Refractive lens exchange for correction of high myopia.

PURPOSE: To evaluate the efficiency and safety of refractive lens exchange for the correction of high myopia. METHODS: We made a prospective study of the results of refractive lens exchange in 72 eyes that had undergone this surgical procedure between January 1996 and January 2001. Lens extraction by phacoemulsification was done by one surgeon on 34 patients. Follow-up was five months to five years (mean 48 months). The postoperative refractive target was emmetropia or a low degree of myopia. We compared pre- and postoperative uncorrected visual acuity, and preoperative best-corrected visual acuity with postoperative uncorrected visual acuity. Intra- and postoperative complications were recorded. RESULTS: In 72.2% of the eyes best-corrected visual acuity (BCVA) was > or = 0.5 before surgery. Four years after refractive lens exchange, uncorrected visual acuity (UCVA) was > or = 0.5 in 58.3% of eyes, and the proportion of eyes with BCVA > or = 0.5 increased to 83.3%. The sphere was fully corrected in 70.8% of cases, remained within 1.0 D of emmetropia in 87.5% and within 2.0 D of emmetropia in 95.8%. Posterior capsule opacification developed in 22 eyes (30.5%) and was treated with neodymium:YAG (Nd:YAG) laser capsulotomy. Cystoid macular edema with retinal detachment occurred in one eye. No wound leakage or eye infections were observed during five years' follow-up. CONCLUSIONS: Refractive lens exchange seems to be an effective alternative for the correction of high myopia, helping people over 40 years of age regain their distant vision.

Limbal-conjunctival autograft transplantation for recurrent pterygium.

PURPOSE: To assess the usefulness of limbal-conjunctival autograft transplantation (LCAT) for the treatment of recurrent pterygium. PATIENTS AND METHODS: Seventeen eyes with advanced recurrent pterygium underwent LCAT All had already been treated at least twice either by simple excision (n=15) or by conjunctival rotation autograft (n=2). Three eyes (17.65%) had symblepharon at the time of surgery, so LCAT was combined with amniotic membrane transplantation. The autograft was taken from the supero-lateral part of the same eye and transferred to the area where the pterygium had been excised. RESULTS: During 6-18 months of follow-up no postoperative complications occurred. In 15 eyes (88.24%) no pterygium recurrence was recorded; recurrence occurred in two eyes (11.76%) after 8 and 5 months. In three eyes with a combined symblepharon formation, remission of both pterygium and symblepharon growth was obtained. CONCLUSIONS: LCAT seems to be a promising and safe procedure for recurrent pterygium.

Profile of cytokines in aqueous humor from corneal graft recipients.

AIM: Due to the immune privilege of the anterior eye chamber, the success rate of corneal transplantation can reach 90%. The aim of this study was to determine cytokine profile in aqueous humor of patients undergoing corneal transplantation, and to establish whether cytokine profile at the time of surgery influenced corneal graft outcome. METHODS: Proinflammatory (TNF-beta and IFN-gamma) and immunosuppressive (TGF-beta2) cytokine levels were measured in aqueous humor and serum of 44 patients. Non-inflammatory corneal diseases included keratoconus (n=8), bullous keratopathy (n=7), and stromal dystrophy (n=3). Inflammatory diseases included corneal scars (n=10), graft rejection (n=5), pending perforation (n=4), chemical burns (n=4), rejection/ uveitis (n=1), infectious keratitis (n=1), and perforated ulcer (n=1). Control aqueous humor and sera were obtained from cadavers without corneal pathology. RESULTS: The concentration of TGFbeta2 in the aqueous humor in non-inflammatory corneal diseases was similar to that of controls (2,605+/-204 pg/mL vs 2,200+/-100 pg/mL). In inflammatory corneal diseases, the concentration of TGFbeta2 in aqueous humor was significantly lower (1,400+/-375 pg/mL, p<0.001). TNF-beta was detected in the aqueous humor of 16 out of 26 patients with inflammatory corneal diseases and in all patients with stromal dystrophies, but was undetectable in cases of keratoconus and bullous keratopathy. Low levels of IFN-gamma were present in all aqueous humor samples. Patients' sera contained significantly less cytokine (up to 252 pg/mL) then their aqueous humor (p<0.001). We have set an arbitrary cut-off point for TGF-beta2 level in aqueous humor at 1,500 pg/mL and divided all investigated samples (from 44 patients and 10 controls) into two groups, one with high and the other with low TGF-beta2 concentration. The coefficient of contingency showed that patients with high TGF-beta2 concentration in their aqueous humor had significantly greater chance for graft acceptance than those with low TGF-beta2 concentration (p<0.001). CONCLUSION: High TGFbeta2 concentrations in the eyes without intraocular inflammation suggest its immunosuppressive role in human eyes. High concentration of TGFbeta2 (>1,500 pg/mL) was associated with graft acceptance. Also, absence of proinflamatory TNFbeta increased the graft acceptance, but independently from TGFbeta2.

