Retinal Nerve and Vascular Changes in Prediabetes.

OBJECTIVE: This study aimed to observe vascular and neuroretinal alterations in people with prediabetes [impaired fasting glucose (IFG) and impaired glucose tolerance (IGT)] and normal glucose metabolism. METHODS: A total of 21 patients with prediabetes (42 eyes) and 20 healthy controls (40 eyes) participated in our study. All patients underwent a complete eye examination [including fundus fluorescein angiography (FFA) and optical coherence tomography (OCT)] and a related general examination (complete biochemical analysis, routine blood tests, and glycosylated hemoglobin). RESULTS: On FFA, no patients in either group showed any microvascular alterations. The total peripapillary retinal nerve fiber layer (pRNFL) in the prediabetic group was significantly thinner than that in the healthy control group (p < 0.0001). Only the temporal pRNFL thickness was significantly less in patients with prediabetes compared to the normal people. There was no significant difference in the thickness of retina in the range of 1 mm diameter of macular fovea (p = 0.286), but in the prediabetic group, the macular retinal thickness within the diameter of 6 mm in nasal side (p < 0.0001), superior side (p < 0.0001), temporal side (p = 0.008), and inferior side (p = 0.001) were lower than that in the control group. CONCLUSION: In the prediabetic group, there was no microvascular alterations, but the total pRNFL and the temporal pRNFL was significantly thinner, and the macular retinal thickness within the diameter of 6 mm in the nasal, temporal, and inferior side were lower than that in the healthy control group. These data confirm neuroretinal alterations in prediabetes prior to microvascular injury.

The heterozygous EDNRB mutation in a Chinese family with Waardenburg syndrome type I.

The genovariation of endothelin receptor type B (EDNRB) was identified in a Chinese family with Waardenburg syndrome type I (WS1) in the present study. WS1 was diagnosed in a 19-year-old young man, his older sister and aunt according to WS consortium criteria. After extracting genomic DNA from the peripheral blood samples, the coding exons and intronic regions of EDNRB were sequenced. A missense heterozygous mutation was found in the coding region of exon 2 in the EDNRB gene on chormosome 13q22.3 of the proband. The same mutation was detected in the proband's afflicted paternal aunt and first older sister. Subsequent polyphen analysis and three-dimensional modeling confirmed that the c.469A>G heterozygous mutation in EDNRB was possibly pathogenic. This is the first report of EDNRB mutation as a potential disease-causing mutation in Chinese patients with WS1.

Comparative Study of Recessive Spherical Headed Silicone Intubation and Endonasal Dacryocystorhinostomy under Nasal Endoscopy for Nasolacrimal Duct Obstruction.

Between July 2014 and November 2015, we compared the curative effects and cost-effectiveness of two kinds of nasal endoscopic surgery for nasolacrimal duct obstruction (NLDO) in a single-centre, two-armed clinical trial with a 1-year follow-up. We included two groups: a recessive spherical headed silicone intubation (RSHSI) group and an endonasal dacryocystorhinostomy (En-DCR) group; both received nasal endoscopy. Patients were recruited from the Otorhinolaryngology and Ophthalmology departments. The main outcome measures were epiphora improvement (classified as cure, effective, or invalid), cost-effectiveness, visual analogue scale (VAS) intraoperative pain score, bleeding volume, operating time, hospitalisation time, total cost, and VAS postoperative epiphora score. No significant group difference was identified in postoperative epiphora VAS scores (P > 0.050) or success rate (P = 0.406). However, average VAS intraoperative pain score, operating time, bleeding volume, hospitalisation time and total cost in the RSHSI group were clearly lower to those in the En-DCR group (P = 0.000). In conclusion, RSHSI under nasal endoscopy can provide similar treatment outcomes to En-DCR. RSHSI has advantages including minimal invasiveness, reduced risk, shorter duration of surgery and hospitalisation, reduced intraoperative discomfort, and lower financial burden, which is more acceptable to patients. Thus, RSHSI may be the preferred option for NLDO.

Relationship between serum bilirubin levels and optic neuritis.

