A comparison of laparoscopic procedures performed by novice medical students using 8K ultra-high-definition/two-dimensional and 2K high-definition/three-dimensional monitors.

PURPOSE: 8K Ultra-high-definition (UHD) imaging has been developed in accordance with the progression of imaging technologies. We evaluated laparoscopic procedures performed by novice medical students using 2K/two-dimensional (2D), 2K/three-dimensional (3D) and 8K/2D monitors, with a particular focus on depth perception. METHODS: Nine medical students were enrolled. They performed two tasks using 2K/2D, 2K/3D and 8K/2D monitors. In Task 1, they were asked to grasp three metal rods with forceps using each hand. In Task 2, they were asked to grasp a metal rod with forceps held in the right hand, pass the metal rod through a metal ring and transfer it to their left hand. RESULTS: In Task 1, when performed with the dominant hand, the procedures performed using 2K/3D took a significantly shorter time than those performed using 8K/2D (P = 0.04). However, there was no significant difference among the three groups in the time required for procedures performed by the non-dominant hand. In Task 2, the procedure time with 2K/2D was significantly longer than that with 2K/3D or 8K/2D (P = 0.02). CONCLUSION: 2K/3D showed superior utility to 8K/2D for performing forceps procedures using the dominant hand. However, when the movement of both hands was coordinated ("bi-hand coordination"), the laparoscopic procedures were performed almost as deftly with 8K/2D and 2K/3D.

Association of Rare CYP39A1 Variants With Exfoliation Syndrome Involving the Anterior Chamber of the Eye.

Importance: Exfoliation syndrome is a systemic disorder characterized by progressive accumulation of abnormal fibrillar protein aggregates manifesting clinically in the anterior chamber of the eye. This disorder is the most commonly known cause of glaucoma and a major cause of irreversible blindness. Objective: To determine if exfoliation syndrome is associated with rare, protein-changing variants predicted to impair protein function. Design, Setting, and Participants: A 2-stage, case-control, whole-exome sequencing association study with a discovery cohort and 2 independently ascertained validation cohorts. Study participants from 14 countries were enrolled between February 1999 and December 2019. The date of last clinical follow-up was December 2019. Affected individuals had exfoliation material on anterior segment structures of at least 1 eye as visualized by slit lamp examination. Unaffected individuals had no signs of exfoliation syndrome. Exposures: Rare, coding-sequence genetic variants predicted to be damaging by bioinformatic algorithms trained to recognize alterations that impair protein function. Main Outcomes and Measures: The primary outcome was the presence of exfoliation syndrome. Exome-wide significance for detected variants was defined as P < 2.5 × 10-6. The secondary outcomes included biochemical enzymatic assays and gene expression analyses. Results: The discovery cohort included 4028 participants with exfoliation syndrome (median age, 78 years [interquartile range, 73-83 years]; 2377 [59.0%] women) and 5638 participants without exfoliation syndrome (median age, 72 years [interquartile range, 65-78 years]; 3159 [56.0%] women). In the discovery cohort, persons with exfoliation syndrome, compared with those without exfoliation syndrome, were significantly more likely to carry damaging CYP39A1 variants (1.3% vs 0.30%, respectively; odds ratio, 3.55 [95% CI, 2.07-6.10]; P = 6.1 × 10-7). This outcome was validated in 2 independent cohorts. The first validation cohort included 2337 individuals with exfoliation syndrome (median age, 74 years; 1132 women; n = 1934 with demographic data) and 2813 individuals without exfoliation syndrome (median age, 72 years; 1287 women; n = 2421 with demographic data). The second validation cohort included 1663 individuals with exfoliation syndrome (median age, 75 years; 587 women; n = 1064 with demographic data) and 3962 individuals without exfoliation syndrome (median age, 74 years; 951 women; n = 1555 with demographic data). Of the individuals from both validation cohorts, 5.2% with exfoliation syndrome carried CYP39A1 damaging alleles vs 3.1% without exfoliation syndrome (odds ratio, 1.82 [95% CI, 1.47-2.26]; P < .001). Biochemical assays classified 34 of 42 damaging CYP39A1 alleles as functionally deficient (median reduction in enzymatic activity compared with wild-type CYP39A1, 94.4% [interquartile range, 78.7%-98.2%] for the 34 deficient variants). CYP39A1 transcript expression was 47% lower (95% CI, 30%-64% lower; P < .001) in ciliary body tissues from individuals with exfoliation syndrome compared with individuals without exfoliation syndrome. Conclusions and Relevance: In this whole-exome sequencing case-control study, presence of exfoliation syndrome was significantly associated with carriage of functionally deficient CYP39A1 sequence variants. Further research is needed to understand the clinical implications of these findings.