The role of HLA-DRB1 matching in corneal grafting.

The aim of the study was to evaluate the role of HLA-DRB1 (Human Leukocyte Antigens) matching in corneal transplantation. Fifty-two patients were observed. Low-risk group consisted of 28 patients and high-risk group consisted of 24 patients. All the patients and donors were tissue typed with Polymerase Chain Reaction (PCR) on the HLA-DRB1 gen. The primary corneal disease preceding keratoplasty was keratopathia (15), leucoma (10), keratoconus (7), Re-KPP (6), impending perforation (4), combustio corneae (3), degenerative disorders (2), keratoglobus (1), keratouveitis (1), corneal maculae (1), and corneal melting syndrome (1). The graft rejection frequency was higher in the group of high-risk patients (29%) than in the group of low risk patients (7.1%). The rejection rate of compatible grafts was 37% for high risk and 2% for low risk group, while the rejection rate of incompatible was 44% in high risk and 5% in low risk group. We can conclude that HLA-DRB1 matching does not improve corneal graft survival.

Corneal transplantation in children.

The main purpose of the study was to describe the surgical success rate and visual results of penetrating keratoplasty in children. This retrospective study included children that underwent corneal transplantation at the Department of Ophthalmology, General Hospital "Sveti Duh", in the period 1994-1999. Patients' age ranged from 6 to 16 years. Twenty-five corneal transplants were performed in 24 eyes. Corneal pathologies were corneal leucoma, congenital dystrophy, corneal combustion, corneal scar after perforating injury, keratoconus, corneal melting, hematocornea and rekeratoplasty. The follow-up period was at least 6 months. The rate of graft survival was 1 year in 75% of eyes with congenital dystrophy and keratoconus. Hematocornea and rekeratoplasty ended with graft failure. Postoperative visual acuity improvement was recorded in 14 out of 25 eyes. Penetrating keratoplasty in children showed very good surgical success. The final visual outcome was affected by irreversible amblyopia.

Multilayer vs. monolayer amniotic membrane transplantation for deep corneal ulcer treatment.

The purpose of the study was to evaluate the efficacy of multilayer amniotic transplantation (AMT) for reconstruction of corneal stroma and epithelium. Corneal ulcer (28) was a consequence of a previous infectious or neurotrophic keratitis. In the first group (17) ulcer was covered with monolayer AM, while in the other group (11) there were two or more layers of AM situated in the ulcer and the whole cornea was covered with AM sheet. Monolayer AMT was successful in 64% while the multilayer AMT success rate was 72%. AM gradually dissolved within 3-6 postoperative weeks. AM transplantation facilitates rapid healing of corneal epithelium, reduces inflammation and stimulates epithelial cell regrowth. In eyes with deep corneal ulcer multilayer technique proved to be better then monolayer procedure.

Pterygium treatment with limbal-conjunctival autograft transplantation.