BACKGROUND: Bilirubin is the end product of heme catabolism and has strong antioxidant properties. Serum bilirubin levels are reported to be reduced in patients with multiple sclerosis (MS) and neuromyelitis optica (NMO). The pathophysiology of optic neuritis (ON) resembles that of MS; however, the role of endogenous bilirubin in ON is unclear. The aim of this study is to measure serum bilirubin levels in patients with ON, and to investigate the correlation between ON and serum antioxidant status of bilirubin. METHODS: Serum levels of bilirubin were measured in 42 patients with ON, 50 patients with multiple sclerosis (MS), 48 patients with neuromyelitis optica (NMO) and 48 healthy control subjects. RESULTS: Serum total bilirubin (Tbil), direct bilirubin (Dbil) and indirect bilirubin (Ibil) levels in patients with ON were significantly lower than those in the healthy controls. However, no statistical significance was found between levels in the ON and MS, ON and NMO, and MS and NMO groups. In patients with ON, serum Tbil, Dbil, and Ibil levels were lower in those with recurrence or those with ON for a longer duration (≥ 1 year). Moreover, Tbil, Dbil, and Ibil concentrations were lower in patients with papillitis than in those with retrobulbar type ON, but the differences were not statistically significant. CONCLUSIONS: Low antioxidant status may exist in patients with ON. But serum levels of Tbil, Dbil, and Ibil did not correlate with clinical presentations, such as recurrence, duration of disease and subtypes of ON. Low antioxidant status already existed in MS or NMO patients before systemic symptoms appeared.

Relations between lymphangiogenesis and the size of pterygium.

AIM: To examine the relations between lymphangiogenesis and the size of pterygium. METHODS: Tissues from 88 primary and 34 recurrent pterygia were evaluated, and those from 7 nasal epibulbar conjunctiva segments were used as controls. Pterygium slices from each patient were stained with LYVE-1 monoclonal antibodies to identify lymphatic microvessel for calculating lymph-vascular area (LVA), lymph-microvascular density (LMD) and lymph-vascular luminal diameter (LVL). Also, the relations between lymphangiogenesis (measuring by LVA, LMD and LVL) and the size of pterygium (extension, width and area) were explored. RESULTS: There were a few LYVE-1((+)) lymphatic vessels in normal epibulbar conjunctiva segments. However, the number of lymphatic vessels slightly increased in primary pterygia and dramatically increased in recurrent pterygia. LVA, LMD and LVL significantly increased in recurrent pterygia in comparison with primary pterygia (all P<0.05). Both LMD and LVA were correlated with the width and area of pterygia (both P< 0.05), and LVA was also correlated with the extension of pterygia(P<0.05). CONCLUSION: Lymphangiogenesis is correlated with the size of pterygium. The outgrowth of lymphatic vessels might contribute to the development of pterygia.

[Dynamic aspects of corneal lymphatic vessels after keratoplasty in rats].

OBJECTIVE: To study the development of lymphatic vessels after keratoplasty and to explore the molecular mechanisms of corneal lymphangiogenesis in transplanted corneas. METHODS: Experimental research. The development of corneal lymphangiogenesis was examined by LYVE-1 immunohistochemistry and whole mount immunofluorescence 1, 3, 7, 10, 14, 30 and 60 days after corneal transplantation, then lymphatic vessels counting (LVC)was evaluated. The expression of vascular endothelial growth factor-C (VEGF-C) in transplanted corneas was examined by immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), and real time-PCR at same time. In addition, the inflammatory index (IF) was recorded at each time point. The association of VEGF-C and IF with LVC in transplanted corneas was examined. Analysis of the significance of differences between two groups was performed using paired Student's t-test. Pearson's analysis was used to analyze the correlation between VEGF-C, IF and LVC. RESULTS: Corneal lymphangiogenesis occurred in the stroma with LVC (1.8 ± 0.3) on Day 3, then developed and reached the peak with LVC (9.1 ± 1.5) on Day 14 after corneal transplantation. Both VEGF-C protein and mRNA up-regulated dramatically in rat transplanted corneas. The immunoreactivity reached the peak on the 3(rd) day and the 14(th) day after keratoplasty. Compared with the expression of VEGF-C mRNA (1.62 ± 0.08 copies/g) on Day 3, the expression of VEGF-C mRNA (2.48 ± 0.03 copies/g) significantly increased 14 days after the transplantation (t = 4.296, P = 0.02). LVC was strongly and positively correlated with IF (r = 0.55, P = 0.003) and the expression of VEGF-C mRNA (r = 0.51, P = 0.003). CONCLUSIONS: Corneal lymphangiogenesis correlates closely with corneal inflammation. The increased expression of VEGF-C in the cornea may be one of the important molecular mechanisms in the occurrence of corneal lymphangiogenesis after keratoplasty.

Relationship between angiogenesis and lymphangiogenesis in recurrent pterygium.

