One-Year Results of a Treat-and-Extend Regimen of Intravitreal Aflibercept for Polypoidal Choroidal Vasculopathy.

INTRODUCTION: To evaluate 1-year outcomes of intravitreal aflibercept (IVA) using a treat-and-extend (TAE) regimen for polypoidal choroidal vasculopathy (PCV) and identify the factors for patients whose treatment intervals could be extended. METHODS: Fifty-one eyes of treatment-naïve PCV patients treated with IVA using a TAE regimen for at least 1 year were examined retrospectively. All patients received at least three IVA injections every 5 weeks, and the intervals were then extended by 2-week adjustments up to 13 weeks. When retinal exudation recurred, the patient was treated with the same regimen, but with a shortened interval of 5 weeks. The main outcome measures were changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) as well as the treatment interval at 1 year. RESULTS: The mean logarithm of the minimum angle of resolution BCVA improved from 0.24 ± 0.32 at baseline to 0.18 ± 0.31 at 12 months (p = 0.048). The mean CRT decreased from 350.3 ± 147.7 µm at baseline to 215.3 ± 75.0 µm at 4 months (p < 0.001), after which it was maintained at this level. At 12 months, the administration interval was 5 weeks in eight eyes (15.7%), 7 weeks in six eyes (11.8%), 9 weeks in two eyes (3.9%), 11 weeks in four eyes (7.8%), and 13 weeks in 31 eyes (60.8%). Female sex, a thinner CRT at 6 months, and absence of polypoidal lesions at 12 months were significant factors related to patients whose treatment intervals could be extended without recurrence to 13 weeks. CONCLUSION: IVA using a TAE regimen improved visual and anatomical outcomes in eyes with PCV at 1 year using a protocol to adjust the injection intervals specifically for each patient so as to obtain no retinal exudation.

EFFICACY AND SAFETY OUTCOMES OF INTRAVITREAL AFLIBERCEPT FOCUSING ON PATIENTS WITH DIABETIC MACULAR EDEMA FROM JAPAN.

PURPOSE: To evaluate the efficacy and safety of intravitreal aflibercept injection (IAI) in Japanese patients with diabetic macular edema (DME). METHODS: VIVID-DME was a Phase 3 study comprising patients with DME randomized 1:1:1 to IAI 2 mg every 4 weeks (2q4), IAI 2 mg every 4 weeks until Week 16 then 8-week dosing (2q8), and laser. A total of 403 patients (76 Japanese) were included in this study. VIVID-Japan (72; all Japanese patients) was a nonrandomized, open-label study comprising Japanese patients with DME receiving IAI 2q4 until Week 16, then 2q8. Primary efficacy endpoint (Week 52) of VIVID-DME was mean change from baseline in best-corrected visual acuity; VIVID-Japan evaluated safety and tolerability. RESULTS: Mean change in best-corrected visual acuity (letters) for 2q4, 2q8, and laser groups was +10.6, +10.9, and +1.2 and +9.8, +9.5, and +1.1 in the non-Japanese and Japanese populations of VIVID-DME, respectively. In VIVID-Japan, it was +9.3 for IAI 2q8. Intravitreal aflibercept injection also provided consistently greater benefits for anatomical outcomes versus laser. Adverse events were consistent with the known safety profile of IAI. CONCLUSION: In Japanese patients with DME, IAI treatment was superior to laser for visual and anatomical outcomes and resulted in efficacy and safety outcomes similar to those in a non-Japanese patient population.

Retinal sensitivity after selective retina therapy (SRT) on patients with central serous chorioretinopathy.