Macular capillary recovery in systemic lupus erythematosus complicated by Kikuchi-Fujimoto disease.

PURPOSE: Few case reports have described vaso-occlusive retinopathy in systemic lupus erythematosus (SLE) using optical coherence tomography (OCT) angiography. Here we report the clinical features of a patient with SLE, complicated by Kikuchi-Fujimoto disease, who developed vaso-occlusive retinopathy. We then describe the subsequent recovery of the macular capillaries as assessed by OCT angiography. CASE: A 16-year-old male was referred to us with fever, a 1-month history of violaceous red papules and erythematous plaques on his face and a painful nodule in his right neck. We diagnosed him with SLE complicated by Kikuchi-Fujimoto disease through physiological assessment and histology from his neck lymph node and chin skin. Systemic steroids were prescribed as treatment. After remission, his fever and cervical lymph node swelling with pain recurred and he developed blurred inferior vision in his left eye. His best-corrected visual acuities were 1.0 and 0.1 in the right and left eyes, respectively. Extensive cotton wool spots were observed in the right fundus, and retinal capillary occlusions were detected by OCT angiography of the left eye. We diagnosed this case as vaso-occlusive retinopathy with SLE and increased immunosuppressive treatment together with anticoagulation therapy. Macular capillaries, observed by OCT angiography, gradually recovered function following assessment at 7 and 16 months post-onset of the vaso-occlusive retinopathy. CONCLUSIONS: We reported a 1½-year course of vaso-occlusive retinopathy in a patient with SLE complicated by Kikuchi-Fujimoto disease. Occlusion of the retinal vasculature and the subsequent recovery of circulation are clearly observed by OCT angiography.

Reperfusion of the choriocapillaris observed using optical coherence tomography angiography in hypertensive choroidopathy.

PURPOSE: Optical coherence tomography angiography (OCTA) can visualize the vascular status of the choriocapillaris noninvasively and separately from the other vascular beds. We describe focal ischemia in the choriocapillaris and reperfusion of the area in hypertensive choroidopathy using en-face OCTA. CASE: A 32-year-old woman diagnosed with pregnancy-induced hypertension presented with acute anorthopia in the right eye after delivery via Caesarian section. Fundus examination showed an Elschnig's spot and serous retinal detachment (SRD) in the inferior perifoveal region. Early-phase fluorescein angiography and indocyanine green angiography images showed focally delayed choroidal perfusion, i.e., regional absence of choroidal flush. OCTA also showed a focal dark area in a slab of the choriocapillaris corresponding to the angiographic observation. After oral antihypertensive treatment, the dark area on the OCTA image of the choriocapillaris resolved over time in association with the resolving SRD. CONCLUSION: En-face OCTA is a useful technology to follow noninvasively the circulatory status of the choriocapillaris in hypertensive choroidopathy.

Short-term effects of intravitreal ranibizumab therapy on diabetic macular edema.

BACKGROUND: The short-term effects of intravitreal ranibizumab (IVR) on diabetic macular edema (DME) remains unclear. We assessed the short-term effects of IVR on DME. METHODS: Eighteen eyes of 14 patients with DME were enrolled in this prospective interventional case series. After intravitreal ranibizumab was injected into treatment-naïve eyes with DME, we measured the foveal thickness (FT) before and 2 h, 1 day, 1 week, and 1 month later and the best-corrected visual acuity (BCVA) at all times except 2 h and compared the changes to baseline (ΔFT and ΔVA). RESULTS: The mean FT decreased significantly (p < 0.0001) from 452 ± 77 to 429 ± 65 microns after 2 h. The mean logarithm of the minimum angle of resolution BCVA improved significantly (p = 0.032) after 1 month from 0.41 ± 0.24 to 0.32 ± 0.21 (20/51 to 20/42, Snellen equivalent). The ΔFT after 2 h was significantly (r = 0.53, p = 0.025) correlated with the ΔFT after 1 month. The ΔVA after 1 day was significantly (r = 0.59, p = 0.01) correlated with the ΔVA after 1 month. CONCLUSIONS: The structural effects of IVR for DME occurred within 2 h, whereas the functional effects occurred after 1 month. The short-term effects (within 1 day) of IVR may predict the therapeutic outcome 1 month after IVR in patients with DME. TRIAL REGISTRATION: The trial registration number: UMIN000026118 (Feb/13/2017). Retrospectively registered.