AIM: To examine the relationship between angiogenesis and lymphangigenesis in recurrent pterygia. METHODS: Tissues from 34 excised recurrent pterygia (including 12 Grade 1, 10 Grade 2, and 12 Grade 3) were involved in the study and tissues from 7 nasal epibulbar conjunctivae segments were used as controls. Sections from each pterygium were immunostained with CD(31) and LYVE-1 monoclonal antibodies to evaluate lymphatic microvessel density (LMVD) and blood microvessel density (BMVD), and the relationship between LMVD and BMVD in the pterygium was examined. RESULTS: There was a large number of CD(31) ((+))LYVE-1((-)) blood vessels but only a few CD(31) ((+))LYVE-1((+)) lymphatic vessels in grades 1 and 2 pterygium. However, lymphatic vessels were dramatically increased in grade 3 pterygium. LMVD correlated closely with BMVD in all pterygia, including grades 1, 2 and 3 peterygium patients (all P values <0.01). Although both the density of blood and lymphatic vessels increased in recurrent pterygia, lymphatic vessels developed much faster than blood vessels, especially in grade 3 pterygia. CONCLUSION: There is a significant but not parallel relationship between angiogenesis and lymphangiogenesis in recurrent pterygium. The outgrowth of blood and lymphatic vessels provide evidence that immunological mechanism may play a role in the development and recurrence of pterygium.

[The relationship between corneal lymphangiogenesis and inflammation index after corneal alkali injury].

OBJECTIVE: To discuss the relationship between corneal lymphangiogenesis and inflammation index (IF) in alkali burned corneas. METHODS: Experimental research. Rat corneal hemangiogenesis and lymphangiogenesis were examined by 5'-nase-alkaline phosphatase (5'-NA-ALP) double enzyme-histochemistry and whole mount immunofluorescence at 1 day, 3 days, and 1, 2, 3, 4, 5, 6, 7, 8 weeks after alkaline burns, and the blood vessel counting (BVC) and the lymphatic vessel counting (LVC) were recorded. The state of corneal inflammation was observed under the slit lamp and evaluated by inflammation index (IF) grading at the same time. Then, the association of LVC with IF was examined. In addition, eleven human alkali burned corneas were obtained from 11 patients undergoing corneal transplantation in Zhongshan Ophthalmic Center from January 2005 to June 2008. Corneal lymphangiogenesis was examined by lymphatic vessel endothelial receptor (LYVE-1) immunohistochemistry. The significance of the differences in IF, inflammatory cells counting, burn history, and age between two groups was analyzed by using paired student's t-test. RESULTS: New lymphatic vessels were present in rat alkali burned corneas. Corneal lymphangiogenesis developed 3 days after alkaline burns, reached the top 2 weeks after the injury, then decreased gradually, and disappeared at the end of the 5th week. Corneal lymphatics occurred behind corneal inflammation, but disappeared before corneal inflammation and hemangiogenesis. LVC was strongly and positively correlated with IF (r = 0.572, P < 0.01) after corneal alkaline burns. Among eleven human alkali burned corneas, corneal lymphatic vessels were present in 3 corneas. Compared with the other 8 cases without corneal lymphangiogenesis, the scores of IF was significantly higher (t = 3.28, P < 0.05), the inflammatory cells counting dramatically increased (t = 2.42, P < 0.05), but the age decreased significantly (t = 2.62, P < 0.05). However, the difference in burn history between two groups was not significant (t = 1.28, P > 0.05). CONCLUSION: Corneal lymphangiogenesis develops after alkaline-burns and correlates closely with inflammation index.

Corneal lymphangiogenesis correlates closely with hemangiogenesis after keratoplasty.

AIM: To examine the relationship between corneal lymphangiogenesis and hemangiogenesis after keratoplasty. METHODS: Nineteen human corneas were obtained from 19 patients undergoing a second corneal transplantation in Zhongshan Ophthalmic Center in 2005. Blood and lymphatic vessels in human transplanted corneas were identified by lymphatic vessel endothelial receptor (LYVE-1) and platelet endothelial cell adhesion modecule-1 (PECAM-1) immunohistochemistry, and double enzyme-histochemistry; then the association of corneal blood vessel counting (BVC) with lymphatic vessel counting (LVC) was examined. RESULTS: Corneal hemangiogenesis was present in 12 cases (63%), and lymphangiogenesis occurred in 5 cases (26%) human transplanted corneas. In addition, corneal lymphangiogenesis was only present in vascularized corneas. LVC was strongly and positively correlated with BVC (r=0.725, P<0.01). CONCLUSION: Corneal lymphangiogenesis develops after keratoplasty and strongly associates with hemangiogenesis.

[Effects of mutant kringle 5 eye drops on the survival time of corneal allografts in rat].