The objective of this pilot study was to examine the usefulness of limbal autograft transplantation (LCAT) in the treatment of recurrent pterygium. Eleven eyes with advanced recurrent pterygium underwent LCAT. All eyes were previously treated at least two times either by simple excision (10) or conjunctival rotation autograft (1). In two eyes (18.18%) symblepharon was present at the time of surgery, therefore LCAT was combined with amniotic membrane transplantation. Limbal-conjunctival autograft was taken from supero-lateral part of the same eye and transferred to the area where pterygium was excised. No intraoperative complications occurred. In ten eyes (90.9%) no pterygium recurrence was recorded during the follow-up time, and one (9.1%) recurrence was recorded after 5 months. In two eyes with combined symblepharon formation remission of both pterygium and symblepharon growth was obtained. LCAT proved to be a promising and safe procedure in recurrent pterygium treatment.

Topical soluble tumor necrosis factor receptor type I suppresses ocular chemokine gene expression and rejection of allogeneic corneal transplants.

OBJECTIVE: To determine the effect of topical soluble tumor necrosis factor receptor type I (sTNFR-I) on survival of murine orthotopic corneal transplants and on ocular chemokine gene expression after corneal transplantation. METHODS: BALB/c mice (N = 50) were used as recipients of multiple minor H-disparate corneal transplants from B10.D2 donors. After orthotopic corneal transplantation, mice were randomized in a masked fashion to receive either topical sTNFR-I or vehicle 3 times daily, and all grafts were evaluated for signs of rejection and neovascularization by slitlamp biomicroscopy for 8 weeks. Ocular chemokine gene expression in sTNFR-I- and vehicle only-treated groups was determined using a multiprobe ribonuclease protection assay. RESULTS: Hosts treated with topical sTNFR-I experienced significantly enhanced corneal allograft survival compared with animals treated with vehicle alone (P =.01). Moreover, postoperative messenger RNA levels of RANTES and macrophage inflammatory protein-1beta in sTNFR-I-treated eyes were substantially suppressed compared with vehicle-treated eyes. Vehicle-treated eyes bearing rejected allografts expressed higher levels of messenger RNA for both chemokines than control eyes bearing accepted allografts. CONCLUSIONS: Topical treatment with sTNFR-I promotes the acceptance of allogeneic corneal transplants and inhibits gene expression of 2 chemokines (RANTES and macrophage inflammatory protein-1beta) associated with corneal graft rejection. CLINICAL RELEVANCE: Our findings support the feasibility of a topical anticytokine strategy as a means of reducing corneal allograft rejection without resorting to the use of potentially toxic immunosuppressive drugs.

Prevention of allergic eye disease by treatment with IL-1 receptor antagonist.

PURPOSE: To determine the impact of interleukin-1 (IL-1) inhibition using IL-1 receptor antagonist (IL-1Ra) in a mouse model of allergic eye disease. METHODS: A/J mice sensitized and challenged with cat dander in the eye were treated with topical IL-1Ra or vehicle alone. Control mice were treated with IL-1Ra or vehicle but sensitized and challenged with phosphate-buffered saline alone. Immediately after the final allergen challenge, the mice were observed for behavioral changes and assessed for lid injection and chemosis. The animals were then killed, eyes and attached lids were removed for either RNA extraction or histology, and draining lymph nodes were removed for either RNA extraction or in vitro stimulation assays. Differences in chemokine message between experimental and control groups-were determined by RNase protection assays. RESULTS: Treatment with IL-1Ra in allergen-challenged animals significantly reduced allergen-induced changes in photosensitivity (60%, P = 0.0002), chemosis (50%, P = 0.0151), and injection (86.7%, P = 0.0068) compared with vehicle-treated controls. Interleukin-1Ra reduced the number of degranulated mast cells and caused a significant reduction in the number of eosinophils infiltrating the conjunctival matrix (P<0.001) after allergen challenge. Examination of chemokine mRNA taken from the conjunctiva and draining lymph nodes by RNase protection assay showed a profound decrease in the production of a number of C-C chemokines. CONCLUSIONS: These findings suggest that IL-1Ra is suppressing allergic eye disease by a down-modulation of the recruitment of eosinophils and other inflammatory cells essential for the immunopathogenesis of ocular atopy.