Correlation between short- and long-term effects of intravitreal ranibizumab therapy on macular edema after branch retinal vein occlusion: a prospective observational study.

BACKGROUND: The correlation between the short- and long-term effects of intravitreal ranibizumab (IVR) on macular edema after branch retinal vein occlusion (BRVO) remains unclear. We assessed the correlation between the short- and long-term effects of IVR on macular edema after BRVO. METHODS: Twenty-one eyes with macular edema after BRVO were enrolled in this prospective observational study. We measured the foveal thickness (FT) and the best-corrected visual acuity (BCVA) before, 1 day after, and 1 month after IVR (0.5 mg) and then at least every 2 months thereafter until 6 months after the injection. If the macular edema recurred, another injection was administered. The primary endpoint was the change from baseline in the BCVA (ΔVA). RESULTS: The mean logarithm of the minimum angle of resolution VA improved significantly (p = 0.01, p < 0.0001, respectively) after 1 day from 0.65 ± 0.28 to 0.51 ± 0.21 (20/89 to 20/63, Snellen equivalent) and after 6 months to 0.29 ± 0.24 (20/39, Snellen equivalent). The mean FT decreased significantly (p < 0.0001) after 1 day from 482 ± 85 µm to 349 ± 75 µm and after 6 months to 305 ± 84 µm. The 1-day VA was significantly (r = 0.68, p = 0.0007) positively correlated with the 6-month VA. The 1-day ΔVA was significantly (r = 0.79, p < 0.0001) positively correlated with the 6-month ΔVA. CONCLUSIONS: The short-term effects of IVR may predict the long-term effects of IVR in macular edema secondary to BRVO. TRIAL REGISTRATION: Trial registration number: UMIN000027003 . Retrospectively registered. (April/15/2017).

Amniotic Membrane Transplantation for Corneal and Conjunctival Diseases: Classification of Application and Outcomes from Analysis of 95 cases.

Purpose: To evaluate the indications and outcomes of amniotic membrane (AM) transplantation for corneal and conjunctival diseases. Subjects and methods: Ninety-five eyes of ninety patients who underwent AM transplantation between January 2007 and May 2016 were included in this study. The surgical procedures, diagnosis and postoperative outcomes were investigated retrospectively. Results: Transplantation was conducted in three surgical procedures. AM patch, for the promotion of corneal re-epithelialization, was performed in 14 cases with persistent epithelial defects. Thirteen cases healed with total epithelialization. Corneal perforation was noted in Stevens-Johnson syndrome and cured with keratoplasty. AM graft for basement membrane supply, was performed in 72 cases. Of these, 32 cases had been followed for at least one year after AM graft out of which pterygium recurred at one year in 5. Conjunctival tumor recurred in 3 out of 17 cases, and was treated with a repeated of AM graft. AM stuff for substrate supply to the deep corneal layer, was performed in 9 cases with corneal perforation. Leakage of aqueous humor was cured in all 9 cases. Seven cases had keratoplasty performed after the AM stuff and recovered completely. The other 2 cases were observed without additional surgery. There were no complications due to the AM transplantation during the course of treatment in any of the 95 cases. Conclusion: AM transplantation is applied in three different procedures. Each of these was effective in achieving the corneal and conjunctival reconstruction designed for it.

Vascular rarefaction at the choriocapillaris in acute posterior multifocal placoid pigment epitheliopathy viewed on OCT angiography.

