Associations of Diabetic Retinopathy Severity With High Ambulatory Blood Pressure and Suppressed Serum Renin Levels.

CONTEXT: The relationships between serum renin levels, severity of diabetic retinopathy (DR), and 24-hour blood pressure (BP) have not been previously reported. OBJECTIVE: To explore causes for DR and the relationships of 24-hour ambulatory BP, and hormone levels with the severity of DR. METHODS: The diabetic patients were classified as having no DR, simple DR, or severe DR (preproliferative DR plus proliferative DR) based on funduscopic examination, and we measured 24-hour BP, serum active renin (ARC), aldosterone (SAC), adrenocorticotropic hormone, and cortisol levels in each group. RESULTS: Compared to those with no DR or simple DR, patients with severe DR showed significantly higher 24-hour BPs, including daytime and nighttime systolic and diastolic BP levels, independent of diabetic duration and HbA1c levels. The variability of nighttime systolic BP was greater in patients with severe DR than in those with nonsevere DR, although nocturnal BP reduction was similar between the groups. The ambulatory BPs were significantly inversely associated with ARC. The ARC was significantly lower in severe DR patients than in those with no DR or simple DR (3.2 [1.5-13.6] vs 9.8 [4.6-18.0] pg/mL, P < .05), but there were no differences in SAC in patients taking calcium channel blockers and/or α-blockers. No associations were found between DR severity and other hormone levels. CONCLUSION: Severe DR was associated with higher 24-hour BPs and suppressed ARC. These findings suggest that mineralocorticoid receptor overactivation may play a role in higher BP levels and severe DR in diabetic patients.

Severe foveal hypoplasia and macular degeneration in Stickler syndrome caused by missense mutation in COL2A1 gene.

BACKGROUND: The aim is to determine the retinal changes in patients with Stickler syndrome caused by a p.R565C missense mutation of the COL2A1 gene. METHODS: We reviewed the clinical records of 10 eyes of six patients from two families with the Stickler syndrome. The members of both families were heterozygous for the p.R565C mutation. The clinical features including the visual acuity, fundus appearances, fundus autofluorescence (FAF), optical coherence tomographic (OCT) images, and electroretinograms were examined. RESULTS: Myopia of -12 diopters (D) to -24 D with an average of -16.8 D was observed in 9 eyes of the 5 patients. The FAF images showed different degrees of hyper and hypoautofluorescent patterns in the macula in all but the two youngest patients (7 of 9 eyes, 78%). The OCT images showed the absence of a foveal pit and destruction of the outer retinal layers in the macular area in all patients. The ellipsoid zone (EZ) in the macular region was disrupted in eight eyes (80%) of which seven were fovea sparing. CONCLUSION: Two families with Stickler syndrome with the p.R565C mutation showed more severe foveal hypoplasia, macular degeneration, and extensive retinal degeneration. A correlation of the OCT and FAF images with the genotype is helpful in determining the prognosis of Stickler syndrome.

Deep Anterior Lamellar Keratoplasty and Peripheral Lamellar Keratoplasty for a Case of Severe Peripheral Ulcerative Keratitis.

We experienced a rare case of severe peripheral ulcerative keratitis in a patient undergoing surgery combined with deep anterior lamellar keratoplasty (DALK) and peripheral lamellar keratoplasty (LK). A 63-year-old Japanese woman was referred to our hospital for the treatment of visual disturbance caused by peripheral ulcerative keratitis in the left eye. Although the inflammation subsided with topical and oral administration of steroids, peripheral ulcerative keratitis worsened 4 weeks after the medical treatment. Surgery combining DALK and peripheral LK, including the corneal limbus, was performed as treatment. Two weeks after the surgery, a double anterior chamber appeared, but it disappeared spontaneously. There was no postoperative rejection or intraocular pressure elevation. One year and 6 months after the surgery, the inflammation did not recur, the cornea remained transparent, and the thickness of the cornea was maintained. In conclusion, combined DALK and peripheral LK may be a surgical option for treating severe peripheral ulcerative keratitis.

[Philadelphia chromosome-positive acute lymphoblastic leukemia relapsing with an anterior chamber lesion of the eye].

