Long-term observation of the vitreomacular relationship in normal fellow eyes of patients with unilateral idiopathic macular holes.

PURPOSE: To describe long-term changes in the vitreomacular relationship in normal fellow eyes of patients with unilateral idiopathic macular holes (MHs). METHODS: This is a retrospective, observational case series. The medical records of patients who underwent surgery for idiopathic MHs between May 2000 and December 2010 were reviewed. Patients who had clinically normal fellow eyes and underwent 12 months or more of follow-up were included. The vitreomacular relationship in the fellow eyes was evaluated using optical coherence tomography (OCT) and slit-lamp biomicroscopy. RESULTS: The study included 153 patients with a mean age of 65.5 years and a mean follow-up of 33.5 months (range, 12-121). The incidence of vitreomacular attachments evaluated by OCT was 52% (80 eyes) at initial examination, which decreased to 41, 37 and 23% at 1, 2 and 3 years after the initial examination, respectively. Of the 80 eyes with vitreomacular attachments at initial examination, 40 (50%) still had vitreomacular attachments at the final visit. Of the remaining 40 eyes in which vitreomacular separation occurred during follow-up, 11 (28%) developed an MH, with a mean interval of 45 months. None of the eyes with vitreomacular separation at presentation developed an MH. CONCLUSION: This largest series of fellow eyes of MHs followed by OCT shows that, at presentation, about half of the patients already have premacular vitreous detachment and therefore no risk of MH, and that second MH develops in about 30% in the process of vitreomacular separation, which evolves over a prolonged period.

Vitreomacular interface and outer foveal microstructure in fellow eyes of patients with unilateral macular holes.

PURPOSE: To investigate the relationship between the vitreomacular interface and the integrity of the photoreceptor microstructures in the normal fellow eyes of patients with unilateral macular holes. METHODS: Retrospective observational case series. Fifty-five normal fellow eyes of 55 patients with unilateral macular holes were enrolled in the study. All patients underwent complete ophthalmologic examination including best-corrected visual acuity, slit-lamp biomicroscopy, fundus photography, and spectral domain optical coherence tomography at initial and follow-up visits. The features of the vitreomacular interface were graded based on spectral domain optical coherence tomography findings. RESULTS: At the initial visit, 28 of 55 eyes (51%) had vitreomacular attachments with or without perifoveal posterior vitreous detachment. On their initial visit, a triangular elevation of the cone outer segment tips line was identified in 11 of 18 eyes (61%) with perifoveal posterior vitreous detachment across all quadrants with persistent attachment to the fovea. Conversely, none of the remaining 37 eyes with the other stages of posterior vitreous detachment showed any abnormalities. Over a mean follow-up period of 18 months (range, 12-24 months), the elevation of the cone outer segment tips line resolved after spontaneous vitreomacular separation without macular holes in 3 eyes, remained unchanged in 6 eyes, and showed progression to a full-thickness macular hole in 2 eyes. CONCLUSION: These findings suggest that an elevation of the cone outer segment tips line in the normal fellow eyes of patients with macular holes is caused by the focal traction of the vitreous at the foveal center. This is considered to be an important primary change observed in the macular tissue in full-thickness macular hole formation.

Cilostazol ameliorates systemic insulin resistance in diabetic db/db mice by suppressing chronic inflammation in adipose tissue via modulation of both adipocyte and macrophage functions.

Cilostazol, an inhibitor of phosphodiesterase 3B, is widely used as an anti-platelet drug in diabetic patients. Recently, cilostazol has been shown to promote preadipocyte differentiation to mature adipocyte and affect glucose homeostasis; therefore, we examined the impact of cilostazol on impaired glucose metabolism in adipose tissues of diabetic db/db mice. Administration of cilostazol at 100-300 mg/kg/day significantly improved glucose tolerance and insulin sensitivity in a dose-dependent manner in db/db mice, whereas these effects were not observed in non-diabetic control mice. Cilostazol reduced the adipocyte size and suppressed mRNA expressions of monocyte chemoattractant protein 1, CD11c, and tumor necrosis factor α (TNFα) in the epididymal fat tissue of db/db mice. As for the cellular mechanism, cilostazol attenuated lipopolysaccharide (LPS)-induced TNFα expression by decreasing the mRNA and protein levels of Toll-like receptor 4 in Raw264.3 macrophages. Cilostazol also effectively ameliorated the TNFα-induced decrease of insulin-stimulated Akt phosphorylation and [(3)H]2-deoxyglucose uptake by suppressing c-Jun N terminal kinase-mediated serine phosphorylation of insulin receptor substrate 1 in 3T3-L1 adipocytes. Importantly, the improvement of impaired insulin signaling was blunted by pretreatment with KT5720, a protein kinase A inhibitor, but not with GW9662, a peroxisome proliferator-activated receptor γ. These results indicate that cilostazol suppressed TNFα production from macrophages and attenuated TNFα-induced chronic inflammation in adipose tissue, leading to the improvement of glucose intolerance and insulin resistance in obese diabetic mice. Thus, the present study reveals an additional benefit in the use of cilostazol in the treatment of patients with type 2 diabetes.