OBJECTIVE: To investigate the preventative effect of mutant kringle 5 (mK5) eye drops on corneal allograft rejection. METHODS: It was a experimental study. The outbred strain F344 and Lewis rats were used as donors and recipients respectively. Sixty Lewis rats were randomly divided into B, C, D and E Group; Group A, F344 rats autograft control; Group B, allograft control (the control groups were given normal sodium only); Group C and D, allograft groups, were treated with 5 mg/L and 10 mg/L mK5 eye drops respectively; Group E, allograft group, was treated with 0.1% dexamethasone eye drops. The eye drops were applied one drop four times per day for two weeks, the occurrence and development of corneal allograft rejection and corneal neovascularization (CNV) was observed every other day by slit-lamp microscope, the grafts were evaluated clinically by means of Holland's scoring system and the area of CNV was calculated. Nine rats per group were killed on the 14th day, and the corneas were taken for histopathological examinations. Analysis of variance was used to analyze the outcomes. RESULTS: The average graft survival time of Group B, C, D and E was (9.3 +/- 2.1), (21.1 +/- 7.3), (23.5 +/- 10.8) and (28.2 +/- 19.1) d respectively, Compared with Group B, Group C and D had a statistically significant prolongation of survival time (q = 10.24, 13.47; P < 0.05). Though treated with 0.1% dexamethasone eye drops (Group E) prolonged transplant survival time as compared with mK5 eye drops, but the difference was not statistically significant (q = 2.54, 1.49; P > 0.05). The occurrence of CNV in Group A was (3.1 +/- 0.8) d, Group B (2.6 +/- 0.5) d, Group C (6.4 +/- 0.5) d, Group D (7.8 +/- 0.7) d and Group E (5.3 +/- 1.0) d. Significant difference (q = 31.58, 51.21, 19.98; P < 0.05) was found between groups C, D, E and Group A. There were also significant difference between groups C, D, E and Group B (q = 43.87, 67.14, 24.53; P < 0.05). The CNV areas of Group C and Group D were also smaller than Group B (q = 30.76, 62.14; P < 0.05). The results was similar compared with Group E (q = 15.20, 25.64; P < 0.05). Fewer inflammatory cells and CNV were found in the cornea of the groups treated with mK5 eye drops. CONCLUSION: Topical application of mK5 eye drops can prevent corneal graft rejection and corneal neovascularization in rats.

[Exploration of lymphangiogenesis in alkali burned human cornea].

OBJECTIVE: To explore the lymphangiogenesis process in alkali burned human cornea and to discuss factors modulating this process. METHODS: It was a retrospective case series study. Twenty-two cases (22 eyes) of hospitalized patients suffering from alkali burned cornea and requiring keratoplasty from January to December 2005 were analyzed retrospectively. Before surgery, injury time (IT) and injury degree (ID) were recorded. Furthermore, inflammation index (II) and relative area of new blood vessels (BVA) were measured. Cornea specimens were assessed for lymphatic vessel counting (LVC) and blood vessel counting (BVC) via immunohistochemical staining and transmission electronic microscopy. Meanwhile, HE staining was also performed to observe infiltration of polymorphonuclear (PMN) leucocytes in corneal tissues. Student t-test, Pearson correlation test and Stepwise regression analysis were used to investigate the influencing factors. RESULTS: In these 22 cases, IT was (57.62 +/- 31.72) months; ID was (12.00 +/- 2.76) scores; II was (2.32 +/- 2.63) scores; BVA was (29.79% +/- 18.61%); BVC was (14.45 +/- 9.29) units; LVC was (2.73 +/- 4.57) units and PMN was (13.45 +/- 13.09) units. In 7 patients with IT more than 64 months (accounted for 32% of 22 cases), lymphangiogenesis [(8.6 +/- 3.8) units] and hemangiogenesis [(22.3 +/- 11.1) units] were both present. In these 7 patients, the whole number of LVC was 60 units, constituting 16% of all vessels (BVC+LVC = 378 units). The correlation coefficient of LVC with IT, ID, BVA, PMN and II was -0.673, 0.604, 0.755, 0.806 and 0.873, respectively. P value of all these correlations was less than 0.05. Further regression analysis revealed that LVC could be approximately calculated from II and BVA multiplying certain constant coefficients separately (resulting in lymphatic index, LI). Lymphatic vessels with characteristic ultrastructures and inflammatory cells were identified by transmission electronic microscopy. CONCLUSIONS: Lymphatic vessels exist in part of alkali burned human corneas and may be estimated through II and BVA indirectly. Lymphatic index may be a convenient and useful clinical index for evaluating lymphangiogenesis in corneal alkali burn.