PURPOSE: To assess retinal sensitivity after selective retina therapy (SRT) in patients with central serous chorioretinopathy (CSCR). METHODS: Seventeen eyes of 17 patients with CSCR lasting longer than 3 months were treated with SRT (wavelength 527 nm Nd: YLF laser, 50-150 µJ/pulse, spot diameter 200 µm). Measurement of best-corrected visual acuity (BCVA), optical coherence tomography, fluorescence angiography, and microperimetry (MAIA™) were conducted before, and 1 and 3 months after treatment. Microperimetry was performed in the central 10° of the macula, and at the test spots applied near the vascular arcade for energy titration. In addition to the treatment effect, all test irradiation spots were thoroughly analyzed with regard to their sensitivity changes. RESULTS: The mean logMAR BCVA had improved from 0.06 to 0.02 after 1 month (p = 0.11) and to 0.03 after 3 months (p = 0.003). Eleven out of 17 eyes (64.7%) showed complete resolution of subretinal fluid after 3 months. Retinal sensitivity in the central 10° increased after 1 month (median: 25.9 dB) and 3 months (26.6 dB) as compared with that before treatment (23.0 dB) (p < 0.001). Analysis of the test spots revealed a slight decrease in retinal sensitivity after 1 month (ΔdB = -0.5 ± 2.1, p = 0.006), while there was no significant difference from baseline after 3 months (ΔdB = -0.3 ± 2.2, p = 0.09). No correlation was found between laser energy and the change in focal retinal sensitivity. CONCLUSIONS: Results suggest that SRT is a safe and effective treatment for persistent CSCR and does not leave permanent scotoma regardless of irradiation energy in the therapeutic range.

Evidence of Effect of Day Length Factor on Infantile Refractive Development: Multiple Regression Analysis-based Examination of Refractive Components of Cataracts.

Purpose: As the relationships between refraction and birth month suggest that day length factors affect the infantile refractive development, we aimed to prove the effect of day length factors by examining its evidence even among the elderly. Methods: We studied 1622 patients with cataracts (740 men and 882 women) who had preparatory measurements for corneal radius, axial lengths, and refractions for intraocular lens implantation. The day lengths for which each subject was exposed to from the first to eleventh month since birth were represented by variables DL1 to DL11. Similarly, absolute deviations from the yearly average of day lengths were represented by DDL1 to DDL11. We performed multiple regression analysis by substituting DL or DDL as explanatory variables for corneal radius, axial length, or refraction. Results: DLs were not relevant variables in elucidating corneal radius, axial length, and refraction. In contrast, DDLs were relevant variables in elucidating corneal radius (p<0.05). This association weakened for refraction and was not pertinent for axial length. Conclusion: Infantile refractive development is affected by the deviation in day length rather than the day length itself, evidence for which can still be observed among the elderly.

Optic Neuritis Associated with Myelodysplastic Syndrome Accompanied by Eosinophilic Crisis.

Myelodysplastic syndrome (MDS) was diagnosed in a 64-year-old man. Three months later, he presented with right-sided visual loss. A diagnosis of optic neuritis caused by both ischemic and non-ischemic changes was established. Concurrently, prominent eosinophilia was seen in both the peripheral blood and bone marrow. A partial improvement of visual loss was obtained concomitant with a rapid decrease of the eosinophils after treatment with corticosteroids. Optic neuritis related to MDS is a rare condition and its etiology has not yet been identified. We herein report a case of optic neuritis associated with MDS and accompanied by an eosinophilic crisis.

Protective effect of a laser-induced sub-lethal temperature rise on RPE cells from oxidative stress.