A 48-year-old Filipino woman underwent umbilical cord blood stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia under non-remission status. Left aqueous humor puncture was performed owing to the development of left eye pain and exacerbation of anterior eye chamber inflammation 72 days after the transplantation; this revealed the relapse of leukemia in the anterior chamber. Subsequently, the patient tested positive for peripheral blood minimal residual disease. Therefore, doctors should take note that anterior chamber disease may appear as a non-typical relapse of leukemia.

Prognostic Factor Analysis of Intraocular Pressure with Neovascular Glaucoma.

Purpose. To perform multivariate analysis for identifying independent predictors of elevated intraocular pressure (IOP) with neovascular glaucoma (NVG), including antivascular endothelial growth factor (VEGF) intravitreal injections. Methods. We retrospectively reviewed 142 NVG patients (181 eyes) with ischemic retinal diseases [proliferative diabetic retinopathy (PDR) in 134 eyes, retinal vein occlusion (RVO) in 29, and ocular ischemic syndrome in 18]. We analyzed age, gender, initial/final LogMAR VA, initial/final IOP, extent of iris and/or angle neovascularization, treatments, preexisting complications, concurrent medications, and follow-up duration. Results. The mean follow-up duration was 23.8 ± 18.8 months. At the final follow-up, 125 (72.3%) eyes had IOP ≤ 21 mmHg. NVG patients with RVO had a higher degree of angle closure and higher IOP. NVG with PDR had better IOP and LogMAR VA. Angle closure had the greatest impact on final IOP. Greater than 90% of patients treated with trabeculectomy with mitomycin C (LEC) had persistent declines in IOP (≤21 mmHg). Stand-alone and combination anti-VEGF therapies were not associated with improved long-term prognosis of IOP. Conclusions. Angle closure was found to have the greatest effect on NVG-IOP prognosis. When target IOP values are not obtained after adequate PRP with or without anti-VEGF, early LEC may improve the prognosis of IOP.

The PI3K/Akt pathway mediates the expression of type I collagen induced by TGF-ß2 in human retinal pigment epithelial cells.

PURPOSE: Transforming growth factor (TGF)-ß is a key mediator of proliferative vitreoretinopathy, but the cellular mechanisms by which TGF-ß induces extracellular matrix protein (ECM) synthesis are not fully understood. This study examined whether the PI3K/Akt pathway is involved in TGF-ß2-induced collagen expression in human retinal pigment epithelial cells. METHODS: Human retinal pigment epithelial cells ARPE-19 were cultured and stimulated with TGF-ß2. The role of the PI3K/Akt pathway was evaluated using the biochemical inhibitor, wortmannin. The effect of wortmannin on the expression of type I collagen mRNA (COL1A1, COL1A2) induced by TGF-ß2 was evaluated by real-time RT-PCR. The effect of wortmannin on the synthesis of type I collagen induced by TGF-ß2 was assessed by an immunocytochemical analysis with anti-type I collagen antibody. Luciferase reporter assays were performed to examine the effect of wortmannin on the transcriptional activities of COL1A2. A luciferase assay using a mutation construct of the Smad binding site in COL1A2 promoter (Smad-mut/Luc) was also performed to examine the crosstalk between the Smad pathway and the PI3K/Akt pathway. The effects of wortmannin on the transcriptional activity of Smad3 were also examined using CAGA12-Luc. Moreover, the effect of wortmannin on TGF-ß2-induced Smad7 mRNA expression was evaluated. RESULTS: The biochemical blockade of PI3K/Akt activation inhibited TGF-ß2-induced type I collagen mRNA expression and type I collagen synthesis. The blockade of PI3K/Akt pathway inhibited the increase in COL1A2 promoter activities when induced by TGF-ß2 and reduced TGF-ß2 induction of Smad-mut/Luc promoter activity and CAGA12-Luc activity. Moreover, wortmannin increased the TGF-ß2-induced Smad7 mRNA expression levels. CONCLUSIONS: The PI3K/Akt pathway plays a role in relaying the TGF-ß2 signal to induce type I collagen synthesis in the retinal pigment epithelium through Smad-dependent and Smad-independent pathways.