Atypical presentation of acute macular neuroretinopathy with tiny parafoveal reddish-brown lesions.

PURPOSE: To report two cases of acute macular neuroretinopathy with unusually small parafoveal lesions, which showed later recurrent lesions either in the same eye or the fellow eye. METHODS: Observational case series. PATIENTS: In case 1, a 48-year-old woman developed a sudden onset of a tiny paracentral scotoma associated with a small reddish-brown paracentral lesion. A new paracentral lesion with a corresponding scotoma developed 1 year later. In case 2, a 39-year-old man with diabetes type 1 developed a paracentral scotoma OS with a corresponding small reddish-brown lesion. Two months later, a similar lesion with a corresponding scotoma developed in the fellow eye. CONCLUSIONS: Acute macular neuroretinopathy may present with tiny paracentral lesions difficult to detect with fundus examination, and may be associated with recurrent lesions either in the same eye or the fellow eye.

Incidence of iatrogenic peripheral retinal breaks in 23-gauge vitrectomy for macular diseases.

PURPOSE: To assess the incidence of iatrogenic peripheral retinal breaks in 23-gauge vitrectomy for macular diseases and to compare it with 20-gauge vitrectomy. METHODS: Retrospective, comparative, interventional case series. We compared the incidence of iatrogenic peripheral retinal breaks in 176 eyes undergoing 23-gauge vitrectomy between January 2007 and November 2009 (23-gauge group) and 153 eyes undergoing 20-gauge vitrectomy between January 2004 and June 2006 (20-gauge group) for either idiopathic macular holes or idiopathic epiretinal membranes. All surgeries were performed by one surgeon at a single hospital. Main outcome measure was the incidence rate of iatrogenic peripheral retinal breaks discovered intraoperatively and postoperatively. RESULTS: Iatrogenic peripheral retinal breaks occurred in 1 eye in the 23-gauge group and in 11 eyes in the 20-gauge group during surgery. Additional iatrogenic retinal breaks were found in 1 eye in the 23-gauge group and in 2 eyes in the 20-gauge group within 1 month after surgery. The overall incidence of iatrogenic peripheral retinal breaks was 1.1% (2 of 176) in the 23-gauge group and 8.5% (13 of 153) in the 20-gauge group. The difference was statistically significant (P = 0.0023). CONCLUSION: The incidence of iatrogenic peripheral retinal breaks during vitrectomy for macular diseases is significantly lower in 23-gauge vitrectomy than in 20-gauge vitrectomy.

Both type I and II IFN induce insulin resistance by inducing different isoforms of SOCS expression in 3T3-L1 adipocytes.

