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Diabetic retinopathy (DR) is a leading cause of blindness in the working population. Because novel therapeutic intervention require testing, there is an urgent need for reliable animal models that faithfully replicate DR. Pig eyes have many similarities to human eyes anatomically and physiologically. Thus, attempts have been made to establish porcine models of DR by surgical, pharmaceutical or genetical induction of insulin deficiency, and dietary intervention. A previous study reported a transgenic pig model of maturity onset diabetes of the young type 3 (MODY3) developed signs of severe DR such as hemorrhage and proliferative tissue at the surface of the retina. However, the course of development of DR has not been studied in detail in this model. The purpose of this study was to investigate the early phase of DR in a MODY3. MODY3 and wild-type (WT) pigs underwent fundus photography and fluorescein angiogram (FA) before they developed cataracts. Animals were euthanized at age 1, 4, 7, and 10 months. Whole-mount retina and 10-μm thick paraffinized sections were stained with isolectin B4, and vessel density was determined by MATLAB software. At 4 and 7 months, retinal arterioles were immediately cannulated, and vasomotor action was measured by incubation with bradykinin and sodium nitroprusside. In the MODY3 pigs, fasting blood sugar levels gradually increased up to 500 mg/dL. Vascular tortuosity and yellowish spindle-shaped lesions were confirmed in MODY3 pigs at the age of 7 months; however, no microaneurysms were detected on FA. Compared with age-matched WT pigs, MODY3 pigs showed a significant decrease in blood vessel density in the intermediate and deep vascular plexus at 4 and 7 months of age and a slight decrease in capillary density in the superficial vascular plexus at 7 months of age. In MODY3 pigs, electron microscopy revealed thickening of the capillary basement membrane and leukostasis in the major blood vessels at 10 months of age. Bradykinin-induced dilation of retinal arterioles was diminished in MODY3 pigs as early as 7 months of age. Within 1 year after birth, MODY3 pigs show all typical early vascular lesions of diabetes except for microaneurysm formation. This pilot study suggests that the MODY3 pigs may serve as a suitable DR model to test effects of newly developed compounds on DR.

Herein, we report the longitudinal observation of a case with reopening of the macular hole associated with a lamellar macular hole-associated epiretinal proliferation (LHEP) followed by spontaneous closure in patients with stage 2 idiopathic macular hole. A 64-year-old woman was referred for the decreased visual acuity (VA) and acute anorthopia in the right eye. Funduscopy and optical coherence tomography (OCT) showed stage 2 full-thickness macular hole without posterior vitreous detachment (PVD) and operculum formation. Her best-corrected visual acuity (BCVA) was 20/32. One month later, the diameter of the macular hole was getting small and VA improved. Six months later, the macular hole was treated spontaneously with the attached hyaloid membrane to the macula by OCT and the BCVA improved to 20/20. Fourteen months after the first visit, the BCVA decreased to 20/50 and the patient was diagnosed with stage 4 macular hole with complete PVD. OCT showed full-thickness macular hole with a LHEP in the right eye. After 25G-gauge vitrectomy with the peeling of internal limiting membrane (ILM) and LHEP, the macular hole was closed and BCVA finally improved to 20/25. Spontaneous macular hole closure without PVD may rarely occur in patients with LHEP. The surgical removal of ILM and LHEP may contribute to the successful macular hole closure after vitrectomy.

This prospective, open-label, single-arm, non-randomized clinical trial, assessed the efficacy of a 2-year treat-and-extend (T&E) regimen involving intravitreal aflibercept injection (IAI), with the longest treatment interval set to 16 weeks, and adjunct focal/grid laser in diabetic macula edema (DME) patients. We examined 40 eyes (40 adults) with fovea-involving DME from 8 Japanese centers between April 2015 and February 2017. Participants received IAI with an induction period featuring monthly injections and a subsequent T&E period featuring 8–16-week injection interval, adjusted based on optical coherence tomography findings. The primary endpoints were mean changes in the best-corrected visual acuity (BCVA) and central subfield macular thickness (CST) from baseline. Thirty patients (75%) completed the 2-year follow-up. The mean BCVA and CST changed from 60.5 ± 15.6 letters and 499.2 ± 105.6 µm at baseline to 66.6 ± 17.1 letters (P = 0.217) and 315.2 ± 79.0 µm (P