Effect of topical interleukin-1 receptor antagonist (IL-1ra) on corneal allograft survival in presensitized hosts.

PURPOSE: Topical interleukin-1 receptor antagonist (IL-1ra) promotes corneal allograft survival in naive hosts by suppressing local antigen-presenting cell function and allosensitization. The purpose of these experiments was to test whether IL-1ra could likewise promote transplant survival in pre-sensitized hosts. METHODS: Orthotopic corneal grafts were performed into immunized (N = 65) and naive (N = 40) BALB/c recipients from fully disparate (C57BL/6) or minor H-only disparate (B10.D2) mice. Allograft recipients were randomized to receive treatment with IL-1ra or vehicle only. RESULTS: Immunization to both MHC and minor H alloantigens was associated with accelerated graft rejection. IL-1ra treatment had no significant impact on overall graft longevity or the early incidence of graft rejection in pre-immunized recipients of fully-disparate corneal allografts (P = 0.25). Similarly, although rejection of corneal grafts in hosts immunized to minor H alloantigens occurred more slowly in mice treated with IL-1ra than in controls (P = 0.04), overall graft survival at 8 weeks was comparable (P = 0.07) among the two groups. CONCLUSIONS: The accelerated rejection of corneal allografts in presensitized hosts is not materially affected by IL-1ra, particularly if the host has been immunized to donor MHC alloantigens. These data confirm that the role of IL-1ra in corneal transplantation is primarily limited to downmodulating the afferent, not expression, arm of alloimmunity.

Early expression of proinflammatory cytokines interleukin-1 and tumor necrosis factor-alpha after corneal transplantation.

This study's aim was to determine the early postoperative expression of proinflammatory cytokines interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) by corneal grafts. BALB/c (n = 90) and C57BL/6 (n = 90) murine recipients were grafted with donor corneas from either syngeneic or allogeneic mice. At 7 and 14 days after surgery, corneal grafts were excised and the recipient rims separated from the donor tissue. Corneal segments were cultured and assayed for cytokines by enzyme-linked immunosorbent assay (ELISA). There was profound upregulation in expression of both IL-1alpha and TNF-alpha after corneal transplantation. Among both low-rejecting BALB/c and high-rejecting C57BL/6 hosts, levels of IL-1alpha were significantly (p < 0.01) more marked in allogeneic as compared to syngeneic grafts. TNF-alpha overexpression was similarly more marked in allogeneic as compared to syngeneic grafts in both BALB/c and C57BL/6 hosts, although the difference was generally more marked among high-rejecting C57BL/6 recipients. In the case of both IL-1alpha and TNF-alpha, the principal source of cytokine expression in the transplanted tissue was the recipient rim. There is significant overexpression of both IL-1alpha and TNF-alpha during the first 2 weeks after transplantation in both syngeneic and allogeneic orthotopic corneal grafts. However, whereas in syngeneic grafts cytokine expression generally decreases after the first postoperative week, significantly elevated cytokine levels are sustained in allogeneic grafts, implicating IL-1 and TNF-alpha as mediators of the alloimmune response in corneal transplantation.

TNF-alpha regulates corneal Langerhans cell migration.

Langerhans cells (LC) belong to the dendritic cell family and mediate Ag presentation in the cornea and ocular surface. Under normal physiological conditions, the central cornea is devoid of LC. Centripetal migration of LC plays a critical role in promoting immunoinflammatory responses in the eye including allograft rejection and herpetic keratitis. The molecular mechanisms responsible for ocular LC migration are poorly understood. To examine whether TNF-alpha mediates corneal LC migration and to establish the interaction of IL-1 and TNF-alpha in regulating LC migratory capacity, we utilized gene-targeted knockout mice lacking IL-1 receptor I (IL-1RI-/-), TNF receptor I (p55-/-), TNF receptor II (p75-/-), or both (p55-/-p75-/-). LC migration was induced by thermal cautery or cytokine injection and enumerated by an immunofluorescence assay. Migration of LC after cauterization and TNF-alpha injection was significantly depressed in both p55-/- and p75-/- mice. Similarly, in the first 72 h after intracorneal injection of IL-1alpha, LC migration was reduced in p55-/-, p75-/-, and p55-/-p75-/- mice. In contrast, injection of TNF-alpha in IL-1RI-/- mice led to normal migration of corneal LC indistinguishable from wild-type controls. These results suggest that the IL-1 induction of corneal LC migration is largely mediated by TNFR function, whereas TNF-alpha induction of LC migration is independent of IL-1RI activity. Moreover, the data suggest that both p55 and p75 signaling pathways are important in mediating LC migration in the cornea.

