Volume 39 ·  Issue 10 ·  2003

To evaluate the results of keratoprosthesis for complicated corneal opacities unsuitable for keratoplasty.

Fifteen keratoprosthesis were implanted in 15 patients with bilateral blindness. Preoperative visual acuity (VA) was light perception in all operated eyes. The corneal opacities were caused by severe alkali burn (6 eyes), sulfate acid injury (3 eyes), melting aluminum injury (2 eyes), explosive injury (1 eye), severe dry eye (1 eye) and multi-keratoplasty failure (2 eyes). The keratoprosthesis (MICOF®) were made by Moscow eye microsurgery complex in Russia. Surgical techniques consisted of two stages; first, inserting a supporting titanium frame into the lamellar pocket and then, implanting an optical part 3 months later.

Follow-up time ranged from 4 to 26 months (9.5 months on average). In 14 of 15 eyes (93%), postoperative VA ranged from 0.12 to 1.0 without correction. Corrected postoperative VA was: 7 eyes (47%) with VA from 0.6 to 1.2; 5 eyes (33%) from 0.3 to 0.5 and 2 eyes (13%) from 0.15 to 0.2. The reason of the only eye without VA improvement was a pre-existing retinal detachment.

Keratoprosthesis improves vision for corneal opacity patients with complicated conditions such as dense neovascularization and severe ocular surface disorders.

To study whether Chinese patients with various corneal dystrophy carry mutations in BIGH3 gene.

Genomic DNA was extracted from Chinese patients with Avellino corneal dystrophy (ACD, 10 cases), Reis-Bucklers corneal dystrophy (CDRB, 2 cases), granular corneal dystrophy (GCD, 3 cases) and 5 control subjects. The exons 4 and 12 of BIGH3 gene were amplified by PCR and the product was sequenced directly.

All 15 patients carried mutations in BIGH3 gene, R124H in 10 cases with ACD, R124L in 2 cases with CDRB and R555W in 3 cases with GCD.

Corneal lesions in all 15 Chinese patients clinically diagnosed with corneal dystrophies are caused by mutations in BIGH3 gene. Dose-effect analysis shows that corneal lesions are more severe in homozygous patients than those in heterozygous cases and that clinical manifestation of patients with R124L mutation is more severe than that of patients with R124H mutation.

By detecting the expression of IL-1RI and TGF-β₁ on the normal rat cornea and graft, and the amount of IL-1β in the aqueous humor of normal rat eye and the eye after keratoplasty, to investigate the relationship between these cytokines and graft rejection and to observe the effects of IL-1 receptor antagonist (IL-1ra) on graft rejection.

All rats after keratoplasty were divided into five groups. Immunohistochemistry method and enzyme-linked immunosorbent assay (ELISA) were used to detect the expression of IL-1R I and TGF-β₁ on the normal rat cornea and graft and the amount of IL-1β in the aqueous humor of normal rat eye and the eye after keratoplasty at different time points: pre-rejection, acute-rejection and two weeks after surgery.

IL-1R I could be detected in normal rat cornea. TGF-β₁ expressed mainly in the epithelium of normal cornea, especially the basal cell layer and the basement membrane. After keratoplasty, IL-1R I and TGF-β₁ could be detected in the corneal epithelium, stroma and endothelium, and the level of expression decreased in sequence as negative control group, 50 μg IL-1ra group, 100 μg IL-1ra group, 200 μg IL-1ra group and dexamethasone group. In the acute rejection period, the expression of IL-1R I and TGF-β₁ in the 200 μg IL-1ra group was less than that of the 50 μg IL-1ra group, the difference was significant (P< 0.01). The expression of IL-1R I and TGF-β₁ in the negative control group was higher than that of all experi mental groups, the difference was significant (P<0.01). IL-1β was detected in normal aqueous humor; the mean level was (96.0 ± 11.3) ng/L. In the eye after keratoplasty, the IL-1β level increased significantly compared to normal aqueous humor (P<0.01). In the acute rejection period, the quantity of IL-1β reached its peak at (552.2 ± 68.3) ng/L in the negative control group, which was the highest quantity of IL-1β in all experimental groups (P< 0.01). The IL-1β level in all experimental groups in the pre-rejection period had no difference compared with that in the acute rejection period (P> 0.05), but the level of IL-1β in the pre-rejection and rejection periods was significantly different compared with that in the post-rejection period (P<0.01).

IL-1R I and TGF-β₁ play a active role in the corneal graft immunogenic rejection. IL-1β is a key factor in starting corneal graft rejection. The keratoplasty graft rejecting reaction can be reduced and mean survival time can be prolonged by IL-1ra, which inhibits the expression of IL-1R I and TGF-β₁ and decreases the level of IL-1β in the aqueous humor.

To investigate the role of interleukin-10 (IL-10) in herpetic stromal keratitis (HSK).