We retrospectively compared the stability of intraocular lenses (IOLs) routinely used at our institution by measuring IOL position after phacovitrectomy for rhegmatogenous retinal detachment (RRD). Patients with RRD who underwent phacovitrectomy with gas tamponade received one of three IOLs: 6-mm, single-piece NS-60YG (NIDEK, 15 eyes); 6-mm, single-piece XY1 (HOYA, 11 eyes); or 7-mm, three-piece X-70 (Santen, 11 eyes). Various parameters associated with the anterior chamber, lens, and IOL were measured by swept-source anterior segment optical coherence tomography (CASIA2; Tomey Corp) before and 1 week and 1 month after surgery. IOL position was determined as follows: IOL position = (postoperative aqueous depth [AQD] − preoperative AQD)/lens thickness. We found no significant difference in axial length between the IOLs (p = 0.97). At 1 week, IOL position was as follows: NS-60YG, 0.32; XY1, 0.24; and X-70, 0.26 (p < 0.05). The respective IOL positions at 1 month were 0.35, 0.27, and 0.28 (p < 0.01). These results indicated the smallest anterior shift with NS-60YG. To replicate the anterior shift of IOL position ex vivo, biomechanical measurement was performed. NS-60YG resisted more displacement force than the other IOLs. Thus, in eyes undergoing phacovitrectomy for RRD, NS-60YG was the most stable of the three IOLs studied.

We investigated the effect of tofogliflozin, a sodium-dependent glucose cotransporter 2 inhibitor (SGLT2i), on retinal blood flow dysregulation, neural retinal dysfunction, and the impaired neurovascular coupling in type 2 diabetic mice. Tofogliflozin was added to mouse chow to deliver 5 mg/kg/day and 6-week-old mice were fed for 8 weeks. The longitudinal changes in the retinal neuronal function and blood flow responses to systemic hyperoxia and flicker stimulation were evaluated every 2 weeks in diabetic db/db mice that received tofogliflozin (n =6) or placebo (n = 6) from 8 to 14 weeks of age. We also evaluated glial activation and vascular endothelial growth factor (VEGF) expression by immunofluorescence. Tofogliflozin treatment caused a sustained decrease in blood glucose in db/db mice from 8 weeks of the treatment. In tofogliflozin-treated db/db mice, both responses improved from 8 to 14 weeks of age, compared with vehicle-treated diabetic mice. Subsequently, the electroretinography implicit time for the oscillatory potential was significantly improved in SGLT2i-treated db/db mice. The systemic tofogliflozin treatment prevented the activation of glial fibrillary acidic protein and VEGF protein expression, as detected by immunofluorescence. Our results suggest that glycemic control with tofogliflozin significantly improved the impaired retinal neurovascular coupling in type 2 diabetic mice with the inhibition of retinal glial activation.

We investigated the effect of fenofibrate nano-eyedrops (FenoNano) on impaired retinal blood flow regulation in type 2 diabetic mice. Six-week-old db/db mice were randomly divided into an untreated group (n = 6) and treated group, which received FenoNano (n = 6). The longitudinal changes in retinal neuronal function and blood flow responses to systemic hyperoxia and flicker stimulation were evaluated every 2 weeks in diabetic db/db mice treated with FenoNano (n = 6) or the vehicle (n = 6) from ages 8–14 weeks. The retinal blood flow was assessed using laser speckle flowgraphy. We also evaluated the expressions of vascular endothelial growth factor (VEGF), glial fibrillary acidic protein (GFAP), and aquaporin 4 (AQP4) and the phosphorylation of peroxisome proliferator-activated receptor alpha (PPAR-α) by immunofluorescence. In db/db mice treated with FenoNano, both responses were restored from 8 to 14 weeks of age compared with the diabetic mice treated with the vehicle. At 14 weeks of age, the impaired regulation of retinal blood flow during systemic hyperoxia and flicker stimulation improved to about half of that in the db/db mice treated with FenoNano compared with the db/m control group (n = 5). FenoNano prevented the activation of VEGF and GFAP expression and increased the AQP4 expression and the phosphorylation of PPAR-α detected by immunofluorescence compared with the diabetic mice treated with the vehicle eyedrop. Our results suggested that the fenofibrate nano-eyedrops prevent retinal glial dysfunction via the phosphorylation of PPAR-α and improves the retinal blood flow dysregulation in type 2 diabetic mice.

