Azusa Fujikawa

Antibodies to myelin oligodendrocyte glycoprotein in idiopathic optic neuritis

Objectives To investigate the differences of clinical features, cerebrospinal fluid (CSF), MRI findings and response to steroid therapies between patients with optic neuritis (ON) who have myelin oligodendrocyte glycoprotein (MOG) antibodies and those who have seronegative ON. Setting We recruited participants in the department of neurology and ophthalmology in our hospital in Japan. Methods We retrospectively evaluated the clinical features and response to steroid therapies of patients with ON. Sera from patients were tested for antibodies to MOG and aquaporin-4 (AQP4) with a cell-based assay. Participants Between April 2009 and March 2014, we enrolled serial 57 patients with ON (27 males, 30 females; age range 16–84 years) who ophthalmologists had diagnosed as having or suspected to have ON with acute visual impairment and declined critical flicker frequency, abnormal findings of brain MRI, optical coherence tomography and fluorescein fundus angiography at their onset or recurrence. We excluded those patients who fulfilled the diagnostic criteria of neuromyelitis optica (NMO)/NMO spectrum disorders (NMOSD), MS McDonalds criteria, and so on. Finally we defined 29 patients with idiopathic ON (14 males, 15 females, age range 16–84 years). Results 27.6% (8/29) were positive for MOG antibodies and 3.4% (1/29) were positive for AQP4. Among the eight patients with MOG antibodies, five had optic pain (p=0.001) and three had prodromal infection (p=0.179). Three of the eight MOG-positive patients showed significantly high CSF levels of myelin basic protein (p=0.021) and none were positive for oligoclonal band in CSF. On MRIs, seven MOG-positive patients showed high signal intensity on optic nerve, three had a cerebral lesion and one had a spinal cord lesion. Seven of the eight MOG-positive patients had a good response to steroid therapy. Conclusions Although not proving primary pathogenicity of anti-MOG antibodies, the present results indicate that the measurement of MOG antibodies is useful in diagnosing and treating ON.

RETINAL BLOOD FLOW CORRELATES TO AQUEOUS VASCULAR ENDOTHELIAL GROWTH FACTOR IN CENTRAL RETINAL VEIN OCCLUSION.

Purpose: As laser speckle flowgraphy can measure blood flow distribution in the ocular fundus, the authors analyzed the relationship between retinal blood flow and aqueous vascular endothelial growth factor (VEGF) concentration in central retinal vein occlusion. Methods: This prospective observational study examined 45 eyes of 45 patients with central retinal vein occlusion before treatment. Blood flow in large vessels around and at the optic disk, aqueous VEGF concentration, and arteriovenous passage time were examined. Blood flow was evaluated as mean blur rate by laser speckle flowgraphy. Results: Fluorescein angiography found 20 ischemic and 25 nonischemic type eyes. Aqueous VEGF concentration in the ischemic type was significantly higher than that in the nonischemic type (P = 0.01). Arteriovenous passage time was significantly correlated to the logarithm of the aqueous VEGF concentration (P = 0.0001). Mean blur rate of the affected eye/mean blur rate of the unaffected eye of the ischemic type was significantly lower than the nonischemic type (P = 0.039). Additionally, mean blur rate was significantly correlated both to the logarithm of the aqueous VEGF concentration (P < 0.0001) and to the arteriovenous passage time (P = 0.0001). Conclusion: Laser speckle flowgraphy may be useful for predicting aqueous VEGF concentration and severity of central retinal vein occlusion.

Spontaneous dislocation of in-the-bag intraocular lens primarily in cases with prior vitrectomy:

Purpose To report cases of late onset spontaneous in-the-bag dislocation of the intraocular lens (IOL) and to compare these results with past reports. Methods We retrospectively studied 21 eyes of 18 patients with dislocation of the entire capsular bag containing the IOL. Gender, age, interval between original surgery and IOL dislocation, and the predisposing factors were examined. Cases occurring after trauma were excluded. Results The mean ± SD age of the 12 men (57.1%) and 9 women included in the study was 67.8±8.6 years at the time of the IOL removal procedure. The interval between the original surgery and the IOL dislocation was 7.9±8.6. Associated clinical conditions included vitrectomy in 8 eyes (40.0%) of 7 patients, high myopia in 3 eyes (14%) of 2 patients, uveitis in 2 eyes (9.5%) of 2 patients, retinitis pigmentosa in 2 eyes (9.5%) of 1 patient, and pseudoexfoliation in 1 eye (4.8%) of 1 patient. There was no identifiable associated condition in 2 eyes (9.5%) of 2 patients, who were comparatively younger than the other cases. This result differs from previously published reports that have found a higher frequency of pseudoexfoliation and lower frequency of prior vitrectomy. Conclusions In-the-bag IOL dislocation was frequently associated with prior vitrectomy and sometimes occurred without specific conditions.

Systemic factors influence the prognosis of diabetic macular edema after pars plana vitrectomy with internal limiting membrane peeling.

