%) required laser treatment. Multivariate analysis using a stepwise method showed that GA (P = 0.002; 95% confidence interval (CI), 0.508–0.858), BW (P < 0.001; 95% CI, 0.994–0.998), and lower maternal age (P = 0.032; 95% CI, 0.819–0.991) were the risk factors for ROP development and GA (P < 0.001; 95% CI, 0.387–0.609) and lower maternal age (P = 0.012; 95% CI, 0.795–0.973) were for laser treatment. The odds ratio of requiring laser treatment was 3.3 when the maternal age was <33 years. Conclusion. ROP was more likely to be developed and progressed in infants born from younger mother and low GA.

DURATION OF PRONE POSITIONING AFTER MACULAR HOLE SURGERY DETERMINED BY SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY

Purpose: To compare the closure rate of macular hole closure and duration of the prone positioning after macular hole (MH) surgery with two protocols for halting the prone positioning. Methods: The authors studied 129 eyes of 125 consecutive patients with MH who had undergone vitrectomy. In 60 eyes of 59 patients, the prone positioning was halted after detecting an MH closure in the swept-source optical coherence tomographic images (SS group). In 69 eyes of 66 patients, the prone position was halted by the surgeons decision (conventional group). The MH closure rate and duration of the prone positioning were compared. Results: Clear images of the MH were recorded in the SS group on postoperative Day 1 in 58 eyes (97%). In the SS group, MH closure was detected on postoperative Day 1 in 47 eyes (78%) and Day 2 in 4 eyes (7%). The MH was closed in 58 eyes (97%) in the SS group and 69 eyes (100%) in the conventional group (P = 0.21). None of the eyes had a reopening of the MH. The duration of prone positioning in the SS group was 1.8 ± 2.5 days, which was significantly shorter than that in the conventional group at 8.4 ± 4.2 days (P < 0.0001). Conclusion: The SS-OCT protocol can significantly decrease the duration of the prone positioning without a reopening of the MH.