Few cases have been reported describing choroidal vasculature in acute posterior multifocal placoid pigment epitheliopathy (APMPPE) using optical coherence tomography (OCT) angiography. We report choroidal vasculature changes in an APMPPE patient with the clinical course characterized by OCT angiography. A 39-year-old female was referred to us for bilateral multiple white spots in bilateral fundus. The best-corrected visual acuity was 20/20 in the right eye and 20/50 in the left eye. Multiple yellowish-white placoid lesions were observed in bilateral fundus, and fluorescein angiography showed a "block early, stain late" pattern at the placoid lesions characteristic of APMPPE. The placoid lesion represented vascular rarefaction at the choriocapillaris in the OCT angiography en face view. While the clinical course of symptoms and most of the low vascular rarefaction lesions regressed in 6 months, some new lesions were subclinically noted. Blurred vision recurred at 9 months from the first visit, and the vascular rarefaction lesions developed in different areas than those observed in the initial visit. Multiple yellowish-white placoid lesions in an APMPPE patient represented vascular rarefaction at the choriocapillaris in OCT angiography. The vascular rarefaction recovered and then recurred during the clinical course. OCT angiography can visualize changes of the choroidal vessels during APMPPE.

Long-term outcome of amniotic membrane transplantation combined with mitomycin C for conjunctival reconstruction after ocular surface squamous neoplasia excision.

The aim of the study is to evaluate the long-term clinical results of amniotic membrane transplantation (AMT) combined with mitomycin C (MMC) for reconstruction of conjunctival defects created during the excision of ocular surface squamous neoplasia (OSSN). Eight consecutive eyes of seven patients (five males and two females; mean age, 64 ± 19 years) treated by one surgeon (KH) were included in this study. AMT was performed after excision of a mass region, along with 0.04 % MMC treatment for the exposed sclera. The tumor size, histopathological retrieval, AM graft size after tumor excision, recurrence, and postoperative complications were recorded. During a mean postoperative follow-up period of 60.9 ± 14.6 months (range 36-78 months), the ocular surfaces completely re-epithelialized in all cases. The median size of the tumor was 44.4 ± 21.2 mm2 (range 13-67 mm2). The histopathological diagnoses were five cases of squamous cell carcinoma in situ (SCC in situ) and three cases of dysplasia. The median size of the AM graft after tumor excision was 100.8 ± 32.7 mm2 (range 49-151 mm2). A case of recurrent SCC in situ with a preoperative history of using MMC eye drops developed further corneal limbal deficiency and was treated with therapeutic soft contact lenses. A case of dysplasia with a history of large pterygial excision developed symblepharon postoperatively was treated with AMT 6 months after tumor excision. The tumors recurred in two eyes with SCC in situ and were successfully treated with continuous AMT and MMC. No severe complications, such as infections, corneal or scleral thinning, or ulceration developed in all cases. The combination of AMT and MMC is effective for safe reconstruction over the long-term after the excision of OSSN with postoperative careful observation and treatment. In recurrent tumor excision cases, AMT is a suitable technique for repeated ocular surface reconstruction.

Comparison of intraocular pressure variability in glaucoma measured by multiple clinicians with those by one clinician.

To compare the intraocular pressure (IOP) variability measured by multiple clinicians with those by one clinician. Forty-seven of 227 consecutive patients with glaucoma who had been examined routinely for over 12 months without changes in antiglaucoma medications at Asahikawa Medical University were included. Patients were assigned to one of two groups based on whether they had been followed by multiple or one clinician. One eye of each patient was evaluated. The IOPs obtained using Goldmann applanation tonometry were evaluated. We used the IOP standard deviation (SD, mmHg) and coefficient of variation (CV, %) as parameters of IOP variability. The main outcome measures were the differences in SD and CV between the groups. Multiple linear regression analysis evaluated factors associated with the SD and CV. Twenty-four (51.1 %) patients were assigned to the multiple-clinicians group and 23 (48.9 %) to the single-clinician group. The mean ± SD and CV were higher in the former (1.9 ± 0.5 and 12.0 ± 3.7, respectively) than in the latter group (1.4 ± 0.3 and 10.1 ± 2.5; P = 0.0005 and 0.044, respectively). The number of treating clinicians was the factor most associated with the SD and CV (ß = 0.455, P = 0.002 and ß = 0.387, P = 0.008, respectively). The variability in the IOP measurements of patients who had been monitored by multiple clinicians was higher than in patients followed by one clinician. The factor most associated with IOP variability was the number of clinicians involved.

SHORT-TERM EFFECT OF INTRAVITREAL RANIBIZUMAB THERAPY ON MACULAR EDEMA AFTER BRANCH RETINAL VEIN OCCLUSION.