Many studies have demonstrated that rhegmatogenous retinal detachment (RRD) leads to impaired retinal circulation. However, the involvement of inflammation in the RRD-induced worsening of retinal circulation was obscure. This retrospective observational study included 150 patients with primary RRD (macula-on, n = 63; macula-off, n = 87) who underwent 25-gauge microincision vitrectomy surgery (25G MIVS). Total retinal blood flow was represented by the mean blur rate (MBR) of the optic nerve head vessel, measured by laser speckle flowgraphy preoperatively and until 6 months postoperatively. Aqueous humor samples were obtained during surgery to determine cytokine concentrations by enzyme-linked immunosorbent assay. At 3 and 6 months postoperatively, there were no significant differences between eyes with macula-on RRD and fellow eyes. However, in macula-off RRD, MBR remained significantly lower in RRD eyes 6 months postoperatively (P r = − 0.47, P = 0.01) in macula-on, but not macula-off, RRD. Six months postoperatively, r-MBR correlated significantly with sICAM-1 levels (r = − 0.36, P = 0.02) in macula-off RRD. ICAM-1 may play a role in RRD-induced deterioration of retinal circulation.

We developed a new method to retrieve a dropped nucleus of the lens via a small incision using bipolar pencils, the kebab technique, to solve the lack of small-gauge fragmatomes, and the expense and toxicity of perfluorocarbon liquids (PFCL). A total of 8 eyes in 6 patients underwent this technique and were reviewed. After vitrectomy, the dropped nucleus of the lens was lifted from the retina by adhesion with a bipolar pencil, and phacoemulsification was performed while rotating the lens. The outcome measures were best-corrected visual acuity (BCVA), intraocular pressure (IOP), and corneal endothelial cell density before and after surgery. Surgical indications included zonular weakness, trauma, acute angle closure attack, and phacolytic glaucoma. At 1 month, BCVA improved from a mean (standard deviation, SD) 1.67 logMAR (0.90) to 1.14 logMAR (1.01). The mean preoperative IOP was 24.5 (16.8) mmHg and postoperative IOP was 11.0 (2.8) mmHg. The mean preoperative corneal endothelial cell count was 2600 (322) cells/mm2 (one eye was unmeasurable) and postoperative corneal endothelial cell count was 2387 (431) cells/mm2. There were no postoperative complications. The retrieval of a dropped nucleus of the lens using a bipolar pencil enables small incisions without using PFCL.

Purpose To report the changes over time in ocular blood flow quantified by laser speckle flowgraphy (LSFG) in a treated large retinal arterial macroaneurysm (RAM). Observations A 72-year old female presented with sudden decreased vision in the left eye. Fundus examination revealed a RAM and vitreous hemorrhage (VH), which worsened over one month. A vitrectomy was performed to remove the VH, with 20% sulfur hexafluoride injected into the vitreous cavity. The VH recurred two weeks later and the RAM was found to have enlarged from one-quarter disc diameter (DD) to three DDs during a second vitrectomy. The RAM subsequently shrunk spontaneously to one DD without recurrent VH during the following 2 weeks. Beginning 4 weeks after the second vitrectomy we performed serial LSFG examinations of the RAM and found that the mean blur rate (MBR) of the RAM and retinal flow volume (RFV) in both the feeding arteriole and draining venule decreased as the RAM continued to involute. Conclusions and importance MBR and arteriolar and venular RFV measured by LSFG decreased with RAM involution. Longitudinal followup of blood flow by LSFG may be useful for noninvasive evaluation of the stability of RAMs.

We developed a new method to retrieve a dropped nucleus via a small incision using bipolar pencils, the kebab technique, to solve the lack of small-gauge fragmatomes, and the expense and toxicity of perfluorocarbon liquids (PFCL). A total of 8 eyes in 6 patients underwent this technique and were reviewed. After vitrectomy, the dropped nucleus was lifted from the retina by adhesion with a bipolar pencil, and phacoemulsification was performed while rotating the lens. The outcome measures were best-corrected visual acuity (BCVA), intraocular pressure (IOP), and corneal endothelial cell density before and after surgery. Surgical indications included zonular weakness, trauma, acute angle closure attack, and phacolytic glaucoma. At 1 month, BCVA improved from a mean ± SD 1.67 logMAR (± 0.90) to 1.14 logMAR (± 1.01). The mean preoperative intraocular pressure (IOP) was 24.5 (± 16.8) mmHg and postoperative IOP was 11.0 (± 2.8) mmHg. The mean preoperative corneal endothelial cell count was 2600 (322) cells/mm2 (one eye was unmeasurable) and postoperative corneal endothelial cell count was 2387 (± 431) cells/ mm2. There were no postoperative complications. The retrieval of a dropped nucleus using a bipolar pencil enables small incisions without using PFCL.