The influence of tissue culture on corneal immunogenicity.

In this study we examined whether immunization with heterotopic corneal graft can be suppressed by usage of cultured corneal tissue. Starting from the hypothesis that the corneal antigenicity might change during long-time storage, we compared, in a mouse model, the immunization obtained with fresh and> stored corneas. Heterotopic (chest wall) mice corneal allografts were exchanged between donors and hosts: (1) mismatched at multiple minor H loci and (2) only H-Y mismatched animals. Median survival time (MST) of primary and secondary skin grafts exchanged between mentioned donors and hosts was recorded. Recipient mice were immunized with either: (a) tail-skin graft, (b) fresh cornea graft or (c) corneal graft stored for three weeks in tissue culture. Three weeks later, recipients were challenged with skin graft placed at the opposite side of the chest wall and MST of these skin grafts was recorded. MST of secondary skin grafts in animals that had been immunized by skin served as a control. In case of multiple minor H disparity, MST of a first-set skin graft was 12 days, as compared to 9 days in case of secondary skin graft (P<0.05). MST of secondary skin graft following immunization by both fresh and stored corneas was 10 days. These data suggest that stored corneas don't loose ability to sensitize the multiple minor H disparate host. It also show that both cultured and fresh corneas, when placed in non-privileged site, have same immunizing capacity as skin (MST of 10 and 9 days, respectively; P>0. 1). When only H-Y disparate animals were used, MST of a first-set skin grafts was 26 days and of secondary skin graft 11 days (P<0.01). In case of H-Y disparity, MST obtained after immunization with fresh and stored corneal tissue (19 and 18 days, respectively) was significantly longer as compared to skin (P<0.05). However, no significant difference in MST of secondary skin grafts between recipients of fresh (19 days) and stored corneal grafts (18 days) was recorded. According to our results, the ability of corneal tissue to immunize both multiple minor H mismatched, as well as only H-Y mismatched host, was not influenced by storage in a tissue culture.

Human amniotic membrane in the reconstruction of the ocular surface.

We sought to determine the efficacy of amniotic membrane transplantation (AMT) in the reconstruction of ocular surface. AMT was performed on 40 eyes with following indications: I, persistent corneal ulceration (n = 12); II, impending perforation (n = 6); III, persistent epithelial defect on the corneal graft (n = 6); IV, recurrent pterygia (n = 10), and V, risk of conjunctival scarring (n = 6). Amniotic membrane was prepared from a fresh placenta under sterile conditions, washed with BSS containing penicillin, streptomycin, neomycin and amphotericin B and stored at -80 degrees C in 1:1 InoSol:Glycerol solution. Donor serological test for HIV, HBV and HCV were all negative. Associated surgical procedures according to indication were performed. Healing of the corneal ulcer in Group I was obtained in 67% of eyes at 1-3 weeks after surgery, Group II: AMT was followed by 'a chaud' keratoplasty in 33% and by planned keratoplasty in 67% patients, Group III: healing of the defect in 33% of eyes in 2-5 postoperative weeks, Group IV: no recurrence of pterygium ingrowth in 70% in the follow up period of 6-14 months, and V: 84% of patients had good eye motility without any synechia formation. We concluded that AMT have shown to be effective in enhancing healing of the corneal defects, in prevention of symblepharon formation and recurrent pterygium ingrowth. In case of impending perforation, AMT alone was not a method of treatment but is useful as a first step procedure in preparing the eye for the corneal transplantation.

Hydrogen peroxide modulation of the superoxide anion production by stimulated neutrophils.