Recently introduced new technologies that enable temperature-controlled laser irradiation on the RPE allowed us to investigate temperature-resolved RPE cell responses. In this study we aimed primarily to establish an experimental setup that can realize laser irradiation on RPE cell culture with the similar temperature distribution as in the clinical application, with a precise time/temperature history. With this setup, we conducted investigations to elucidate the temperature-dependent RPE cell biochemical responses and the effect of transient hyperthermia on the responses of RPE cells to the secondary-exposed oxidative stress. Porcine RPE cells cultivated in a culture dish (inner diameter = 30 mm) with culture medium were used, on which laser radiation (λ = 1940 nm, spot diameter = 30 mm) over 10 s was applied as a heat source. The irradiation provides a radially decreasing temperature profile which is close to a Gaussian shape with the highest temperature in the center. Power setting for irradiation was determined such that the peak temperature (Tmax) in the center of the laser spot at the cells reaches from 40 °C to 58 °C (40, 43, 46, 50, 58 °C). Cell viability was investigated with ethidium homodimer III staining at the time points of 3 and 24 h following laser irradiation. Twenty four hours after laser irradiation the cells were exposed to hydrogen peroxide (H2O2) for 5 h, followed by the measurement of intracellular glutathione, intracellular 4-hydroxynonenal (HNE) protein adducts, and secreted vascular endothelial growth factor (VEGF). The mean temperature threshold for RPE cell death after 3 h was found to be around 52 °C, and for 24 h around 50 °C with the current irradiation setting. A sub-lethal preconditioning on Tmax = 43 °C significantly induced the reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio, and decreased H2O2-induced increase of intracellular 4-HNE protein adducts. Although sub-lethal hyperthermia (Tmax = 40 °C, 43 °C, and 46 °C) caused a slight increase of VEGF secretion in 6 h directly following irradiation, secondary exposed H2O2-induced VEGF secretion was significantly reduced in the sub-lethally preheated groups, where the largest effect was seen following the irradiation with Tmax = 43 °C. In summary, the current results suggest that sub-lethal thermal laser irradiation on the RPE at Tmax = 43 °C for 10 s enhances cell defense system against oxidative stress, with increasing the GSH/GSSG ratio. Together with the results that the decreased amount of H2O2-induced 4-HNE in sub-lethally preheated RPE cells was accompanied by the lower secretion of VEGF, it is also strongly suggested that the sub-lethal hyperthermia may modify RPE cell functionality to protect RPE cells from oxidative stress and associated functional decrease, which are considered to play a significant role in the pathogenesis of age-related macular degeneration and other chorioretinal degenerative diseases.

Subretinal fluid drainage via original retinal breaks for rhegmatogenous retinal detachment.

OBJECTIVE: To evaluate the outcome of vitrectomy using only original retinal breaks for subretinal fluid (SRF) drainage during the repair of primary rhegmatogenous retinal detachment (RRD). DESIGN: A retrospective consecutive interventional case series. PARTICIPANTS: A consecutive series of 112 eyes of 112 patients. METHODS: Patients underwent 23-gauge vitrectomy without the use of posterior retinotomy and perfluorocarbon liquids for uncomplicated primary RRD at Osaka City University Hospital between September 2007 and March 2011. Exclusion criteria included eyes with giant retinal tears, grade C2 or worse proliferative vitreoretinopathy (PVR), ocular trauma, and the presence of other vitreoretinal diseases. RESULTS: Single-operation success rate was 92.9%, whereas final anatomical success rate was 100%. Median visual acuity improved significantly from the preoperative logMAR of 0.51 ± 0.78 to the postoperative logMAR of 0.03 ± 0.26 (p < 0.01). No significant differences were observed for the single-operation success rate between the 62 eyes (95.2%) in which some SRF remained at the end of the operation and the rest of the 50 eyes (90.0%, p = 1.000) in which the SRF had been completely aspirated. Complications included transient intraocular pressure rise (12 eyes, 10.7%), epiretinal membrane (5 eyes, 4.5%), and PVR (1 eye, 0.9%). Ocular hypotony and endophthalmitis were not observed. CONCLUSIONS: Uncomplicated primary RRD can be successfully repaired by performing vitrectomy using only the original retinal breaks for SRF drainage. In addition, successful outcomes are not dependent on achieving complete reattachment of the retina throughout the fundus.

[Relationship between birth month and corneal radius or axial length].

PURPOSE: Hyperopia prevalence is higher in children born in the autumn. This study attempted to detect whether corneal curvature or axial length are related to this phenomenon. METHODS: Using data from a total of 4056 cataract patients aged 40 and over from three medical facilities, corneal radius and axial length, measured to determine the intraocular lens power needed for cataract surgery, were reviewed. Mean corneal radius and mean axial length were calculated for each birth month. The means were then graphically analyzed to determine the relationship of corneal radius or axial length with birth month. RESULTS: No correlation was noted between axial length and birth month. However, a correlation between corneal radius and birth month was observed in each of the three facilities. Specifically, subjects born from October through December tended to have larger corneal radii. Numerically, the corneal radius showed a statistical relationship in terms of birth month (p < 0.001, ANOVA), while the axial length showed no relationship (p = 0.907, ANOVA). CONCLUSION: A statistically meaningful relationship between corneal curvature and birth month was detected. Corneal development might be affected by seasonal daylight variations in infancy, thus contributing to the occurrence of hyperopia.

