[Efficacy of protein-free calf blood extract ophthalmic gel for diffuse punctate corneal epithelial defects].

OBJECTIVE: To evaluate the clinical efficacy of protein-free calf blood extract ophthalmic gel for diffuse punctate corneal epithelial defects. METHODS: 36 patients (36 eyes) with diffuse punctate corneal epithelial defects were enrolled between Oct. 2008 and Apr. 2009 in outpatient clinic from Eye Ear Nose and Throat Hospital of Fudan University. Patients were randomized divided into protein-free calf blood extract ophthalmic gel group (the test group, 19 eyes) and recombinant bovine basic fibroblast growth factor ophthalmic gel group (the control group, 17 eyes). The drugs were delivered in both groups 4 times per day, one drop each time in the 14 days duration. Corneal staining, the tear break-up time, the Schirmer value and visual acuity were evaluated on the pre-delivery day and the post-delivery day 14. RESULTS: On day 14, both the test group and control group had a significant decrease from baseline in corneal staining (the test group t = 5.7083, P = 0.0000 and the control group t = 4.5019, P = 0.0004, respectively). And improvements of corneal staining in the test group was more significant than that in the control group (t = 2.2712, P = 0.0296). Improvements were seen in BUT values in both group on day 14, as compared to baseline (the test group Z = 2.226, P = 0.0260 and the control group Z = 2.527, P = 0.0115, respectively). However, there was no significant difference between groups (Z = 1.336, P = 0.1815). As to the Schirmer value, there were neither difference within groups from baseline (the test group t = 0.4207, P = 0.6790 and the control group t = 1.1255, P = 0.2770, respectively). Nor between groups (t = 0.9830, P = 0.3325). And no obvious changes from baseline in visual acuity were observed in both groups (the test group Z = 1.897, P = 0.0578 and the control group Z = 1.786, P = 0.0741, respectively). CONCLUSION: The efficacy of protein-free calf blood extract ophthalmic gel is prior to recombinant bovine basic fibroblast growth factor ophthalmic gel in patients with diffuse punctate corneal epithelial defects.

[Comparative research of the efficacy of the gatifloxacin and levofloxacin for bacterial conjunctivitis in human eyes].

OBJECTIVE: To evaluate the different efficacy and safety to the treatment of bacterial conjunctivitis between the fluoroquinolone antibiotics gatifloxacin and levofloxacin. METHODS: A multi-centre, random, double-blind and control trial was performed in six centers including Eye Ear Nose and Throat Hospital of Fudan University, Henan Eye Institute, Eye Hospital Affiliated to Wenzhou Medical College, the First Affiliated Hospital Of Nanjing Medical University, Xijing Hospital Affiliated to the Fourth Military Medical University, the Second Affiliated Hospital of Xi'an Jiaotong University between August 2006 and October 2007. The levofloxacin was set as the efficient control. Two hundred and thirty-five patients (235 eyes) that diagnosed as bacterial conjunctivitis were randomly divided into two groups by the method of randomized blocks, the test group (gatifloxacin) had 118 eyes and the control (levofloxacin) group had 117 eyes. The drug delivery into conjunctival sac was performed at a 7-day period (two drops per time, eight times per day at the first two days and two drops per time, four times per day at the following 5 days). All participants were given the conjunctival sac germ culture and drug sensitive test before and after the study. The combination score of signs and symptoms and evaluation of safety were conducted at the pre-delivery day, the (4 ± 1) and (7 ± 1) delivery day. The statistic analysis was conducted by CMH χ(2) test, Pearson χ(2) test and Fisher's exact probabilities test. RESULTS: The efficacy of the two groups was 94.0% (110/117 eyes) in gatifloxacin group and 93.8% (106/113 eyes) in levofloxacin group with no significant difference (χ(2) = 0.052, P = 0.8201). There was also no difference in the bacteria clearance between the two groups [gatifloxacin versus levofloxacin, 94.1% (80/85 eyes) versus 92.5% (74/80 eyes), P = 0.3470]. The decrease of combination score of signs and symptoms at the (4 ± 1) delivery day was 4.436 ± 2.310 in the gatifloxacin group and 3.814 ± 1.962 in the levofloxacin group, the difference of which was significant (F = 7.280, P = 0.0075). This trend was also proved at the (7 ± 1) delivery day (gatifloxacin versus levofloxacin, 7.487 ± 2.821 versus 6.912 ± 2.911, F = 4.060, P = 0.0452). The visual acuity and the tolerance after local application of the eye drops between the two groups had no difference (the visual acuity F = 1.04, P = 0.3080; the tolerance after local admission χ(2) = 0.1372, P = 0.7111). According to the result of the germ culture, the major pathogenic bacteria were Gram-positive bacteria (totally 20 kinds of Gram-positive bacteria and 8 kinds of Gram-negative bacteria). The MIC and drug resistance of gatifloxacin to the Gram-positive bacteria was lower than that of the levofloxacin (Staphylococcus Epidermidis, Staphylococcus Aureus, coagulase negative Staphylococcus, α-hemolytic Streptococcus). CONCLUSIONS: The gatifloxacin eye drop has a good therapeutic effect to the bacterial conjunctivitis. It can effectively clear the pathogen with fast and strong effect. Moreover, it has a low MIC in vitro, advance a prospect in drug resistance, safety and ocular tolerance.