Eighty BALB/c mice were divided into two groups and infected with HSV-1 Mckrae strain by corneal scarification. Murine rIL-10 (20 ng/ml) was inoculated intracorneally 6 h before and again on days 0, 2 and 4 after topical HSV-1 corneal infection. rIL-10 (500 ng) was given intraperitoneally in treated mice simultaneously. The same amount of saline was injected into the control mice. The effects of IL-10 on HSK were evaluated.

In the IL-10-treated animals, the onset of HSK was delayed, corneal stromal opacification and neovascularization were reduced, extensive cellular infiltrates in the cornea were prevented and delayed type hypersensitivity (DTH) was weakened. Examination of pro-inflammatory cytokine levels in the cornea 10 days after the infection revealed that the amounts of IL-2 and IL-6 were lower than those found in the controls. IL-10 did not suppress the viral replication nor did it eliminate the virus from IL-10-treated eyes, as compared with the controls.

IL-10 treatment can suppress DTH responsiveness and the production of certain cytokines by corneal cells. It delays the onset and decreases the severity of HSK.

To evaluate the result of surgery for senile cataract with Fuchs' endothelial dystrophy and emphasize the importance of the preoperative examination by specular microscopy.

In the review of 2 026 consecutive senile cataract cases, 17 Fuchs' endothelial dystrophy cases were found before cataract surgery by specular microscopy. Operative procedures and corneal endothelial protective measures were recorded, and postoperative corneal transparency was observed. The examination of specular microscopy was performed 3 months after the cataract surgery.

The incidence of Fuchs' endothelial dystrophy in senile cataract was 0.8% (17/2 026) in our study. The loss rate of endothelial cells was 16.2%. No bullous keratopathy occurred in all cases during follow-up period.

Reasonable measures to protect the endothelium in the surgery by an experienced operator is helpful to the success of surgery. Observing the endothelium by specular microscopy before cataract surgery is very important.

To evaluate the safety and efficiency of Dodick-ARC photolysis machine (a kind of Nd: YAG laser system) in the using of cataract surgery.

52 eyes of cataract (fifty-two patients) were undergone photolysis with Dodick-ARC laser system and foldable intraocular lenses (IOLs) implantation. The hardness of nuclei was graded as N_1.0 to N_4.0 of LOCS III classification system. Before and after operations, the intraocular conditions, visual acuity, corneal thickness and operative complications were recorded. The time of follow-ups was more than 6 months.

The operations were accomplished in 28 eyes and were changed into Phacoemulsification in 24 eyes. Posterior capsule rupture occurred in 2 cases (3.8%). Severe corneal edema was found in 3 cases (5.8%) that disappeared in 1 to 2 weeks. Preoperative visual acuity was < 0.05 in 19 cases, 0.05-0.3 in 28 cases and 0.4-0.5 in 5 cases. Postoperative visual acuity was ≤0.3 in 1 case, 0.4-0.5 in 12 cases, 0.6-0.9 in 25 cases and ≥1.0 in 14 cases. The mean values of pachymetry was 0.59 mm preoperatively and 0.60 mm in 3 months postoperatively (P = 0.097).

Photolysis using Dodick-ARC Nd: YAG laser system is a safe and effective method for cataract surgery. The further improvement of equipments and surgery techniques is needed.

To investigate the effects of various concentrations of taurine on streptozotocin (STZ)-induced diabetic cataracts in rats by biochemistry, radioimmunology and capillary zone electrophoresis (CZE).

One hundred Sprague-Dowley (SD) male rats, weight 180 ~ 200 g, were randomly divided into 5 groups: normal control, STZ plus saline, STZ plus 2% taurine, STZ plus 4% taurine and STZ plus 8% taurine groups. After being fasted for 12 hours, the rats of the STZ group (with or without taurine) were prepared by STZ intraperitoneal injection (55 mg/kg b. w.). Taurine-treated groups received 2%, 4% and 8% taurine injections once daily for 12 weeks (5 ml/kg b. w.). STZ group without taurine received a saline injection once daily for 12 weeks (5 ml/kg b. w.). During the experiment period, blood sugar was measured by ONE TOUCH® II. At the end of experiment, several biochemical parameters were measured by Beckman CX-7, insulin was measured by¹²⁵ I-insulin radioimmunological detecting kit and the level of taurine in the aqueous humor and the lens was measured by Beckman 5500 capillary zone electrophoresis (CZE) model.

Three weeks after the administration of STZ, the lenses showed vesicle and light opacity in the STZ group. Taurine suppressed the occurrence of early stage cataract obviously. Four to 12 weeks after the administration of STZ, the lens opacity in the 4% and 8% taurine treatment groups was markedly delayed as compared with that of the STZ group. The level of blood glucose in the 4% and 8% taurine groups was decreased evidently compared to that of the STZ group on 4 days, 4 weeks, and 8 weeks (the 4% taurine group). No difference could be detected between the STZ group and taurine treatment groups in 12 weeks. In the 4% and 8% taurine groups, the level of triglycerides decreased markedly compared to that of the STZ group and was near that of the control group. There were no differences of other biochemical parameters among all groups. In the 8% taurine group, the level of taurine in the aqueous humor and lens was increased obviously compared to that of the STZ group (P = 0.036 or P = 0.000, respectively).