Hydrogen peroxide (H2O2) pretreatment of human neutrophils results in a suppression of the superoxide anion (O2) production in response to surface-acting stimulants such as lipopolysaccharide (LPS) and opsonized zymosan. This effect was not observed when phorbol myristate acetate (PMA), formyl-methionyl-leucyl-phenylalanine (fMLP) or tumor necrosis factor alpha (TNF alpha) were used as a stimuli. Since the response to PMA and other stimuli was unimpaired by preincubation with H2O2, we assume that the H2O2 modulated O2 production is probably due to alteration of the LPS receptor conformation rather than effecting directly NADPH-oxidase. The balance of reactive oxygen species (ROS) produced by neutrophils in the state of sepsis may thus be autoregulated by negative feedback phenomena of locally produced H202.

Timing of cataract surgery in diabetics.

In their retrospective study, the authors investigated the outcome of extracapsular cataract extraction (ECCE) followed by posterior chamber intraocular lens implantation (PCIOL), in 2864 operated eyes, out of which 546 (19%) were in diabetics. The preoperative retinal status was recorded in all subjects. In 6 (1%) patients, laser photocoagulation was performed preoperatively. The obtained visual acuity was 0.4 or better in 90.0% of diabetics and in 91.8% of control subjects, showing no significant difference in the postoperative complications between diabetics and non-diabetics. The results indicated the cataract operation (ECCE + PCIOL) to be a well tolerated surgical procedure in diabetic patients with lenticular opacity, in whom it should be even earlier performed than in nondiabetics, because cataract prevents the diagnosis or treatment of a suspect retinal disorder.

Complications following two methods of posterior chamber intraocular lens suturing.

The aim of this study is to compare complication rates in two different operative techniques applied for the secondary, posterior chamber intraocular lens (PCIOL) implantation with sulcus fixation. 179 eyes with partial or no posterior capsule support underwent surgery. Applied techniques were: transscleral fixation of the IOL by passing with the fixation needle through the sulcus from the inside (70 eyes) or from the outside (109 eyes) of the bulbus. The most frequent intraoperative complications were haemorrhages and vitreous prolaps with no significant difference between used techniques. In the 'from the inside' group, following late postoperative complications developed: astigmatism of > 4D (24%), cystoid macular oedema (20%), pupil distortion (14%), partial posterior capsule opacification (10%), suture exposure (10%), IOL decentration (8%) and hemophthalmus (3%). In the 'from the outside' group same complications showed a decreased rate: 17%, 16%, 8%, 8%, 9%, 5% and 1%, respectively. Other late complications like high intraocular pressure, synechiae and uveitis were adequately represented in both techniques. After 24 months follow-up, best corrected visual acuity > or = 0.8 was achieved in 48.5% of eyes when 'from the inside' and in 57.7% of eyes when 'from the outside' technique was used.

Triple procedure 'a chaud'.

Although it is widely accepted that acute uveitis is the main contraindication for intrabulbar procedures, conditions in the presented group of 24 patients (mean age 63 years, ranging from 35 to 74) required immediate surgery. The corneal pathologies included: perforated corneal ulcer in 12, imminent corneal perforation in ten and corneal melting syndrome in two patients. Partial perforative keratoplasty was accompanied by various combinations of surgical procedures, depending on the preoperative status. In cases of aphakia (N = 5) and anterior chamber pseudophakia (N = 5) secondary PCIOL implantation with sulcus fixation was performed, combined with ACIOL explanation in the latter group. The largest group included patients with complicated cataract (N = 14), where classic triple procedure was performed in ten patients. In three patients, the surgery had to be completed with sulcus fixation of the PCIOL, due to posterior capsule rupture. Associated glaucoma in one patient required trabeculectomy along with triple procedure. Postoperative complications that could not be treated with conservative measures for subsequent corneal decompensation, required rekeratoplasty in three (12.5%) patients. Visual acuity amelioration, ranging from 0.2-0.8, was achieved in seven (29.2%) and nine (37.5%) patients after 3 and 6 months, respectively.