This study aimed to evaluate longitudinal changes in retinal blood flow in response to flicker stimulation and systemic hyperoxia in mice using a laser speckle flowgraphy (LSFG-Micro). The retinal blood flow in vascular area surrounding the optic nerve head was measured in 8-week-old male mice every 2 weeks until age 20-week. The coefficient of variation of retinal blood flow under resting condition was analyzed every 2 weeks to validate the consistency of the measurement. On day 1 of the experiment, retinal blood flow was assessed every 20 s for 6 min during and after 3 min flicker light (12 Hz) stimulation; on day 2, retinal blood flow was measured every minute for 20 min during and after 10 min systemic hyperoxia; and on day 3, electroretinography (ERG) was performed. Body weight, systemic blood pressure, and ocular perfusion pressure increased significantly with age, but the resting retinal blood flow and ERG parameters remained unchanged. Retinal blood flow significantly increased with flicker stimulation and decreased with systemic hyperoxia, independent of age. The LSFG-Micro provides consistent and reproducible retinal blood flow measurement in adult mice. Longitudinal assessments of retinal blood flow in response to flicker stimulation and systemic hyperoxia may be useful indexes for noninvasive monitoring of vascular function in retinas.

To investigate the efficacy and safety of a treat-and-extend (T&E) regimen using aflibercept (Eylea) for diabetic macular edema (DME). Prospective, open-label, multicenter, single-arm, nonblinded clinical study. Forty eyes of 40 patients with DME received a T&E regimen of intravitreal aflibercept injection (IAI) with the longest treatment interval set to 16 weeks and adjunct focal/grid laser for 1 year. An intent-to-treat analysis was performed using the same last-observation-carried-forward method. A per-protocol analysis was also performed for patients who completed a 1-year T&E regimen. The primary endpoints were mean changes in best-corrected visual acuity (BCVA) and central subfield macular thickness (CST) from baseline. Secondary endpoints included IAI-interval extension and resultant IAI numbers and the association between an early response to IAI and final BCVA gain at 1 year. Thirty-one patients (77.5%) completed the 1-year aflibercept T&E regimen. In these per-protocol participants, the mean CST improvement/reduction was 187.3 ± 145.0 µm (P

Background: Pro re nata (PRN) regimen using anti-vascular endothelial growth factor (VEGF) agent is popular for the treatment of diabetic macular edema (DME). We investigated the influence of waiting time (WT) and interval between the date of recurrence of edema and re-injection on treatment efficacy. Methods: This retrospective study conducted at 7 sites in Japan enrolled patients who received intravitreal injection of ranibizumab (IVR) and aflibercept (IVA) in 1+PRN regimen. Enrolled patients were divided into 2 groups: prompt group (less than 1 week) and deferred group (3 weeks or more). Central retinal thickness (CRT) and best corrected visual acuity (BCVA) were measured every month for 1 year. Results: CRT in the deferred group was significantly higher than that in the prompt group at 2, 5, 6, 7, and 12 months (p < 0.05). BCVA in the prompt group was significantly better than that in the deferred group at 7, 10, and 12 months (p < 0.05). Conclusion: The prompt group was superior in anatomical and functional improvement of DME in anti-VEGF therapy than the deferred group. Our data suggests that shorter WT is recommended for better visual prognosis in the treatment for DME.

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), Laser speckle flowgraphy (LSFG) is an ophthalmologic equipment that qualitatively detects the blood flow of the optic nerve head, which is known to be related with cerebral microcirculation. LSFG can also measure the mean blur rate, which quantitatively calculates the blood flow. We aimed to assess the utility of LSFG in the evaluation of cerebral perfusion during aortic surgery under hypothermic circulatory arrest with retrograde and antegrade cerebral perfusion. Two patients underwent total arch replacement for aneurysm. The blood flow of the optic nerve head was monitored with LSFG and the mean blur rate value was measured during the surgery. The LSFG could detect the blood flow quantitatively in the optic nerve head during both retrograde and antegrade cerebral perfusion; and the value was correlated with rSO2 value.

