Michiyuki Saito

Macular choroidal blood flow velocity decreases with regression of acute central serous chorioretinopathy

Aim To quantitatively evaluate the time course of macular choroidal blood flow velocity in acute central serous chorioretinopathy (CSC). Methods This retrospective observational case series included 21 eyes of 20 patients (17 men, 3 women; mean age, 53.0 years) with treatment-naïve acute CSC. Laser speckle flowgraphy was performed to calculate macular mean blur rate (MBR), an indicator of relative blood flow velocity at the first visit, 3 and 6 months thereafter. Changes in average MBR values were compared with visual improvement at 6 months. Results Subretinal fluid completely resolved in all eyes within 6 months, while best-corrected visual acuity (BCVA) significantly improved at 6 months compared to the initial BCVA. During the follow-up period, the average MBR significantly decreased to 92.8% and 82.3% at 3 and 6 months, respectively, against baseline (100%). Importantly, there was a negative correlation between the BCVA recovery and the MBR decrease, showing the possible association of MBR increase with poor visual prognosis. Multiple regression analysis demonstrated no significant correlation between MBR and ocular perfusion pressure. Conclusions These results indicate that macular choroidal blood flow velocity decreases concurrently with regression of CSC, suggesting a validity of choroidal blood flow elevation in the pathogenesis of acute CSC.

Elevated choroidal blood flow velocity during systemic corticosteroid therapy in Vogt-Koyanagi-Harada disease

Purpose:  Laser speckle flowgraphy (LSFG) can be used to non‐invasively visualize the haemodynamics of choroidal circulation and the vascular pattern. The purpose of this study was to examine the ability of LSFG to quantitatively evaluate blood flow velocity at the macula in patients with Vogt–Koyanagi–Harada (VKH) disease before and after systemic corticosteroid therapy.

Correlation between decreased choroidal blood flow velocity and the pathogenesis of acute zonal occult outer retinopathy.

To evaluate changes of choroidal circulation quantitatively using laser speckle flowgraphy in patients with acute zonal occult outer retinopathy.

Pulse Waveform Changes in Macular Choroidal Hemodynamics With Regression of Acute Central Serous Chorioretinopathy.

PURPOSE To quantitatively evaluate the pulse waveform changes in macular choroidal blood flow by using laser speckle flowgraphy (LSFG) with regression of acute central serous chorioretinopathy (CSC). METHODS This retrospective observational case series included 20 eyes of 20 patients with acute CSC. Laser speckle flowgraphy was performed at baseline and after 6 months. On the LSFG monochrome map, automatically divided 5 × 5 grid segments within the macula were classified into predominantly delayed filling (PDF) or minimally or no delayed filling (MDF) areas according to the degree of choroidal filling delay on early-phase indocyanine green angiography. The average mean blur rate (MBR) and the pulse waveform parameters, including the skew and blowout time (BOT), were compared between the total PDF and MDF areas during follow-up. RESULTS The average MBR significantly decreased in both PDF (P = 0.005) and MDF (P < 0.001) areas during follow-up; in both areas, the skew decreased (P < 0.001 and P = 0.006, respectively) and BOT increased (P < 0.001 for each), showing significant reduction in vascular resistance at 6 months. The degree of the changes in the skew and BOT was significantly larger (P = 0.02 and P < 0.001, respectively) in the PDF area than in the MDF area. CONCLUSIONS Changes in the skew and BOT, indices for vascular resistance, confirmed the involvement of circulatory disturbance at the acute stage of CSC. The present findings suggested that the pathogenesis of CSC stems from imbalanced distribution of choroidal blood flow due to augmented vascular resistance.

Impaired Circulation in the Thickened Choroid of a Patient with Serpiginous Choroiditis