[Research on effects of vitamin A palmitate on repair of mechanical corneal epithelial defects and conjunctival goblet cells in rabbits].

OBJECTIVE: Randomized controlled experimental study to investigate the influence of vitamin A palmitate and bovine recombinant basic fibroblast growth factor (bFGF) on repair of mechanical corneal epithelial defects, conjunctival epithelial cells and goblet cells in rabbits. METHODS: One hundred and twenty New Zealand rabbits (all males) were selected to establish the mechanical corneal epithelial defects models (scratching out a round area with the diameter of 8 mm in the centre of cornea). Forty eight New Zealand rabbits were randomly divided into 4 groups: group A used lincomycin hydrochloride eye drops (LED) after the model had been established; group B used vitamin A palmitate eye gel and LED; group C used recombinant bFGF eye gel and LED; group D used vitamin A palmitate eye gel, bFGF eye gel and LED. Photo slit lamp examination and measurement of repaired area were performed on day 0, day 1, day 4 and day 7; transmission electron microscopy, histological microscope examination and impression cytology were performed on day 0, day 1, day 4 and day 7 to analysis the morphology and repairment of corneal epithelium, conjunctival epithelial cells and the goblet cells. The variants were tested using analysis of variance and Tukey's test. RESULTS: Statistic analysis showed that on day 1, the size of areas of repaired corneal epithelium was: group A(53.512 +/- 18.850) mm(2), group B (92.194 +/- 14.367) mm(2), group C (89.779 +/- 20.535) mm(2), group D (127.816 +/- 16.379) mm(2). The difference in size of repaired areas between different groups was statistically significant (F = 17.663, P = 0.000), with exception of the difference between groups B and C (P = 0.995). Conjunctival impression cytology showed that, the average number of conjunctival goblet cells per 740 microm x 550 microm at day 1 was decreased, group A (10.083 +/- 4.441), group B (10.667 +/- 3.551), group C (9.583 +/- 4.502), group D (9.167 +/- 5.606). The difference between these four groups was not significant (F = 0.239, P = 0.868). At day 4, the size of areas of repaired corneal epithelium was: group A (120.369 +/- 11.839) mm(2), group B (156.606 +/- 8.087) mm(2), group C (154.216 +/- 9.990) mm(2), group D (175.181 +/- 5.168) mm(2), which showed a significant difference between each two groups (F = 37.665, P = 0.000), with exception between groups B and C (P = 0.968). The average number of goblet cells at day 4 was recovered, which was: group A (41.250 +/- 4.575), group B (56.083 +/- 6.374), group C (48.417 +/- 4.562), group D (61.917 +/- 5.017), with a significant difference between these four groups (F = 36.210, P = 0.000). At day 7, the size of areas of repaired corneal epithelium had a statistical significance (F = 32.656, P = 0.000) between these four groups, which was group A (177.472 +/- 3.585) mm(2), group B (186.715 +/- 3.022) mm(2), group C (182.293 +/- 3.158) mm(2), group D (194.106 +/- 2.176) mm(2). The area of repaired corneal epithelium in group D was larger than that of other groups (P < 0.05). The average number of goblet cells was recovered significantly, which was: group A (63.167 +/- 11.488), group B (99.501 +/- 15.877), group C (82.015 +/- 9.175), group D (104.750 +/- 9.659). There was a significant difference in goblet cell number between these groups (F = 30.312, P = 0.000) with exception between groups B and D (P = 0.700). In transmission electron microscope examination of the cornea, we found that vitamin A palmitate and bFGF could both promote the development of intracellular conjunction. Vitamin A palmitate protected corneal epithelial cells, prevented cell keratinization, promoted proliferation and differentiation of corneal epithelial cells. In transmission electron microscopy examination of the conjunctiva, conjunctival goblet cells in groups B and D recovered well with rich secretary granules, which were quite different from groups A and C. Conjunctival epithelium of groups B, C and D were well-differentiated with tight intracellular conjunction. CONCLUSIONS: Vitamin A palmitate and bFGF could promote the repair of mechanical corneal epithelial defects and the development of intracellular conjunction. The effect is more significant when vitamin A palmitate is combined with bFGF. Vitamin A palmitate promotes regeneration of conjunctival goblet cells and can re-establish intracellular conjunction of conjunctival epithelium. The protective effect of vitamin A palmitate on conjunctival goblet cells is better than that of bFGF.