The effect of combination therapy using intravitreal ranibizumab (IVR) injections and short pulse focal/grid laser photocoagulation was evaluated for the treatment of diabetic macular edema (DME). The current investigation was a preliminary single-arm, open-label, prospective clinical study conducted on 21 eyes at 4 sites in Japan. Treatment protocol consisted of two phases. The induction IVR phase included two monthly IVRs followed by PRN IVR phase in which additional IVR was administered if the central macular thickness (CMT) exceeded 300 μm. One week after each IVR in both phases, short pulse focal/grid laser was delivered to treat residual leakage outside of the fovea (>500 μm) and reduce edema fluid influx. At the 6-month endpoint, the effects of treatment were examined in terms of best corrected visual acuity (BCVA), CMT, and required number of IVR injections in eyes with or without perifoveal leaking microaneurysms (MAs). In eyes with initial BCVA ≤70 letters, mean BCVA was significantly ameliorated by 7.0 ± 7.4 letters (P = 0.0324) and mean CMT improved significantly by 174.8 ± 105.0 µm (P = 0.0005). Both BCVA improvement (P = 0.8693) and CMT reduction (P = 0.9336) were comparable between MA(−) and MA(+) groups. The MA(−) group required significantly fewer PRN-IVR injections than did the MA(+) group over the 6-month study period (mean 3.4 ± 1.6 vs. 5.3 ± 0.9, median 3.0 vs. 5.5; P = 0.0229). Short pulse focal/grid laser photocoagulation could reduce the number of IVR injections required to resolve macular edema and increase BCVA in a possible mechanism of reduced influx of edema fluid into the foveal area in eyes without apparent perifoveal microaneurysms.

Purpose To report the detailed macular morphology documented by spectral-domain optical coherence tomography (SD-OCT) in a patient with retinitis pigmentosa (RP) and diabetic retinopathy (DR). Observations A 54-year-old man with a hemoglobin A1c level of 11.4% was referred for decreased visual acuity (VA) bilaterally (right eye, 20/100; left eye, 20/40). Funduscopy showed typical retinal findings of RP bilaterally. The macular area of both fundi showed retinal dot-and-blot hemorrhages, hard exudates. Time-domain OCT revealed macular edema in the right eye. The patient was diagnosed with RP accompanied by DR bilaterally. Five years after the first visit, the BCVAs remained 20/100 in the right eye and 20/40 in the left eye. SD-OCT showed that the retinas were thinner temporal to the maculas. The external limiting membrane line (ELM) and the ellipsoid zone of the photoreceptors line (EZ) was not visible in the foveal region in the right eye and temporal to the macula in both eyes. The image revealed the characteristic intraretinal and intrachoroidal hyrerreflective foci, the number of which increased corresponding to the extent of the disappearance of the ELM and EZ line with thinning of the outer nuclear layer (ONL). In addition, the image also showed a great number of the hyperreflective foci in the ONL and the choriocapillaris in the foveal region in the right eye compared with the left eye. Conclusions In the current case, the SD-OCT findings suggested that the characteristic hyrerreflective foci clinically observed in the fundi of a patient with RP accompanied by DR are present in the retinal layers and the choroid. In addition, the foci in the retinal and choroidal layers in the foveal region may increase as vision declines corresponding to the disappearance of the ELM and EZ line.

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License., PURPOSE: Although endothelium-dependent nitric oxide (NO)-mediated dilation of retinal arterioles has been well described, the role of endothelium-derived hyperpolarizing factor (EDHF) in the retinal arteriolar response remains unclear. In the current study, we examined the contribution of EDHF to the retinal arteriolar dilation to the inflammatory agent histamine and investigated the signaling mechanisms underlying this vasomotor activity. METHODS: Porcine retinal arterioles were isolated, cannulated, and pressurized without flow for functional study by using video microscopic techniques. The immunohistochemical staining was performed to determine histamine receptor subtypes. RESULTS: Histamine (0.1-30 μM) produced concentration-dependent dilation of retinal arterioles in a manner sensitive to H1- and H2-receptor antagonists chlorpheniramine and famotidine, respectively. Histamine-induced vasodilation was almost abolished after endothelial removal. In the intact vessels, vasodilation to histamine was partially inhibited by the inhibitors of cyclooxygenase (indomethacin), NO synthase (NG-nitro-L-arginine methyl ester, L-NAME), or Ca2+ -activated K+ (KCa) channels (apamin plus charybdotoxin). Combination of the above inhibitors abolished histamine-induced vasodilation. Residual vasodilation in the presence of indomethacin and L-NAME was further reduced by the cytochrome P450 enzyme inhibitor sulfaphenazole but not by the gap junction inhibitor carbenoxolone or the hydrogen peroxide scavenger catalase. Immunohistochemical signals for H1- and H2-receptor expression were found only in the endothelium. CONCLUSIONS: The endothelium plays an essential role in the dilation of porcine retinal arterioles to histamine via H1- and H2-receptor activation. The EDHF derived from cytochrome P450 contributed in part to this vasodilation via KCa channel activation, in addition to the endothelial release of NO and prostanoids.