Serpiginous choroiditis is a choroiditis that shows centrifugal serpiginous extension outward from the optic disc, and is speculated to primarily affect the choriocapillaris and retinal pigment epithelium. Photoreceptor inner segment and outer segment junction (IS/OS) loss and increased reflectance of the choroid have been reported on spectral-domain optical coherence tomography; however, there have been no reports on detailed choroidal morphology. Indocyanine green angiography (ICGA) is a useful method to assess the activity of choroidal lesions in serpiginous choroiditis. However, ICGA may rarely cause anaphylactic shocks. Therefore, alternative noninvasive tools are needed for patients allergic to contrast agents, because serpiginous choroiditis often recurs with a chronic clinical course. Laser speckle flowgraphy (LSFG) can be used for noninvasive evaluation of circulation of ocular tissues and calculation of the mean blur rate (MBR), a quantitative index of relative blood flow velocity. Because the MBR is believed to originate mainly from the choroid, the value is associated with choroidal circulation hemodynamics. Composite map images of the MBR can be used for noninvasive visualization of choroidal vasculature, and the resolution is comparable to that of ICGA. Although LSFG does not provide an absolute value for the blood flow, this technique has the advantage of allowing precise and repeated measurements of choroidal circulation at various intervals during the time course of diseases. We have recently revealed that the MBR decreased in the acute stage of the choroidal inflammatory diseases, including Vogt-Koyanagi-Harada disease and acute zonal occult outer retinopathy, whereas it increased in acute central serous chorioretinopathy due to a noninflammatory (i.e. sympathetic or adrenergic) etiology. Thus, investigation into the pattern of the MBR changes during the time course of a disease appears meaningful not only to evaluate its activity but to elucidate its pathogenesis. Here we report new observations by using LSFG and enhanced-depth imaging optical coherence tomography (EDI-OCT) in a patient with serpiginous choroiditis. A 40-year-old woman was referred to our hospital for assessment of a choroidal abnormality detected at another hospital despite no subjective symptoms. The patient had no remarkable medical or family history. Visual acuities were 1.2 OD and 1.5 OS. Her left eye was normal. There were no abnormal findings in the anterior chamber or anterior vitreous of the right eye, but funduscopic examination showed yellow-white patchy geographic choroiditis plaques with a serpiginous distribution outward from the optic disc (Figure 1a). Fluorescein angiography showed initial faint hypofluorescent patches with poorly defined borders and late staining within the choroiditis plaques (Figure 1b). ICGA showed hypofluorescence from the initial phase corresponding to the plaques (Figure 1c). These angiographic findings were compatible with the active phase of serpiginous choroiditis. Serological test results and antibody titers for syphilis, toxoplasmosis, cytomegalovirus, herpes simplex virus, and herpes zoster virus were negative. QuantiFERON was also negative and chest x-ray showed no abnormalities. Serum angiotensin-

Increased macular choroidal blood flow velocity during systemic corticosteroid therapy in a patient with acute macular neuroretinopathy.

Purpose The precise mechanism causing outer retinal damage in acute macular neuroretinopathy (AMN) remains unclear. In this study, choroidal blood flow velocity was quantitatively evaluated using laser speckle flowgraphy (LSFG) in a patient with AMN who received systemic corticosteroid therapy. Methods Corticosteroids were systemically administrated across 4 months for an AMN patient. LSFG measurements were taken ten consecutive times before treatment and at 1 week and 1, 3, and 10 months after the onset of therapy. The square blur rate, a quantitative index of relative blood flow velocity, was calculated using LSFG in three regions: Square 1, the macular lesion with findings of severe multifocal electroretinography amplitude reduction, and Squares 2 and 3, funduscopically normal-appearing retinal areas with findings of moderate and mild multifocal electroretinography amplitude reduction, respectively. Results The AMN lesion gradually decreased after treatment and improved results were detected on the Amsler chart, as well as on optical coherence tomography and scanning laser ophthalmoscopy. When the changing rates of the macular flow were compared with the mean square blur rate level before treatment (100%), 14.6%, 24.5%, 12.9%, and 16.3% increases were detected in Square 1 (macular lesion) at 1 week and 1, 3, and 10 months after treatment, respectively. Similarly, in Square 2 (normal-appearing area next to the lesion), 12.6%, 18.6%, 6.7%, and 8.3% increases were also noted at 1 week and 1, 3, and 10 months after treatment, respectively. In Square 3 (normal-appearing area apart from the lesion), 16.0%, 15.1%, 19.1%, and 3.8% increases were measured at 1 week and 1, 3, and 10 months after treatment, respectively. Conclusion In a patient with AMN, choroidal blood flow velocity at the lesion site, which was examined with LSFG, sequentially increased during systemic corticosteroid therapy, together with improvement of visual function. The present findings suggest that choroidal circulation impairment relates to the pathogenesis of AMN, extending over a wider area in the posterior pole than the site of an AMN lesion per se.

A case of paraneoplastic optic neuropathy and outer retinitis positive for autoantibodies against collapsin response mediator protein-5, recoverin, and α-enolase

BackgroundSpecific cross-reacting autoimmunity against recoverin or collapsin response mediator protein (CRMP)-5 is known to cause cancer-associated retinopathy or paraneoplastic optic neuropathy, respectively. We report a rare case with small cell lung carcinoma developing bilateral neuroretinitis and unilateral focal outer retinitis positive for these antibodies.Case presentationA 67-year-old man developed bilateral neuroretinitis and foveal exudation in the right eye. Optical coherence tomography showed a dome-shaped hyperreflective lesion extending from inner nuclear layer to the photoreceptor layer at the fovea in the right eye. Single-flash electroretinography showed normal a-waves in both eyes and slightly reduced b-wave in the left eye. Results of serological screening tests for infection were within normal limits. The patient’s optic disc swelling and macular exudation rapidly improved after oral administration of prednisolone. Systemic screening detected lung small cell carcinoma and systemic chemotherapy was initiated. Immunoblot analyses using the patient’s serum detected autoantibodies against recoverin, CRMP-5, and α-enolase, but not carbonic anhydrase II. Neuroretinitis once resolved after almost remission of carcinoma on imaging but it recurred following the recurrence of carcinoma.ConclusionsThe development of neuroretinitis in this cancer patient with anti-retinal and anti-optic nerve antibodies depended largely on the cancer activity, suggesting the possible involvement of paraneoplastic mechanisms. Patients with paraneoplastic optic neuropathy and retinopathy are likely to develop autoimmune responses against several antigens, thus leading to various ophthalmic involvements.

