Study Of Adverse Reactions About Oculentum Entering The Subconjunctival Tissue

PurposeOculentum is widely used in the treatment of eye disease, and the medicine density can be kept effectively in the conjunctiva sac for a long time. It is mainly manufactured by pharmaceutical ingredients and excipients, if the excipients are different, the adverse reactions caused by eye oculentum to the surface of ocular or the position affected by drugs are different. In recent years, researchs in many documents point out that the oculentum can sustain the lacrimal duct and avoid the lacrimal duct being conglutinated again if it is applied to lacrimal surgery, but the oculentum can also cause severe inflammation and it is hard to be treated if it goes into the subconjunctival tissue, orbital tissues, the tissue surrounding lacrimal sac and the eyelids through the false passage caused by surgery or trauma.The purpose of the experiment is to observe the adverse reactions caused by the different substrate oculentum when they are going into the subconjunctival tissue. The eye oculentums, which have little side effects and can be degraded and absorbed, are selected. This can provide experimental evidence and plays a role of instruction for the selection of eye oculentums in the clinical work.Materials and methods 1. Animals and Grouping72 guinea pigs, which are healthy and in clean level,2 to 4 weeks old, weighing 120～150 g, were selected. Male and female was open, and excluded a variety of eye diseases. They were randomly divided into three groups of A, B, C, and 24 in every group.2. Animal model productionAfter the ocular surface anesthesia by the eye drops of hydrochloric acid Ao Buka, the erythromycin eye oculentum, which takes vasline, lanolin and liquid paraffin as substrate, was injected into upper subconjunctival tissue of the right eye of guinea pigs in 0.2ml using 1 ml syringes and 7 (22 G) needle under the microscope in group A. The ofloxacin eye oculentum, which takes the sodium hyaluronate and carbomer as substrate, was injected into upper subconjunctival tissue of the right eye of guinea pigs in 0.2ml in group B. The hydroxypropyl methylcellulose was taken as a contrast and was injected into upper subconjunctival tissue of the right eye of guinea pigs in 0.2ml in group C.3. Project and time pointsTo observe the accumulative situations after the three drugs were injected into the subconjunctival tissue immediately;the swelling of the conjunctiva on the day of 1d,3d,7d,14 d,21 d,28 d were observed, just as 0,+,++,+++:0 shows it is have no obvious swelling,+shows the conjunctival edema is flat elevation and have no wrinkle,++shows the conjunctiva is upheaved and the area of palpebral fissure is visible,+++shows the conjunctiva is upheaved like the bubble and escaped from palpebral fissure, and the conjunctiva which is severe swelling covered the upper edge of the cornea partially; the diffusion, degradation and absorption of drugs at the above of six time were observed, the histopathological changes of the conjunctiva at the six time above were observed.4. Statistical analysisSPSS17.0 statistical software was used for statistical analysis. The method of Rank sum test was used to analyze the difference rates of the conjunctival swelling among the three groups. Inspection standard was 0.05, and P<0.05, so it had statistical significance. Results1. The situation of the three drugs injected into the local positionThe situations were observed immediately after injection, Group A of drugs looked like the thick oil which was yellow and white under the conjunctiva. Group B of drugs looked pale, white and translucent. Group C of drugs were liquid and transparent under the conjunctiva.2. The swelling degree of conjunctiva after the injection of three drugsGroup A:most swelling degree of the conjunctiva was +++, significant changes occurred on the 14th day,0 eye showed +++. On the 21th,28th day, the swelling of the conjunctiva was still seeing, and there was no significant regression. Group B: most swelling of conjunctiva was ++, the swelling degree of conjunctiva was significantly reduced on the 14th day, and the scope was significantly reduced too. On the 28th day, the swelling of conjunctiva was completely withered up. Group C: most swelling degree of conjunctiva was +, the swelling of the conjunctiva was gradually reduced in 7th day. On the 14th day, the swelling of the conjunctiva was completely subsided.1 d,3 d,7 d the difference rates of the conjunctival swelling among the three groups showed less than 0,05, there was significant difference between the three groups(P<0.05).3. The situation of drug diffuse and degradation and absorptionGroup A:after injection of eye oculentum, on the 3th day, eye oculentum was spreading to the bottom of the ball of the conjunctiva aroudly, but had no significant degradation and absorption. Group B:from the 3th day, eye oculentum was spreading to the blow of subconjunctival tissue, and was gradually degraded and absorbed with the diffusion, on the 28th day, the oculentum was completely absorbed. Group C:the drug was not diffused at each time and was degraded and absorbed at the first day after injection, and it was completely absorbed on 14th day.4. Histopathological changesGroup A:there were inflammatory cells, which were mainly consisted of neutrophil, could be seen in the conjunctival tissue, including lymphocytes, and a large number of fibrous tissue could be seen. The fibrous tissue proliferated and inflammatory cells disappeared on the 21th and 28th day. Group B:there were also inflammatory cells, which were mainly consisted of neutrophil, could be seen in the conjunctival tissue, peripheral vasodilation, had only a small amount of fibrous tissue; on 28th day, conjunctival structure returned to normal. Group C:there were only a small amount of inflammatory cells infiltrated into the conjunctiva tissue, inflammatory cells disappear on 7th day, and have no hyperplastic fibrous tissue, on 14th day, the structure of conjunctiva returned to normal.ConclusionWhen the erythromycin eye oculentum, which takes the vasline, lanolin and liquid paraffin as substrate, was injected into the conjunctival tissue, it would cause the worst inflammatory reaction, therefore, it was not recommended for the tissue of a wound surface.When the ofloxacin eye oculentum, which takes the sodium hyaluronate and carbomer as substrate, was injected into the conjunctival tissue, it would cause slight inflammatory reaction, and it could be used in the lacrimal surgery to play a part in supporting and preventing the tissue to adhesion.The hydroxypropyl methylcellulose did not cause significant inflammatory reaction, but it was not used to inject to the lacrimal because of its low viscosity.