PURPOSE: To examine the long-term effects of cigarette smoking on retinal circulation in patients with type 2 diabetes. METHODS: Seventy-four patients with type 2 diabetes mellitus and minimal (no or mild nonproliferative) diabetic retinopathy (DR) were evaluated. These patients with type 2 diabetes were divided into three groups based on their smoking history: current smokers (n = 19), past smokers (n = 20), and never smoked (n = 35). The retinal circulatory parameters were measured with laser Doppler velocimetry and were compared among the groups. RESULTS: There were significant decreases in the retinal blood flow (RBF; 8.9 ± 2.9 vs. 11.6 ± 3.1 μL/min, P = 0.009) with decreased blood velocity (V; 29.6 ± 6.8 vs. 37.8 ± 9.0 mm/s, P = 0.003) but no difference in the vessel diameter (D; 112.0 ± 11.9 vs. 113.7 ± 8.6 μm, P = 0.57) in the current smokers compared with those who never smoked. There were no differences in the RBF, blood V, and vessel D in the past smokers compared with those who never smoked and current smokers. Multiple regression analysis showed that the creatinine level was correlated negatively with the RBF and that current smoking was significantly and independent correlated with decreased RBF. CONCLUSIONS: Our results indicated that the blood V and RBF in the retinal arterioles may decrease in patients with type 2 diabetes who are chronic smokers, suggesting that chronic smoking may be associated with decreased RBF, probably via lower blood V in the retinal arterioles in early-phase DR.

PURPOSE To report the detailed changes in the macular morphology documented by spectral domain optical coherence tomography in a 74-year-old woman with macular hole (MH) formation after vitreomacular detachment with an operculum. METHODS History and clinical examinations included slit-lamp biomicroscopy, best-corrected visual acuity, color fundus photography, and spectral domain optical coherence tomography. RESULTS The patient was referred for decreased vision in the left eye (visual acuity, right eye, 20/20; left eye, 20/50). Spectral domain optical coherence tomography showed a full-thickness MH in the left eye. The right eye had a lamellar MH, and the photoreceptor inner/outer segment line was uninterrupted beneath the central fovea. The right eye had vitreomacular detachment with a small round operculum suggestive of an elevated inner foveal retina. Thirty-seven months after the initial visit, the patient returned with visual acuity in the right eye that had decreased to 20/50 and a full-thickness MH had developed in the presence of vitreomacular detachment. An epiretinal membrane appeared nasal to the fovea, and the macular surface had a triangular dimple beneath the membrane. A large retinal schisis developed nasal to the hole. A tightrope-like structure bridged the MH edges. CONCLUSION In this case, the MH resulted from the tangential traction caused by the epiretinal membrane after vitreomacular detachment developed; the MH was accompanied by a small round operculum, a retinal dimple beneath the membrane, and a tightrope-like structure that bridged the hole edges. The operculum likely comprised a detached inner foveal retina alone and did not include retinal photoreceptor cells.

PURPOSE To report a case of retinal cavernous hemangioma documented by spectral domain optical coherence tomography and retro-mode retinal imaging by confocal scanning laser ophthalmoscope. METHODS Clinical examination, fluorescein angiography, spectral domain optical coherence tomography, and scanning laser ophthalmoscope retro-mode imaging were performed. RESULTS Fundus examination of the left eye of an asymptomatic 39-year-old woman showed an irregularly elevated dark red lesion with a cluster of various-sized saccular aneurysms. The retinal cavernous hemangioma lesions were in the upper vascular arcade. A late-phase fluorescein angiography image showed a typical finding, known as fluorescence capping, characterized by incomplete perfusion because of plasma-erythrocyte separation, which was seen in some larger aneurysms. Spectral domain optical coherence tomography showed that various-sized dilated cystic spaces corresponded to the aneurysms. The image showed the horizontal line, which corresponded to the fluorescence capping in some larger aneurysms. Scanning laser ophthalmoscope retro-mode images showed the individual sizes and septum of the aneurysms. The image also showed the characteristic dots-and-lines pattern around the retinal cavernous hemangioma at the corresponding area of inner retinoschisis attributed to the aneurysms without outer retinoschisis on the spectral domain optical coherence tomography images. CONCLUSION Spectral domain optical coherence tomography and scanning laser ophthalmoscope retro-mode imaging may be useful for evaluating the pathophysiologic features and the full extent of the retinal cavernous hemangioma.