Two-year results of reduced-fluence photodynamic therapy combined with intravitreal ranibizumab for typical age-related macular degeneration and polypoidal choroidal vasculopathy.

PURPOSE: To report the 2-year results of reduced-fluence photodynamic therapy (RF-PDT) combined with intravitreal ranibizumab (IVR) for typical age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV). METHODS: Twenty-four previously untreated eyes of 23 AMD patients with decimal best-corrected visual acuity (BCVA) of less than 0.7 received the combined therapy, followed by retreatments as needed over the subsequent 2 years. When the BCVA was better than or equal to 0.7, only 3 monthly IVR injections were performed during the retreatment. RESULTS: The BCVAs were maintained in 7 of 10 typical AMD eyes and in 13 of 14 PCV eyes at month 24. The mean BCVA improved in the PCV group (P < 0.05) but not in the typical AMD group. The central foveal thickness decreased in both groups (P < 0.01, P < 0.001). The mean numbers of the total PDT and IVR injections were 1.8 and 7.2 in the typical AMD group and 1.8 and 6.4 in the PCV group. CONCLUSION: After RF-PDT combined therapy with administration of retreatments as needed that consisted of either 3 IVR injections alone or combined therapy, the BCVA was maintained in typical AMD and improved in PCV during a 2-year follow-up period.

A case of persistent hypotony following 23-gauge vitrectomy.

We report here a case in which ciliary detachment related to the preparation of a scleral wound was suspected as the cause of persistent hypotony following 23-gauge vitrectomy for proliferative diabetic retinopathy. Ultrasound biomicroscopy (UBM) was performed following injection of a viscoelastic substance into the anterior chamber to carefully investigate the treatment and cause of persistent hypotony. Deepening the anterior chamber by means of the viscoelastic substance enabled UBM identification of ciliary detachment that had not been detected in the shallow anterior chamber. The extent of ciliary detachment was approximately 8 degrees; however, the detachment could not be seen on gonioscopy. UBM showed no continuity between the anterior chamber and choroid, with findings suggesting that the two structures had been split by posterior traction. The ciliary detachment site was the same site at which a three-port system had been prepared. One advantage of a 23-gauge system is that few complications are associated with the insertion and retraction of instruments. However, the difference in level between the cannula and trocar may result in ciliary detachment even if no resistance is felt when the trocar is inserted.

Progression of cataracts following photodynamic therapy combined with intravitreous triamcinolone injection in cases of age-related macular degeneration.

BACKGROUND: To present long-term data on the progression of cataracts following photodynamic therapy (PDT) combined with 4 mg intravitreal triamcinolone acetonide (IVTA) for age-related macular degeneration (AMD). METHODS: Fifty-seven phakic eyes of 56 patients underwent the treatment between October 2004 and November 2006. The follow-up period ranged from 12 to 38 months with 3 months interval of observation and repeated treatment at recurrence. RESULTS: Cataract progression was noted in 40 eyes 5-21 months after treatment, consisting of 4 eyes between 3 and < 6 months after treatment, 22 eyes between 6 and < 12 months, 8 eyes between 12 and < 18 months, and 6 eyes between 18 and < 24 months. The percentage of the eyes with cataract progression began to decrease 5 months after treatment and, occurred most frequently during the period from 6 months to 12 months after treatment. There was no significant difference in age, follow-up period, or the frequency of the treatment between the cataract progression group and the non progression group. Twenty four eyes underwent surgery 10-31 months after treatment, showing significant improvement in visual acuity. CONCLUSIONS: This study showed high incidence of cataract during a long-term follow-up after PDT combined with IVTA and significant reduction of visual acuity due to cataract.

Effect of travoprost on 24-hour intraocular pressure in normal tension glaucoma.