The intervening effect of taurine on STZ-induced diabetic cataract is dose-dependent. This effect is not only related to decreases in the levels of blood sugar and triglycerides, but is also related to an increase in the taurine level in the aqueous humor and lens of diabetic rats, which enables the lens to escape from oxidant injury.

To investigate the approaches and effect of pure retinal photoreceptor cells and mixed retinal cells subretinal transplantation on retinal degenerative diseases.

16 Kunming mice were divided into two groups: group A and group B (n = 8). Through sclera and choroid, mixed retinal cells were injected into the subretinal space of mice eyes of group A and pure retinal photoreceptors were injected into the subretinal space of mice eyes of group B by using a specific micro-syringe under operative microscopy. 30, 90 and 180 d after transplantation, experimental eyes were enucleated, stained with HE and analyzed by light microscopy.

Most transplants (13/15) were exactly in host subretinal space without the infiltration of inflammatory cells and interfere of retina. The infiltration of inflammatory cells and damage of retina were only found in few eyes (2/15). The transplanted retinal cells survived well at 180 days after transplantation. The mixed retinal cells all formed rosette, but the pure retinal photoreceptors formed an orderly layer of photoreceptors.

This specific technique of subretinal microinjection is an easy, safe and optimal technique to meet the need of subretinal drug administration and retinal cells transplantation for retinal degenerative diseases. It is easier for the transplanted pure retinal photoreceptor cells to establish functional connection with host cells through subretinal microinjection.

To explore the characteristics of optic neuropathy and retinopathy subsequent to radiotherapy of nasopharyngeal carcinoma (NPC).

Sixty-eight eyes from 34 patients with fundus disease and visual disturbance after NPC radiotherapy were studied by vision testing, fundus examination, fundus fluorescein angiography (FFA) and computer analysis of visual field.

There were two types of fundus diseases: optic neuropathy and retinopathy. The former mainly showed edema, pale and atrophy of the optic disc. The latter showed mainly cotton-wool spots, bleeding, abnormal vessels or maculopathy of the retina. In 65.7% (22/34) of the patients fundus disease and visual disturbance occurred within 3 years after radiotherapy. FFA revealed that 88.1% (59/67) of the cases showed intense fluorescence, 65.7% of the cases (44/67) showed extensive flaw on macula, 71.9% of the cases (53/67) showed microaneurysm, and 53.7% of the cases (36/67) showed lack of perfusion of the retinal capillary network. Visual field test showed quadrant defect and irregular scotoma.

Early damage of the fundus subsequent to radiotherapy of NPC is the occlusion of capillary vessels or microcirculation, followed by occlusion of the small artery or vein, which causes chronic anoxemia on the optic disk, the macula, and the retina. The atrophy of the optic nerve, ischemic maculopathy, and retinal neo-vascular membrane may cause hemorrhage in the vitreous and retinal detachment, which can result in blindness. These changes are similar to the changes of ischemic optic neuropathy and diabetic retinopathy, which might offer a clue about the prevention and treatment of fundus damage subsequent to radiotherapy of NPC.

To investigate the antiproliferative effect of different concentration of all-trans retinoic acid (atRA) in a drug delivery system (DDS) in an experimental proliferative vitreoretinopathy (PVR) model.

The PVR animal model was induced by central vitrectomy and homologous fibroblasts injected at the same time in pigmented rabbits. Fifty rabbits underwent the surgery. These rabbits were divided into 5 groups of 10 rabbits at random. Group A was the control group. In group B, C, and E, one DDS device was implanted into the vitreous cavity after the vitrectomy, each DDS contained atRA 420 μg, 650 μg and no drug, respectively. In group D, two DDS devices were placed into the vitreous cavity, the total atRA content was 1 070 μg (420 μg + 650 μg). Each group was observed for 8 weeks. The development and the severity of PVR were observed and recorded. The vitreous cavity fluid was aspirated each week for measurement of the concentration of the atRA, in order to estimate the relationship between PVR and concentration of atRA. After 8 weeks, the retinal toxicity was evaluated by histopathology. Statistical analyses were performed at the end of the experiment.

Eight weeks after the operation, the incidence of PVR was lower in group C and group D, and there was a significantly statistical difference between these two groups and other groups. No intraocular toxicity was found by the histopathology examination.

atRA DDS is a safe and convenient mode for intraocular administration. DDS containing 650 μg and 1 070 μg atRA can inhibit the cell proliferation in the vitreous cavity effectively after surgery. atRA at a lower concentration cannot eliminate the cell proliferation but may delay the occurrence of PVR.