Purpose To evaluate the retinal microcirculation using a segmental-scanning Doppler optical coherence tomography (DOCT) flowmeter in a patient with Takayasu's arteritis (TA) with aortic valve regurgitation (AR). Observations We measured the retinal blood velocity (V), retinal blood flow (RBF), and retinal blood velocity profiles (RBVP) of the major retinal arterioles using a DOCT flowmeter. The arteries were measured at the straight portion 1 disc diameter from the optic disc. Horizontal velocity profiles were extracted to evaluate the RBVP during one cardiac cycle. A patient with TA with stage 2 Takayasu retinopathy (TR) and AR, had normal RBF and V, and the RBVP had a parabolic pattern in the systolic phase. However, the V was very slow and the RBVP had an abnormal pattern in the diastolic phase. Conclusions and importance The current study showed for the first time that segmental-scanning DOCT flowmeter enables evaluation of an abnormal flow pattern of the RVBP in the retinal arterioles in a patient with TA and AR. Measurement of the retinal arterial blood flow may detect aortic valve dysfunction and shed light on the pathogenesis of TR.

IntroductionPancreatic duodenum homeobox 1 (Pdx1) expression is crucial for pancreatic organogenesis and is a key regulator of insulin gene expression. Hairy and enhancer of split 1 (Hes1) controls tissue morphogenesis by maintaining undifferentiated cells.Hes1encodes a basic helix loop helix (bHLH) transcriptional repressor and functionally antagonizes positive bHLH genes, such as the endocrine determination gene neurogenin-3. Here, we generated a new pig model for diabetes by genetic engineeringPdx1andHes1genes.Research design and methodsA transgenic (Tg) chimera pig with germ cells carrying a construct expressingHes1under the control of thePdx1promoter was used to mate with wild-type gilts to obtain Tg piglets.ResultsThe Tg pigs showed perinatal death; however, this phenotype could be rescued by insulin treatment. The duodenal and splenic lobes of the Tg pigs were slender and did not fully develop, whereas the connective lobe was absent. β cells were not detected, even in the adult pancreas, although other endocrine cells were detected, and exocrine cells functioned normally. The pigs showed no irregularities in any organs, except diabetes-associated pathological alterations, such as retinopathy and renal damage.ConclusionPdx1-Hes1Tg pigs were an attractive model for the analysis of pancreatic development and testing of novel treatment strategies for diabetes.

Purpose: Evaluate the effect of foveal leaking microaneurysms (MAs) on the required number of intravitreal ranibiz­umab (IVR) injections in the treatment of center-involving diabetic macular edema (DME) when treated with focal/grid laser. Design: A pilot study of prospective, nonrandomized, multicenter clinical trial. Methods: This study enrolled 21 eyes with DME for which pro re nata IVR injections were combined with short-pulse focal/grid laser. At 12 months, best-corrected visual acuity (BCVA), central subfield macular thickness (CMT), and the required number of IVRs to maintain CMT < 300 µm were compared between eyes with or without foveal leaking MAs, termed the MA(+) and MA(–) groups, respectively. Results: Significant CMT improvements (p < 0.0001) and increased BCVA of 4.0 ± 8.5 letters were observed at 12 months. The MA(–) group required significantly fewer IVRs than did the MA(+) group (mean: 4.9 ± 3.0 vs. 8.6 ± 3.0; p = 0.0306). In the latter 6 months of the 1-year follow-up, 50% (4/8) of MA(–) eyes did not require any IVR administration to sustain CMT < 300 µm. Conclusions: A combination therapy of short-pulse focal/grid laser and reduced IVR injections appeared noninferior to previous reports of IVR monotherapy. Further large-scale investigations are warranted.