PURPOSE: The effect of travoprost 0.004% on 24-hour intraocular pressure (IOP) was examined in patients with normal tension glaucoma (NTG). SUBJECTS AND METHODS: This study included 17 patients with newly diagnosed unilateral NTG. IOP was measured at three-hour intervals over 24 hours by Goldman applanation tonometer in patients taking topical travoprost 0.004% and was compared retrospectively with 24-hour IOP data in untreated eyes. RESULTS: IOP values were significantly reduced at individual time points after treatment (P < 0.01). Mean 24-hour IOP, maximum 24-hour IOP, minimum 24-hour IOP, and 24-hour IOP fluctuations at baseline (mean +/- SD) were 12.9 +/- 2.2 mmHg, 15.4 +/- 2.7 mmHg, 10.5 +/- 2.2 mmHg, and 4.9 +/- 1.2 mmHg, respectively, and were significantly reduced to 10.3 +/- 2.0 mmHg, 12.4 +/- 2.5 mmHg, 8.5 +/- 1.9 mmHg (all P < 0.001), and 3.9 +/- 1.5 mmHg (P < 0.05), respectively, after treatment. The rate of IOP reduction greater than 20% was 58.8% (10 eyes) for maximum 24-hour IOP and 53.0% (nine eyes) for mean 24-hour IOP. CONCLUSION: Travoprost reduced IOP throughout the 24-hour study period, with over half of the eyes examined showing IOP reduction exceeding 20%.

Surgical procedure for correcting globe dislocation in highly myopic strabismus.

PURPOSE: To design a surgical procedure for correcting globe dislocation in strabismus in high myopia (highly myopic strabismus). DESIGN: Prospective, interventional case series. METHODS: We examined 36 eyes of 21 patients with highly myopic strabismus and 27 eyes of 27 healthy volunteers as controls at Osaka City General Hospital between 2000 and 2006. Anatomic relationships between the muscle cone and globe were analyzed using magnetic resonance imaging. Ranges of globe movement and angles of ocular deviation were measured quantitatively as angles of maximum abduction and sursumduction and angles of ocular deviation, respectively, using the Goldmann perimeter and alternate prism cover tests. A surgical procedure involving muscle union of the superior rectus and lateral rectus muscles was performed in 23 eyes of 14 patients to restore the dislocated globe back to the muscle cone. RESULTS: After surgery, the angle of dislocation of the globe, defined as the angle formed by a line connecting the area centroid of the superior rectus muscle and the globe and a line connecting area centroid of the lateral rectus muscle and globe against the supertemporal wall of the orbit, was significantly decreased (P < .001), and angles of maximum abduction and sursumduction and the angle of ocular deviation improved significantly (P < .001). CONCLUSIONS: This surgical procedure to restore the dislocated globe back into the muscle cone by uniting muscle bellies of the superior rectus and lateral rectus muscles is effective for highly myopic strabismus.

Comparison of fundus autofluorescence of age-related macular degeneration between a fundus camera and a confocal scanning laser ophthalmoscope.

BACKGROUND: Fundus autofluorescence (FAF) has been examined using two devices, which were the conventional confocal scanning laser ophthalmoscope and the improved fundus camera. We examined the comparison of fundus autofluorescence (FAF) from a fundus camera (FC) and a confocal scanning laser ophthalmoscope (cSLO) in patients with age-related macular degeneration (AMD). METHODS: Two hundreds ninety-two eyes of 202 AMD patients were examined for FAF. FAF images were captured with a FC and a cSLO system, and were compared for serous retinal detachment lesion (SRD), subretinal fibrovascular tissue lesion (FVM), pigment epithelial detachment lesion (PED), geographic atrophy lesion (GA), macular aria, and choroidal vessels. RESULTS: Clear FAF images were obtained using both instruments in 212 eyes of 147 patients (72.6%). Correlations of FAF findings between the 2 systems existed for SRD, FVM, and GA, but not for PED. The FAF accordance rates between the 2 systems were 61.1% at SRD, 68.4% at FVM, 35% at PED, and 83.4% at GA; and GA had a significantly higher accordance ratio than other lesions. FAF images with the cSLO tended to hypoautofluorescence compared to those with a FC, except at GA. Maculas without any abnormal lesion of 41 eyes apparently hypoautofluorescence more with the cSLO than the FC. Some choroidal vessels autofluoresced in 21 eyes only with the FC. CONCLUSIONS: FAF examination differed between the two systems. To compare two FAF images may be useful for identifying pathogonomonic fundus changes undetectable by only either FAF examination.