PURPOSE: To assess the short-term effect of intravitreal ranibizumab (IVR) on macular edema after branch retinal vein occlusion. METHODS: Twenty-three eyes with macular edema after branch retinal vein occlusion were enrolled in a prospective observational study. After administering one IVR injection (0.5 mg) for the first time, the authors measured the foveal thickness (FT) before and 2 hours, 1 and 3 days, 1 week, and 1 month later and the best-corrected visual acuity at all times except 2 hours, and determined the changes from baseline (ΔFT and ΔVA). RESULTS: The mean FT decreased significantly (P < 0.0001) from 522 ± 131 µm to 458 ± 96 µm after 2 hours. The mean logarithm of the minimum angle of resolution (logMAR) visual acuity improved significantly (P < 0.05) after 1 day from 0.69 ± 0.40 to 0.55 ± 0.34 (20/98-20/70, Snellen equivalent). The ΔFT after 2 hours was significantly positively correlated with the ΔFT after 1 week (r = 0.76, P < 0.001) and 1 month (r = 0.67, P < 0.001). The ΔVA after 1 day was correlated positively with the ΔVA after 1 week (r = 0.80, P < 0.001) and 1 month (r = 0.59, P < 0.01). CONCLUSION: Structural and functional effects of IVR for branch retinal vein occlusion occurred within 1 day. The short-term effects of IVR may predict the outcome of the therapy at 1 week and 1 month after IVR in macular edema secondary to branch retinal vein occlusion.

SYSTEMIC RISK FACTORS IN BILATERAL PROLIFERATIVE DIABETIC RETINOPATHY REQUIRING VITRECTOMY.

PURPOSE: The visual outcome after vitrectomy for proliferative diabetic retinopathy (PDR) is often poor. Bilateral vitrectomy has been especially associated with a poor visual prognosis in patients with PDR. The authors investigated the systemic risk factors for PDR requiring bilateral vitrectomy compared with unilateral vitrectomy. METHODS: The authors retrospectively reviewed 86 consecutive patients with Type 2 diabetes mellitus with PDR who underwent vitrectomy. These patients were divided into 2 groups: bilateral vitrectomy within 1 year (n = 25) and unilateral vitrectomy (n = 61). The authors compared the systemic risk factors: age, sex, duration of diabetes, hemoglobin A1c, body mass index, estimated glomerular filtration rate, uric albumin, hypertension, dyslipidemia, history of ischemic heart disease, arteriosclerosis obliterans, and smoking. RESULTS: There were significantly more cases with severe renal dysfunction in the bilateral vitrectomy group compared with the unilateral one (estimated glomerular filtration rate <30 mL/minute/1.73 m; bilateral cases = 5/25; unilateral cases = 2/61; P = 0.02). CONCLUSION: The authors found that severe renal dysfunction may be a risk factor in PDR requiring bilateral vitrectomy, indicating that careful attention needs to be paid to prevent the progression of diabetic retinopathy to severe PDR in the other eye if patients have severe unilateral PDR and severe renal dysfunction.

Enhanced vitreous imaging optical coherence tomography in primary macular holes.

The aim of the current pilot study is to investigate the efficacy of a novel enhanced vitreous imaging (EVI) in primary macular holes (MHs) using a spectral-domain optical coherence tomography (SD-OCT). Thirty-four eyes of 32 consecutive patients with a MH were examined in one time cross-sectional study. The vitreomacular interface was assessed using SD-OCT with conventional and EVI technique. Twenty-three of the 34 eyes did not show a Weiss ring, and in 22 of those, we observed a MH with an open roof or operculum and a detached posterior vitreous cortex with conventional vitreous imaging. Using EVI-OCT, we visualized the reflection of the posterior vitreous with a vitreopapillary attachment. One of the 23 eyes without a Weiss ring had a central round retinal defect without an operculum, and the conventional SD-OCT showed an empty vitreous, suggesting a complete posterior vitreous detachment. However, the EVI-OCT revealed the reflection of the posterior vitreous, and the cortex appeared to still be completely attached. In all the 23 eyes without a Weiss ring, EVI-OCT detected the reflection of the posterior vitreous and vitreopapillary attachment. In all 11 eyes with a Weiss ring (stage 4 hole), EVI-OCT showed an optically empty space in the posterior vitreous cavity without a vitreopapillary attachment. EVI-OCT may be a new reliable method for preoperative evaluations to determine the presence or absence of a complete posterior vitreous detachment in macular diseases with an indistinct Weiss ring.