[Efficacy of protein-free calf blood extract for mechanical corneal epithelial defects in human eyes].

OBJECTIVE: To evaluate the clinical efficacy between protein-free calf blood extract eye drops and recombinant human epidermal growth factor (rhEGF) eye drops for mechanical corneal epithelial defects in human eyes. METHODS: A multi-center, randomized and double-blind study with a parallel, positive-control designation was carried out from April to November in 2005 at Department of Ophthalmology, Eye Ear Nose and Throat Hospital of Fudan University, Xinhua Hospital of Shanghai Jiaotong University, the First Hospital of Zhejiang University, the Second Hospital of Zhejiang University and Qingdao Municipal Hospital. 240 patients (240 eyes) with confirmed diagnosis of corneal epithelial defects at that six hospitals were enrolled in this study and were randomly arranged into two groups in average. One group (120 eyes) were treated by 20% protein-free calf blood extract eye drops which was defined as the experimental group while the other (120 eyes) by 5000 IU/ml recombinant human epidermal growth factor (rhEGF) eye drops as the positive control group. The drug was delivered in both groups 4 times per day, one drop each time in the 14 days duration. The symptoms and signs were scored and the safety was evaluated on the pre-delivery day, the third post-delivery day (day 3), day 7 and day 14. The variants in the study were tested for the different efficacy and safety between the two drugs using non-inferiority test, paired t-test, Wilcoxon signed-rank test, chi-square test, continuity correction chi-square test, Fisher's exact probabilities, analysis of variance, Cochran-Mantel-Haenszel chi-square test and so on. The criterion for statistical significance was P < 0.05. RESULTS: There was no significant difference in efficacy between the protein-free calf blood extract group and the recombinant human epidermal growth factor group (day 3: X2 = 1.5677, P = 0.4566, day 7: X2 = 1.7152, P = 0.4242, day 14: X2 = 3.0814, P = 0.2142). The total scores of symptoms and signs in experimental group had a obvious descending (6.009 +/- 3.030) compared with the positive control group with a descending of (5.177 +/- 2.582), which reached the significant level (t = 2.2367, P = 0.0263). Ocular local stimulates and general side effect were not observed within the treatment course. There was no significant difference between the two groups in the comparison of pre- and post-therapy visual acuity. The difference was not significant when comparing the uncomfortable feelings, including eye burning and eye itching (eye burning: day 3: X2 = 0.4394, P = 0.932, day 7: X2 = 1.4710, P = 0.479,day 14: X2 = 2.1875, P= 0.335, and eye itching: day 3: X2 = 2.1045, P = 0.349, day 7: X2 = 2.0192, P = 0.364, day 14: X2= 0.6863, P = 0.407). And the positive control group gave priority to the experimental group in comfortability. A better comfortableness was reported in the protein-free calf blood extract group on the third day post-delivery (X2 = 6.626, P = 0.0100). However, no obvious difference was examined on day 7 and day 14 post-delivery. CONCLUSION: Protein-free calf blood extract eye drops has confirmed efficacy, good safety, quick effect and better comfortableness.