Background: To evaluate the prognostic factors for the best-corrected visual acuity (BCVA) and foveal average retinal thickness after vitrectomy with internal limiting membrane (ILM) peeling for diabetic macular edema. Design: Retrospective, single-center study. Participants: This study involved 31 eyes of 27 patients who had undergone vitrectomy with ILM peeling between January 2005 and March 2008. Methods: Relationships between preoperative systemic or ocular factors and BCVA or foveal average retinal thickness before and 6 months after the operation were evaluated. Main Outcome Measures: BCVA and foveal average retinal thickness before and 6 months after the operation. Results: The mean logarithm of the minimum angle of resolution improved from 0.84 ± 0.64 (mean ± standard deviation) preoperatively to 0.64 ± 0.38 six months postoperatively (p = 0.393). Foveal average retinal thickness significantly improved from 473 ± 146 µm preoperatively to 318 ± 108 µm 6 months after the operation (p < 0.0001). Preoperative foveal average retinal thickness was significantly thicker with cardiovascular disease or cerebral infarction (p = 0.0019) or cystoid macular edema (p = 0.0028), while preoperative BCVA was significantly lower when an epiretinal membrane (p = 0.042) was present. Foveal average retinal thickness at the 6-month follow-up was significantly thicker when patients had a higher body mass index (p = 0.0088), were not on dialysis (p = 0.012), or did not have proliferative diabetic retinopathy (p = 0.013). BCVA at the 6-month follow-up was significantly lower in the group with no history of diabetes treatment until diabetic retinopathy was found (p = 0.023) and in patients with a higher preoperative glycosylated hemoglobin (p = 0.033). Conclusions: Preoperatively, BCVA and foveal average retinal thickness were primarily associated with ocular factors, while they were strongly associated with systemic factors, postoperatively. Ocular factor improvements may be related to the surgical procedure.

Imaging of laser-photocoagulated diabetic microaneurysm with spectral domain optical coherence tomography.

Purpose: To analyze the morphology of microaneurysms before and after direct photocoagulation using spectral domain optical coherence tomography. Methods: In 13 eyes of diabetic patients who underwent focal photocoagulation for clinically significant macular edema, microaneurysms were evaluated before, immediately after, 1 month after, and 2 months after photocoagulation with spectral domain optical coherence tomography. The microaneurysms were also evaluated by fluorescein angiography and color fundus photography. The patients underwent focal photocoagulation for microaneurysm. Results: The microaneurysms before photocoagulation in spectral domain optical coherence tomography were observed as circular or elliptical structures with hyperreflective foci within vessel walls. Immediately after photocoagulation, the microaneurysms were changed to indistinct lesions with hyperreflectivity around the microaneurysms. Acoustic shadows developed on the choroidal side of the microaneurysms. If photocoagulation for microaneurysms was appropriately done, retinal changes were limited to within the inner retina around the microaneurysms and no changes were observed in retinal pigment epithelium. Within 2 months after photocoagulation, the microaneurysms changed into fine scars and the retinal structure normalized. Average retinal thickness of the fovea was 432 ± 70 &mgr;m before the procedure but reduced to 373 ± 84 &mgr;m at 2 months post surgery. Conclusion: Focal photocoagulation may be a less invasive method for treating microaneurysms, and spectral domain optical coherence tomography is useful for evaluating the efficacy of photocoagulation.

Retinal blood flow levels measured by laser speckle flowgraphy in patients who received intravitreal bevacizumab injection for macular edema secondary to central retinal vein occlusion.

PURPOSE To report retinal blood flow levels measured by Laser speckle flowgraphy in three patients after they received an intravitreal bevacizumab injection (IVB) for macular edema secondary to central retinal vein occlusion (CRVO). METHODS Three patients (3 eyes) being treated with IVB (1.25 mg/0.05 mL) for secondary macular edema of CRVO were examined. Laser speckle flowgraphy analyses of the blood flow were based on the examinations of mean blur rate (MBR) at the major vessels of the optic disk. Central retinal thickness (CRT) was measured by optical coherence tomography using Macular Cube 512 × 128 scanning protocol. RESULTS After the first IVB, Case 1 exhibited an increase in MBR and decrease in CRT. After 4 months, an additional injection was required because of a subsequent MBR decrease and CRT increase, which led to an increase in MBR and decrease in CRT similar to that observed after the first treatment. Subsequently, blood flow has continued to improve without additional IVB. Macular edema recurrence in Case 2 led to 3 further IVBs over a 6-month period. Although increases in MBR and decreases in CRT were noted, MBR values tended to decline after each IVB. In Case 3, macular edema recurrence led to 5 additional IVBs being carried out within a 1-year period. Continuous MBR increases and CRT decreases were observed in the patient after each IVB. By measuring MBR using laser speckle flowgraphy, we may predict the prognosis of CRVO. CONCLUSION Mean blur rate increases after IVB were confirmed by laser speckle flowgraphy in three patients. Even though CRVO pathology backgrounds can vary, laser speckle flowgraphy may be useful in both determining the CRVO prognosis and in evaluating treatment efficacy.