Linezolid-induced optic neuropathy with a rare pathological change in the inner retina.

We report a case of linezolid-induced optic neuropathy with transient microcystic spaces in the inner retina. We observed the retina using Fourier-domain optical coherence tomography (FD-OCT) in a patient with linezolid-induced optic neuropathy. A 49-year-old woman presented to our department with a 1-week history of bilateral photophobia. At the first visit, her best-corrected visual acuity (VA) was 0.6 in the right eye and 0.5 in the left eye. She had moderate optic disk edema and central scotomas bilaterally. FD-OCT showed bilateral microcystic spaces in the retina. Microcystic spaces were seen in the retinal nerve fiber layer (RNFL) and at the border of the RNFL and the retinal ganglion cell layer. Magnetic resonance imaging and laboratory tests showed no positive findings except for an elevated lactic acid level. One week after the first visit, the VA levels decreased to 0.06 and 0.07 in the right and left eyes, respectively. Because the patient had a 7-month history of linezolid treatment for persistent pyogenic arthritis, we suspected linezolid-induced optic neuropathy and immediately terminated treatment with this drug. The optic disk edema and the microcystic spaces in the retina resolved, and the VA improved to 1.2 at 6 weeks after linezolid withdrawal. Microcystic spaces, which resolved with linezolid withdrawal, were observed in linezolid-induced optic neuropathy. The microcystic spaces in the inner retina can be the first retinal sign of some optic neuropathies.

Vasodilatory mechanisms of unoprostone isopropyl in isolated porcine retinal arterioles.

PURPOSE: To clarify the vasodilatory mechanism of unoprostone isopropyl (UI), we examined its effects on the retinal microvascular diameter to determine the dependence on the endothelium and/or smooth muscle to reveal the signaling mechanisms involved in this vasomotor activity. METHODS: Porcine retinal arterioles were isolated, cannulated, and pressurized without flow in vitro. Video microscopic techniques recorded the diametric responses to UI. RESULTS: The retinal arterioles dilated in response to UI in a dose-dependent (100 pM-10 µM) manner. The nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) inhibited UI-induced vasodilation. The large-conductance Ca2+-activated K channel (BKCa channel) blocker iberiotoxin also inhibited UI-induced vasodilation. The residual vasodilation after L-NAME was eliminated with co-administration of iberiotoxin. CONCLUSIONS: UI elicits dilation of the retinal arterioles mediated by NO release and BKCa channel activation.

Effect of intravitreal Rho kinase inhibitor ripasudil (K-115) on feline retinal microcirculation.

Ripasudil (K-115) is a novel Rho kinase inhibitor with a potent intraocular pressure-lowering effect. However, it is unclear whether ripasudil affects the retinal blood flow (RBF). We investigated the effect of ripasudil on feline retinal microcirculation. Ripasudil (5 µM, 50 µM or 5 mM; n = 5 each concentration) or vehicle (PBS; n = 5) was injected intravitreally. The vessel diameter (D) and blood velocity (V) were measured by laser Doppler velocimetry simultaneously in the first-order retinal arterioles and the RBF was calculated. The measurements started 5 min before the injection and were performed every 10 min for 120 min. After the intravitreal injection, the retinal circulatory parameters did not change significantly in PBS or 5 µM of ripasudil. The blood V and RBF increased significantly compared to baseline, whereas the vessel D did not change significantly in 50 µM and 5 mM of ripasudil. The V in 50 µM, and the V and RBF in 5 mM of ripasudil significantly increased compared to those in PBS. Intravitreal administration of ripasudil increased the blood V and RBF in cats, suggesting that ripasudil has the potential to improve the retinal blood flow.

Role of Ca2+ -dependent and Ca2+ -sensitive mechanisms in sphingosine 1-phosphate-induced constriction of isolated porcine retinal arterioles in vitro.