Purpose To evaluate how the growth of neovascularization elsewhere (NVE) was delineated in an eye with hemicentral retinal vein occlusion (CRVO) using optical coherence tomography (OCT) angiography. Patients and methods We examined a 64-year-old man diagnosed with hemi-CRVO. The area around the occluded vein was scanned using a spectral-domain OCT device (RTVue XR Avanti). Blood flow was detected using the split-spectrum amplitude-decorrelation angiography (SSADA) algorithm. Color fundus photography, fluorescein angiography (FA), and OCT angiography examinations were performed at the first visit and at 3 and 6 months postpresentation. Results At the first visit, FA revealed delayed retinal venous filling and extensive areas of capillary nonperfusion. The patient underwent a trial of intravitreal ranibizumab injection (0.5 mg/0.05 mL) for the treatment of macular edema. At 3 months postpresentation, there was no NVE around the occluded vein in the en-face SSADA image, but at 6 months, NVE appeared on the occluded veins. The en-face SSADA image showed the NVE structure in the fibrovascular membrane on the occluded vein more clearly than FA images. Conclusion OCT angiography clearly visualized the sprouting of NVE in an eye with hemi-CRVO. New findings of the vascular structure of NVE in hemi-CRVO were revealed using the en-face SSADA algorithm.

Purpose: To clarify the area of retinoschisis by X-linked juvenile retinoschisis (XLRS) using swept-source optical coherence tomography (SS-OCT) en face images. Observations: We report two cases of XLRS in the same family. The patients presented with bilateral blurred vision. The posterior segment examination showed a spoked-wheel pattern in the macula. SS-OCT cross-sectional images revealed widespread retinal splitting at the level of the inner nuclear layer bilaterally. We diagnosed XLRS. To evaluate the area of retinoschisis, we obtained en face SS-OCT images, which clearly visualized the area of retinoschisis seen as a sunflower-like structure in the macula. Conclusion and Importance: We report the findings on en face SS-OCT images from patients with XLRS. The en face images using SS-OCT showed the precise area of retinoschisis compared with the SS-OCT thickness map and are useful for managing patients with XLRS.

The purpose of this study was to investigate the effects of aging on anteroposterior tortuosity of the retinal vein at the arteriovenous (AV) crossing in healthy subjects.We examined 48 eyes of 24 healthy older Japanese subjects (60 years), and, as controls, 42 eyes of 21 healthy younger Japanese subjects (30 years). Retinal vein images at the AV crossing were obtained by optical coherence tomography. The depth of the vein was measured vertically from the outer border of the retinal pigment epithelium to the outer vein wall. We defined "m" as the deepest point of the vein at the AV crossing and "M" as the shallowest point. To evaluate the anteroposterior tortuosity of the retinal vein, we calculated the ratio m/M.Mean m, M, and m/M in older subjects were 76.5 ± 13.1 µm, 142.7 ± 21.2 µm, and 0.52 ± 0.09, respectively. In younger control subjects, the values were 64.1 ± 12.6 µm, 139.9 ± 22.4 µm, and 0.46 ± 0.06. The values of "M" were not significantly different between groups, whereas both "m/M" and "m" were significantly (p = 0.021) lower in the older subjects than in the younger subjects.Anteroposterior tortuosity of the retinal vein was evaluated based on the maximum and minimum retinal vein depth measurements at the AV crossing using optical coherence tomography. Anteroposterior tortuosity of the retinal vein at the AV crossing is increased with age.

Introduction: To determine if the serum prorenin level is useful for detecting ocular disease in a non-diabetic population. Materials and methods: We enrolled non-diabetic men ( n = 402) and women ( n = 349) in our study. We used the antibody-activating direct enzyme kinetic assay of human prorenin to determine serum prorenin levels. We performed multiple regression analysis to determine the factors that affect serum prorenin levels, such as: age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol, fasting blood sugar, and HbA1c or estimated glomerular filtration rate. Our study subjects were divided into groups by their ophthalmologic diagnosis. One-way analysis of variance (ANOVA) was performed to detect a significant difference in the serum prorenin levels among the groups. Results: There were no significant differences in serum prorenin levels among the ocular diseases and disorders. The DBP was negatively correlated with serum prorenin levels in men ( r = − 0.1992; p = 0.021) and in women ( r = − 0.2067; p = 0.031). Conclusion: Considering the current results and those of previous studies together, we found that the prorenin value is useful solely for predicting development of diabetic retinopathy in adults.