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Group B
KPro in rabbit cornea In eight eyes PHEMAPMMA KPros was implanted. Two months after the stage I surgery, anterior lamellar cornea gradually dissolved in two of those and hence, further follow up was discontinued. KPro in one eye extruded one month after operation without cornea melting or perforation, so we continued to operate the second part on it.
Figure 6 TEM fibroblast in the sponge spore（12000×）（略）
Figure 7 Three months after stage I of KPro （略）
Figure 8 Two and half months after Stage II of KPros implantation in the rabbit eye, the central core is transparent（略）
Figure 9 Three months after Stage I of KPros implantation in monkey eye, the anterior cornea is slightly opacity（略）
There five eyes had no obvious complication and received the stage II surgery (Figure 7).
Six eyes received Stage II operation. During the observation, two eyes had little transparent crystal in central core, while the other four eyes were completely transparent. Following three to six months, we didnt find complications such as KPro extrusion, retroprosthetic membrane, anterior synechia, posterior synechia or cataract. Both central and peripheral anterior chamber were normal.However, in four eyes fibrous membrane in front of the KPro, occluding the pupil area was noted.
Figure 10 Three months after Stage II of KPros implantation in monkey eye, pupil can be seen without exudation（略）
Figure 11 Three months after Stage II of KPros implantation in monkey eye, anterior angle is open seen by UBM（略）
In the other 2 eyes central cornea was still transparent till end of the research work (Figure 8).
KPro in monkey cornea KPro implantation was done in two monkeys eyes. There were minor complications in either in stage I surgery or stage II surgery.
In pupil area, there were little exudation in anterior chamber after stage I surgery, and the exudation were absorbed within one week. During one to two weeks after surgery, there was lowgrade edema in corneal stroma, and there were hydrops between KPro and posterior lamellar cornea. We examined the eye pressure with finger. The eye pressure was normal or low. The pupil was round; neither anterior synechiae nor posterior synechiae were observed. One month later, there was angiogenesis in anterior lamellar.Two to three months later, ocular surface was stable, so we could prepare to do stage II surgery (Figure 9).
During stage II surgery, we didnt find adhesion between anterior lamellar and the KPro central core, and there was no leakage, exudation or posterior membrane. The depth of central chamber was normal. The pupil was round and there was no cataract. There was little transparent crystal in the central core of one eye . The other eye was transparent. Three months later, central transparent area remained clear. Neither anterior fibrous membrane nor posterior membrane was observed. Anterior chamber and lens were normal (Figure 10).
UBM and Bscan UBM: Anterior chamber angle was open in each quadrant, root of iris was flat and no anterior synechia in 1 eye. There was slight bulge in root of iris, anterior synechiae in 910 clock and narrow anterior chamber angle nearby in another eye (Figure 11).
B scan: There was no vitreous opacity or retinal detachment in both eyes.
DISCUSSION
The Research of Porous Skirt Early in 1789, De Quengsy suggested using KPro to replace turbid cornea, but the research about KPros developed slowly since that time. The main complication of prosthokeratoplasty was, and still is, the spontaneous rejection of prosthesis, known as "extrusion". The modern period began in the late 1940s, with the introduction of synthetic polymers as materials for KPros[5]. Scientists gradually recognized that corneal cells needed to grow into porous skirt of KPro in order to make the adequate healing and biocolonization between the skirt region of KPro and the host cornea. Therefore, researchers concentrated on the porous skirt of KPro. PHEMA was relatively superior to other high molecular materials[6,7]. In this study, we did animal experiments with PHEMA sponge. The histopathology results showed that cells had grown into PHEMA sponge two weeks after operation. Then angiogenesis began to occur along with cells growth. Because of operative wound and slight foreign body reaction the spongy material in lamellar pocket aroused inflammation in a short time.
But inflammation became less as would started healing. Immunohistochemistry results showed that the cells in porous sponge were homologous with corneal stroma cells. Both of them belonged to fibroblasts of cornea stroma. TEM examination showed that cells grew exuberantly in pores of spong. The rough endoplasmic reticulums and chondriosomes were active and there were much collagen and extracellular matrix. It means that PHEMA sponge had good histocompatibility to let cells grow into it. Furthermore, those cells could secrete collagen and extracellular matrix to combine with the corneal tissue authentically.
The Modified KPros PHEMA, a hydrophilic polymer, is a biomaterial with a convincing record of ocular tolerance in previous applications(contact lenses, intraocular lenses, intracorneal inlays).PHEMA gel is transparent, stretchy and has good air permeability. The characteristics of PHEMA are just like those of cornea. So it is an ideal material for KPros. The results of our research and other similar studies have proved that PHEMA sponge had good histocompatibility to heal within the corneal tissue[8,9]. Thus it was the best material to be porous sponge of KPro. But no matter the transparent gel or porous hydrophilic sponge, their tenacity was too bad to endure certain pressure. The Australian scientists have studied KPros for many years. They applied many different crosslinking agents to strengthen the mechanical resistance of material. We aimed to find a solution for this problem.
PMMA was a transparent carbonaceous macromolecule organic material. It had been made into intraocular lenses successfully for many years[10,11]. Comparing with PHEMA, PMMA had better tenacity and stretching resistance. But it was hard for PMMA to combine with corneal tissue.
After doing some experiments, we found that when we added some PMMA into PHEMA we would synthesize homogeneous PHEMAPMMA water gel without affecting the aggregation of PHEMA. The stretching resistance of this material was at least two times higher than simple PHEMA water gel. There was a thin layer of PHEMAPMMA gel on the bottom of modified KPro spongy skirt. Because of many laser holes in this layer provided good environment for suturing and tissue healing, thus allowing cells to grow into the interspace of porous sponge skirt so that complete biological healing between KPros and host corneas occurs . Theoretically, the stretching resistance of modified KPro was better than the Australian Chirila KPro. But it should be further verified by animal experiments if KPro could reduce the incidence of KPro extrusion after implantation.
Results of KPro Implantation and Other Unsolved Problems The extrusion of KPro after implantation was the biggest problem for a long time in this field. In this study, we improved the components and patch design of KPro . The modified KPro seldom emerged in our observational duration. That probably related to the improvement of patch design. In addition, the results of long time observation after implantation were still dependent on followup survey.
The chief complication of KPro implantation was the formation of anterior proliferative fiber membrane. The incidence increased with time. The membrane completely covered visual area in some cases. The possible reasons for this could be: 1) Patch design was needed to modify further. The chief reason of anterior membrane formation was that central lens was umbilicate. So fibroblasts grew to the front of lens and covered visual area. At present, we are improving this kind of patch and increasing the height of central lens in order to decrease the incidence of anterior membrane formation. 2) Inflammation on ocular surface was involved in anterior membrane formation. Reinforcing the using of local antiinflammatory agent could improve it. 3) The improvement surgical technique i.e simple central anterior lamellar resection be replaced with lamellar resection combined oral mucous membrane transplantation, the incidence of anterior membrane formation would be decreased.
There was anterior lamellar melting in 25% cases after stage I operation. That maybe correlated to the local ischemia and hypoxia early after KPro implantation. Theoretically, if we used bulbar conjunctiva to cover the KPro in the end of stage I operation, the incidence of cornea melting would be decreased. That is because bulbar conjunctiva could not only strengthen the KPro but also enhance the supply of nutrition.
CONCLUSION
The PHEMA sponge could obtain a tight fusion with the host cornea. KPros were stable 36 months after operations. We did not observe many serious complications.
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