Medial orbitotomy without opening the ethmoid sinus enables wide exposure and safe removal of an orbital tumour located posterosuperomedially.

Tumours in the posterosuperomedial orbital space are hard to remove because of their site. However, medial orbitotomy without opening the ethmoid sinus produces a wide enough view and a direct route without complications. Posterosuperomedial orbital tumours can therefore be safely, accurately, and easily removed.

The rate of symptomatic improvement of congenital nasolacrimal duct obstruction in Japanese infants treated with conservative management during the 1st year of age.

This study aimed to examine the rate of symptomatic improvement of congenital nasolacrimal duct obstruction (CNLDO) in Japanese infants treated with conservative management within the 1st year of age. Thirty-five lacrimal ducts in 27 patients diagnosed with CNLDO were included in the study. During the observational period, lacrimal ducts were massaged. As well, antibiotic eye drops, to be administered 4 times a day, were sometimes prescribed for obvious conjunctivitis. Two lacrimal ducts in 2 patients were probed before the 1st year of age because of dacryocystitis or severe blepharitis; these patients were included in the unimproved group. Twenty-nine lacrimal ducts in 21 patients resolved during the period (82.9%); with 16 lacrimal ducts resolving before six months of age. Therefore, a comparatively high percentage of resolution for CNLDO (82.9%) following conservative management was shown before the 1st year of age in Japanese infants.

Digital image analysis of choroidal hypoperfusion in indocyanine green angiography using a choroid to disc gray-scale ratio.

PURPOSE: To investigate hypoperfusion of the choroidal circulation in the macula, the brightness of the diffuse fluorescence of indocyanine green (ICG) angiogram (IA) was measured and the ratio of brightness of the macula to that of the disc was used for comparison of choroidal perfusion between different angiograms. METHODS: Ten eyes of 10 young volunteers under 30 years of age (17-28 years old, average 24.7 years old), 10 eyes of 10 old volunteers over 60 years old (60-78 years old, average 66.7 years old) and 5 eyes of 5 patients with age-related macular degeneration (AMD) were examined by IA. The angiograms at 4 and 16 seconds after dye filling were used to measure the brightness of diffuse fluorescence at the macula and the disc on ICG angiograms with a 256-grade gray scale using the Topcon IMAGEnet computer system. The ratio (ch/d ratio) of the averaged brightness of the macula to that of the disc was calculated for each angiogram. RESULTS: The ch/d ratios of the angiograms 4 seconds after dye filling were 1.41 in the young volunteers, 1.23 in the old volunteers and 0.52 in the AMD patients. The ch/d ratios of the angiograms 16 seconds after dye filling were 0.92 in the young volunteers, 1.02 in the old volunteers and 0.80 in AMD. There were significant differences in the ch/d ratios among the 3 groups 4 seconds after dye filling (p=0.007, Kruskal-Wallis H test,) but there were no significant differences 16 seconds after dye filling (p=0.310). CONCLUSION: The ch/d ratio is an adjunctive method for detecting choroidal hypoperfusion in IA, and may be helpful for objective evaluation of the choroidal circulation in chorioretinal diseases.

Iris prolapse after non-penetrating trabeculectomy with sinusotomy and mitomycin C.

Non-penetrating trabeculectomy (NPT) is effective in preventing numerous postoperative complications encountered with trabeculectomy. Recently, NPT has been modified to further reduce intraocular pressure (IOP) by combining other techniques. However, these modified NPT methods would make the globe even weaker than NPT alone. Here, we report a case of iris prolapse caused by blunt ocular trauma after NPT with sinusotomy and mitomycin C treatment. A 68-year-old man, who underwent NPT with sinusotomy and mitomycin C treatment, suffered from blunt ocular trauma to his left eye 28 days after surgery. The iris prolapsed from the sinusotomy site. Iridectomy, scleral suturing, and pars plana vitrectomy were performed. The bleb was absent post-re-operatively. Iris prolapse occurs uncommonly following simple NPT. However, additional sinusotomy and mitomycin C treatment render the globe weaker, and iris prolapse might occur. Iris prolapse increases risks in developing secondary infections and a loss of the filtration bleb. Thus, precautions are needed postoperatively.