Acute corneal toxicity of latanoprost with different preservatives

Abstract Purpose: To investigate the corneal toxicity of Xalatan and three latanoprost generics using transepithelial electrical resistance (TER) and scanning electron microscopy (SEM). Methods: Corneal TER changes after a 60-s exposure to Xalatan (latanoprost 0.005% preserved with 0.02% BAC), and latanoprost generics (Latanoprost PF BAC free, Latanoprost Nitten SB containing sodium benzoate and Latanoprost Towa containing 0.01% BAC with sodium chloride polysorbate 80 as additive) were measured in living rabbits. Corneal damage was also examined by SEM. Hank’s balanced salt solution (HBSS) was used as a control. Results: There was a significant decrease in the corneal TER after exposure of the cornea to Xalatan (p < 0.01) and all latanoprost generics (p < 0.01: Latanoprost PF, p < 0.05: Latanoprost Nitten SB, Latanoprost Towa) as compared to HBSS. All latanoprost generics showed less TER decrease in the corneal TER as compared to Xalatan (p < 0.01). SEM revealed that superficial cells of Xalatan-treated corneas were damaged and exhibited degenerated microvilli. Conversely, the superficial cells of corneas exposed to HBSS or all latanoprost generics appeared normal and had normal microvilli under SEM examinations. Conclusion: The corneal toxicity of Xalatan is greater than that of latanoprost generics. Xalatan contains 0.02% BAC, which may be responsible for the corneal toxicity.

Retro-mode imaging of fibrovascular membrane in proliferative diabetic retinopathy after intravitreal bevacizumab injection

The F10 is a new commercially available scanning laser confocal ophthalmoscope (SLO) that can perform multiple functions. We determined the usefulness of noninvasive evaluation of proliferative diabetic retinopathy (PDR) pathologies before and after intravitreal injection of bevacizumab (IVB) using the new indirect viewing system of the retro-mode function of the F10 SLO, and compared the images histologically with surgically excised fibrovascular membrane from two cases. In PDR, neovascular vessels in fibrovascular membrane were clearly seen with the retro-mode, even after IVB and without blood flow. The F10 SLO may be useful in evaluating neovascular vessels in fibrovascular membrane in PDR and for determining the precise retinal changes in diabetic retinopathy.

Systemic Factors Influence the Prognosis of Diabetic Macular Edema after Pars Plana Vitrectomy with Internal Limiting Membrane Peeling

Abstract Purpose/Aims: To evaluate the prognostic factors for the best corrected visual acuity (BCVA) and central subfield macular thickness (CSMT) after vitrectomy with internal limiting membrane (ILM) peeling for diabetic macular edema. Materials and Methods: A total of 44 eyes of 35 patients who had undergone vitrectomy with ILM peeling between March 2008 and September 2009 were examined. The relationships between preoperative systemic or ocular factors and BCVA or CSMT were evaluated before and at 6 months after the surgical procedure. Results: Mean logarithm of the minimum angle of resolution improved from 0.74 ± 0.35 (mean ± SD) preoperatively to 0.55 ± 0.4 at 6 months postoperatively (p = 0.001). There was a significant improvement of the CSMT from 482 ± 116 μm before the operation to 355 ± 126 μm 6 months after the operation (p < 0.0001). The preoperative CSMT was significantly thicker with ischemic disease (p = 0.0016). Preoperative BCVA was significantly lower when subfoveal hard exudate was present (p = 0.0005). At the 6-month follow-up, CSMT was significantly thicker when there was a higher glycosylated hemoglobin (p = 0.008). BCVA at the 6-month follow-up was significantly lower in the group without any diabetes treatment history (p = 0.0075) prior to the diagnosis of diabetic retinopathy. Conclusions: While BCVA and CSMT were associated with ocular factors before surgery, they were associated with glycemic control postoperatively. Glycemic control may be important for retinal thickness after ocular surgery.

Retinal Blood Flow After Intravitreal Bevacizumab Is A Predictive Factor For Outcomes Of Macular Edema Associated With Central Retinal Vein Occlusion

Purpose: To investigate whether retinal blood flow levels after intravitreal bevacizumab (IVB) treatment are correlated with the outcomes of patients with macular edema secondary to central retinal vein occlusion. Methods: This retrospective observational case study enrolled 44 cases nonischemic central retinal vein occlusion. In each patient, visual acuity, central retinal thickness, and mean blur rate, which was measured by laser speckle flowgraphy and represents retinal blood flow velocity, were examined. Results: At the end of the follow-up period (19.8 ± 8.8 months), 4 of 44 eyes (9.1%) converted to the ischemic type (converted group), whereas 40 (90.9%) remained unchanged (nonischemic group). Mean central retinal thickness significantly decreased and mean visual acuity significantly improved at 1 month after the first IVB injection in each group. Mean mean blur rate in the nonischemic group significantly increased, whereas it was unchanged in the converted group. The difference between the two groups was already significant after the first IVB injection. Subsequently, visual acuity worsened in the converted group. Multiple linear regression analysis indicated that the strongest correlation was between the last visual acuity and the last mean blur rate. Conclusion: Blood flow measurements are useful for evaluating IVB treatments. Blood flow after IVB can predict outcomes in patients with central retinal vein occlusion.