Acute Zonal Occult Outer Retinopathy in Japanese Patients: Clinical Features, Visual Function, and Factors Affecting Visual Function

Purpose To evaluate the clinical features and investigate their relationship with visual function in Japanese patients with acute zonal occult outer retinopathy (AZOOR). Methods Fifty-two eyes of 38 Japanese AZOOR patients (31 female and 7 male patients; mean age at first visit, 35.0 years; median follow-up duration, 31 months) were retrospectively collected: 31 untreated eyes with good visual acuity and 21 systemic corticosteroid-treated eyes with progressive visual acuity loss. Variables affecting the logMAR values of best-corrected visual acuity (BCVA) and the mean deviation (MD) on Humphrey perimetry at initial and final visits were examined using multiple stepwise linear regression analysis. Results In untreated eyes, the mean MD at the final visit was significantly higher than that at the initial visit (P = 0.00002). In corticosteroid-treated eyes, the logMAR BCVA and MD at the final visit were significantly better than the initial values (P = 0.007 and P = 0.02, respectively). The final logMAR BCVA was 0.0 or less in 85% of patients. Variables affecting initial visual function were moderate anterior vitreous cells, myopia severity, and a-wave amplitudes on electroretinography; factors affecting final visual function were the initial MD values, female sex, moderate anterior vitreous cells, and retinal atrophy. Conclusions Our data indicated that visual functions in enrolled patients significantly improved spontaneously or after systemic corticosteroids therapy, suggesting that Japanese patients with AZOOR have good visual outcomes during the follow-up period of this study. Furthermore, initial visual field defects, gender, anterior vitreous cells, and retinal atrophy affected final visual functions in these patients.

Clinical and histological evaluation of large macular hole surgery using the inverted internal limiting membrane flap technique

Purpose The aims of this study were to analyze optical coherence tomography (OCT) imaging of large macular holes (MHs) treated with inverted internal limiting membrane (ILM) flap technique and to perform a histological examination of an ILM-like membrane tissue obtained during vitrectomy. Patients and methods This is a retrospective observational case study. Nine patients, comprising of five males and four females, showing large and myopic MHs, underwent pars plana vitrectomy (PPV) with inverted ILM flap technique assisted by brilliant blue G (BBG) staining. Ophthalmological findings including visual acuity and OCT were investigated based on medical records. Formalin-fixed paraffin-embedded tissue section of an ILM-like membrane was submitted for immunohistochemistry with glial fibrillary acidic protein (GFAP). Results ILM was clearly stained with BBG in eight patients, whereas the ILM in one case revealed no staining with BBG during PPV. Visual acuities improved to >0.2 LogMAR in six patients. The complete closure of MH following PPV with inverted ILM technique was eventually achieved in all patients determined by OCT imaging (100%). Only one patient showed recovery of ellipsoid zone and interdigitation zone following the surgery. Elongation of outer nuclear layer was noted in three eyes. The ILM-like membrane not stained with BBG histologically revealed an amorphous structure admixed with GFAP-positive mononuclear cell infiltration. Conclusion PPV with inverted ILM flap technique achieved 100% closure rates with favorable configuration at an initial surgery in large MHs. Our histopathological data also suggest that even BBG staining-negative membrane may be a useful material for autologous transplantation to the hole.

Retinal outer layer thickness increases with regression of multiple evanescent white dot syndrome and visual improvement positively correlates with photoreceptor outer segment length

Editor, M ultiple evanescent white dot syndrome (MEWDS) is a unilateral chorioretinal disease characterized by multiple small subretinal white dots extending from the posterior pole to the midperiphery (Jampol et al. 1984). Spectral-domain optical coherence tomography (SD-OCT) demonstrates impairments in outer retinal morphology that recover along with improvements in visual function (Li & Kishi 2009). However, little is known about how inner and outer retinal layer thicknesses change with regression of MEWDS or how this correlates with visual outcomes. Here we show, using SD-OCT, the time–course of changes in retinal layer thicknesses in MEWDS. This study included 8 eyes from 8 patients (1man and 7women;mean age, 31.6 13.6 years) with MEWDS. All enrolled cases were unilateral. Using the C-scanmode (6 9 6 mmmacular thickness map) of SD-OCT (RS-3000 or RS3000 Advance; NIDEK, Gamagori, Japan), the whole (the inner limiting membrane [ILM] to the retinal pigment epithelium [RPE]), inner (the ILMto the inner plexiform layer [IPL]) and outer (the outer nuclear layer to the RPE) retinal layer thicknesses were automatically measured at baseline and 1 and 3 months after baseline in MEWDS eyes and at baseline and 3 months in unaffected fellow eyes (Fig. 1A), as described previously (Hashimoto et al. 2014). Moreover, the inner retinal layer was divided into two layers (i.e. the ILM