Although elevation of the blood glucose level is a causal adverse effect of treatment with interferon (IFN), the precise underlying molecular mechanism is largely unknown. We examined the effects of type I and type II IFN (IFN-ß and IFN-γ) on insulin-induced metabolic signaling leading to glucose uptake in 3T3-L1 adipocytes. IFN-ß suppressed insulin-induced tyrosine phosphorylation of IRS-1 without affecting its expression, whereas IFN-γ reduced both the protein level and tyrosine phosphorylation. Although both IFNs stimulated phosphorylation of STAT1 (at Tyr(701)) and STAT3 (at Tyr(705)) after treatment for 30 min, subsequent properties of induction of the SOCS isoform were different. IFN-ß preferentially induced SOCS1 rather than SOCS3, whereas IFN-γ strongly induced SOCS3 expression alone. In addition, adenovirus-mediated overexpression of either SOCS1 or SOCS3 inhibited insulin-induced tyrosine phosphorylation of IRS-1, whereas the reduction of IRS-1 protein was observed only in SOCS3-expressed cells. Notably, IFN-ß-induced SOCS1 expression and suppression of insulin-induced tyrosine phosphorylation of IRS-1 were attenuated by siRNA-mediated knockdown of STAT1. In contrast, adenovirus-mediated expression of a dominant-negative STAT3 (F-STAT3) attenuated IFN-γ-induced SOCS3 expression, reduction of IRS-1 protein, and suppression of insulin-induced glucose uptake but did not have any effect on the IFN-ß-mediated SOCS1 expression and inhibition of insulin-induced glucose uptake. Interestingly, pretreatment of IFN-γ with IL-6 synergistically suppressed insulin signaling, even when IL-6 alone had no significant effect. These results indicate that type I and type II IFN induce insulin resistance by inducing distinct SOCS isoforms, and IL-6 synergistically augments IFN-γ-induced insulin resistance by potentiating STAT3-mediated SOCS3 induction in 3T3-L1 adipocytes.

Progesterone inhibits glucose uptake by affecting diverse steps of insulin signaling in 3T3-L1 adipocytes.

Maternal insulin resistance is essential for efficient provision of glucose to the fetus. Although elevation of placental hormones is known to relate to the development of insulin resistance, the precise underlying mechanism of maternal insulin resistance is unknown. Therefore, we examined the molecular mechanisms of progesterone causing insulin resistance in 3T3-L1 adipocytes. Progesterone at 10(-4) M, but not 10(-5) M, reduced the amount of IRS-1. As a result, insulin-induced phosphorylation of IRS-1, the association of IRS-1 with p85alpha, and subsequent phosphorylation of Akt1 and -2 was decreased moderately by 10(-4) M progesterone. Subsequently, insulin-induced translocation of GLUT4 to the plasma membrane evaluated by immunostaining on the plasma membrane sheet by confocal laser microscope was also decreased by 10(-4) M progesterone. In contrast, 2-[(3)H]deoxyglucose (2DG) uptake was markedly inhibited by both 10(-5) and 10(-4) M progesterone in a dose-dependent manner. Surprisingly, 2DG uptake elicited by adenovirus-mediated expression of constitutive-active mutant of PI 3-kinase (myr-p110) and Akt (myr-Akt) was suppressed by progesterone. Interestingly, insulin-induced tyrosine phosphorylation of Cbl and activation of TC10 were inhibited by progesterone at 10(-5) M. These results indicate that progesterone is implicated in insulin resistance during pregnancy by inhibiting the PI 3-kinase pathway at the step of 1) IRS-1 expression and 2) distal to Akt and 3) by suppressing the PI 3-kinase-independent pathway of TC10 activation by affecting Cbl phosphorylation.

A nontraumatic macular hole in a 10-year-old girl.

BACKGROUND: Full-thickness macular holes usually develop in the elderly population. To the best of our knowledge, there has been no written report of a nontraumatic macular hole in a pediatric patient. CASE: A 10-year-old girl noticed decreased central vision in her left eye without any history of trauma. OBSERVATIONS: Fundus examination of the left eye revealed a full-thickness macular hole and a thin fibrous membrane on the superior peripapillary retina. She underwent standard macular hole surgery with stripping of the membrane, resulting in closure of the hole. CONCLUSIONS: A full-thickness macular hole may develop in pediatric patients. Although the etiology of the macular hole in the present patient is unclear, tangential traction induced by contraction of the peripapillary membrane, presumed to be an incomplete regression of the Bergmeister papilla, might have been responsible for the formation of the macular hole.

Pars plana vitrectomy with gas tamponade for lamellar macular holes.

PURPOSE: To report anatomic and visual improvement after pars plana vitrectomy with gas tamponade for a lamellar macular hole with poor central visual acuity. DESIGN: Two interventional case reports. METHODS: Two patients with a lamellar macular hole underwent vitrectomy, internal limiting membrane peeling, and long-acting gas injection. Main outcome measures included best-corrected visual acuity, biomicroscopic appearance, and optical coherence tomography findings. RESULTS: Vitrectomy with gas tamponade resulted in biomicroscopic, functional, and tomographic improvement in both patients for follow-up periods of 12 months. CONCLUSIONS: Vitrectomy with gas tamponade may be an effective method for a lamellar macular hole with poor visual acuity.