Although sphingosine 1-phosphate (S1P), a bioactive lipid derived from activated platelets, has a variety of physiologic effects on vessels, no reports have described the effect of S1P on the retinal circulation. We examined the effect and underlying mechanism of the vasomotor action of S1P on porcine retinal arterioles. The porcine retinal arterioles were isolated, cannulated, and pressurized without flow for in vitro study. S1P-induced diameter changes were recorded using videomicroscopic techniques. S1P elicited concentration-dependent (1 nM-10 µM) vasoconstriction of the retinal arterioles that was abolished by the S1P receptor 2 (S1PR2) antagonist JTE-013. S1P-induced vasoconstriction was abolished by the Rho kinase (ROCK) inhibitor H-1152 and was inhibited partly by the protein kinase C (PKC) inhibitor Gö-6983. The inhibition of phospholipase C by U73122 and L-type voltage-operated calcium channels (L-VOCCs) by nifedipine inhibited S1P-induced vasoconstriction; a combination of both inhibitors abolished S1P-induced vasoconstriction. Furthermore, inhibition of myosin light chain kinase (MLCK) by ML-9 significantly blocked S1P-induced vasoconstriction; further coadministration of ML-9 with H-1152 or Gö-6983 abolished S1P-induced vasoconstriction. The current data suggest that S1P elicits vasoconstriction of the retinal arterioles via S1PR2 in vascular smooth muscle cells and this vasoconstriction may be mediated by the Ca2+ -sensitive pathway via activation of PKC leading to activation of ROCK and the Ca2+ -dependent pathway via activation of L-VOCCs resulting in activation of MLCK.

Changes in retinal blood flow in patients with macular edema secondary to branch retinal vein occlusion before and after intravitreal injection of bevacizumab.

PURPOSE: To investigate the effect of intravitreal bevacizumab (IVB) injections for macular edema secondary to acute branch retinal vein occlusion on the retinal microcirculation. METHODS: The study was a prospective, interventional case series. Central macular thickness using spectral-domain optical coherence tomography and retinal blood flow (RBF) in untreated eyes with macular edema secondary to acute branch retinal vein occlusion in occluded (V1) and opposite venules in affected eyes (V2) and the equivalent venules in contralateral eyes (V3), using laser Doppler velocimetry during follow-up and after IVB injection, were measured. RESULTS: In 33 eyes with acute branch retinal vein occlusion of <2 months of duration at the first visit, changes in the retinal microcirculation for 1 month was observed; the macular edema improved spontaneously, and the RBF was unchanged in 15 of 33 eyes, and the RBF increased by 23.3% in 18 eyes with persistent macular edema. Twenty-four eyes received an IVB injection (1.25 mg per 0.05 mL). The RBF did not change significantly during follow-up. In 8 of 24 eyes (33%) with improved macular edema 3 months after the treatment, the average RBF values before injection were significantly higher compared with that of eyes with recurrent edema. CONCLUSION: One IVB injection might have little effect on the retinal microcirculation in patients with macular edema secondary to acute branch retinal vein occlusion at least 3 months after the injection. However, the increased RBF in the occluded venules before injection might be associated with improved macular edema after the IVB injection.

Recurrent Vogt­Koyanagi­Harada disease with sensorineural hearing loss and choroidal thickening.

We report a case of Vogt­Koyanagi­Harada (VKH) disease that recurred with sensorineural hearing loss and choroidal thickening. We measured the choroidal thickness using enhanced-depth imaging optical coherence tomography (EDI-OCT) in a patient with VKH during corticosteroid-tapering therapy. A71-year-old male presented with fever, headache, and anorthopia associated with wavy choroidal folds and aserous retinal detachment (SRD). The EDI-OCT images showed choroidal thickening ([600 l m at the subfovea), and he was diagnosed with VKH disease. After treatment with pulsed intravenous methylprednisolone, the choroidal folds and SRD resolved and the choroidal thickness decreased. About 6 months after subsequent treatment with an oral corticosteroid started, headache, tinnitus, and sensorineural hearing loss developed, and increased choroidal thickness was observed without other evidence of increased ocular inflammation. A high-dose corticosteroid was injected and tapered, and the sensorineural hearing loss improved immediately and the choroidal thickness decreased. In the current case, sensorineural hearing loss occurred with recurrent VKH disease;however, there were no ocular inflammatory signs except for rebound choroidal thickening. Measuring the choroidal thickness using EDI-OCT can sensitively identify recurrent VKH disease.