Clinical evaluation of the model AT-45 silicone accommodating intraocular lens: results of feasibility and the initial phase of a Food and Drug Administration clinical trial.

OBJECTIVE: To evaluate the clinical outcomes in cataract patients after implantation of an accommodating intraocular lens, designed to move forward and backward along the visual axis. DESIGN: Prospective, noncomparative case series. PARTICIPANTS: Sixty-two patients scheduled for small-incision, extracapsular cataract extraction by phacoemulsification. METHODS: Twenty-eight eyes of 14 patients in the feasibility phase of the study and 48 eyes of 48 patients in the next phase of study underwent cataract extraction and implantation of the AT-45 accommodating intraocular lens. Prospective follow-up was analyzed at 1 month after surgery and compared with baseline characteristics 1 month and 3 to 6 months after surgery. MAIN OUTCOME MEASURES: Postoperative distance (uncorrected and best corrected), near (uncorrected, through the distance correction, best-corrected, i.e., with add), and intermediate (through the distance correction) visual acuity. RESULTS: All patients with monocular pseudophakia had best-corrected distance visual acuity of 20/40 or better. Patients with bilateral pseudophakia had best-corrected visual acuity of 20/25 or better when tested binocularly. The results from 28 eyes of 14 patients participating in the feasibility study were combined with those from 48 eyes of 48 patients included in the next phase of the AT-45 study. Uncorrected distance visual acuity was 20/40 or better in most patients (90%, or 56 of 62 eyes implanted and available for follow-up). Ninety-seven percent of patients (60/62) had uncorrected near visual acuity of 20/30 or better. Forty-eight eyes had intermediate visual acuity measured at 28 inches without 'add', and 44 of them (92%) achieved 20/30 or better. No complications or adverse events were reported. CONCLUSIONS: The AT-45 accommodating intraocular lens, designed to allow movement along the visual axis of the eye by using the natural physiology of the intact ciliary muscle after cataract removal, provides patients with excellent uncorrected distance, intermediate, and near visual acuity and should be considered as a modality to allow the majority of pseudophakic patients to see at all distances without glasses.

Anatomic factors affecting microkeratome placement in laser in situ keratomileusis(2)(2).

PURPOSE: To identify the significant anatomic factors that affect placement of 2 microkeratomes and compare the ease of their placement. SETTING: The Laser Center, Houston, Texas, USA. METHODS: Anatomic factors affecting microkeratome placement were evaluated in 250 eyes of 137 myopic patients in a prospective consecutive-enrollment study. Anatomic factors measured included vertical orbital width, horizontal interpalpebral fissure (HPF), corneal diameter, and position of the corneal apex relative to the lateral orbital rim (PCL). Vertical orbital width and HPF were measured with a micrometer caliper (Mitutoyo); corneal diameter, with Orbscan topography (Bausch & Lomb Surgical); and PCL, with a Hertel exophthalmometer. Patients were randomly divided into 2 groups (125 eyes/group) to have surgery with the Automated Corneal Shaper((R)) (ACS) (Bausch & Lomb Surgical) or Hansatome (Bausch & Lomb Surgical) microkeratome. Microkeratome placement was graded by 1 surgeon as "easy" (grades 1, 2, and 3) or "difficult" (grades 4 and 5). Results were correlated with anatomic factors to evaluate possible anatomic influences on the difficulty of microkeratome placement. RESULTS: The PCL and vertical orbital width were statistically significant factors in predicting the difficulty of ACS microkeratome placement (P <.05). For the Hansatome microkeratome, since only 1 eye was graded as a difficult placement, the anatomic parameters affecting placement could not be evaluated. There were no statistically significant between-group differences in mean age and means of all anatomic factors measured (independent t test, P >.05). Difficult applanations were encountered in the ACS group (8/125 eyes, 6.4%) more than in the Hansatome group (1/125 eyes, 0.8%), which was a statistically significant difference by the Pearson chi-square test (P <.05). CONCLUSIONS: The PCL and vertical orbital width were significant anatomic factors affecting placement of the ACS microkeratome. The anatomic factors affecting Hansatome microkeratome placement could not be determined. The percentage of difficult placements was significantly lower with the Hansatome than with the ACS.

Diffuse lamellar keratitis related to endotoxins released from sterilizer reservoir biofilms.

OBJECTIVE: To investigate the risk factors and control mechanisms used to control the outbreak of diffuse lamellar keratitis (DLK) associated with laser in situ keratomileusis (LASIK) and examine the relationship between DLK and endotoxins released from sterilizer biofilm reservoirs. DESIGN: Clinic-based cohort and laboratory study. PARTICIPANTS: All patients undergoing LASIK at our clinic from October 7, 1998 through August 31, 1999. The case definition was a diffuse infiltrate in the interface developing within the first week after surgery. INTERVENTIONS: Biofilm control in the sterilizer, changes in sterilizer, distilled water, instruments, and irrigating fluids. MAIN OUTCOME MEASURES: The incidence of DLK after LASIK surgery. RESULTS: There were 983 evaluable patients, with three whose DLK status was not recorded. There were 52 cases of DLK. Burkholderia pickettii was isolated from the sterilizer reservoir. Potential risk factors and associations, for which there was no significant difference, included age and sex of the patients, surgeon, operating suite temperature or humidity, drapes used, saline solutions used, time of day the surgery was performed, and microkeratome use. Sterilizers 1 and 2, before biofilm control, were compared with sterilizer 3, after control. The relative risk was 9.4 (confidence limits [CL], 7.5-11.8) for sterilizer 1 versus 3 and 18. 7 (CL, 11-32) for sterilizer 2 versus 3. Three cases occurred after biofilm control, but were sporadic in nature and associated with epithelial defects. CONCLUSIONS: Clusters of DLK may be related to endotoxins released from gram-negative biofilms in sterilizer reservoirs. We experienced an outbreak of DLK affecting 52 patients and isolated B. pickettii from the sterilizer reservoir. Epidemiologic investigation showed that biofilm control in the sterilizer reservoirs was associated with a significant reduction in the development of DLK. We encourage any clinics that experience a cluster of DLK to consider microbiologic and epidemiologic investigation for the effectiveness of sterilizer biofilm control.

Draping technique to isolate lashes and achieve maximum exposure.

A surgical draping technique is presented that decreases surgical time, maximizes surgical site exposure, and decreases the risk of infection. It was also designed to enhance patent comfort.

Corneal endothelial changes after divide and conquer versus chip and flip phacoemulsification.

PURPOSE: To evaluate changes in central corneal endothelial cells and corneal thickness after divide and conquer phacoemulsification and chip and flip phacoemulsification. SETTING: Houston Eye Clinic, Houston, Texas, USA. METHODS: Forty-four eyes were randomly assigned to one of two groups to have divide and conquer (D/C Group) or chip and flip (C/F Group) phacoemulsification with implantation of a posterior chamber, foldable, silicone intraocular lens performed by one surgeon. Of these, 41 eyes of 37 patients (22 D/C Group, 19 C/F Group) met the inclusion criteria. All surgeries were uneventful. A complete eye examination including specular microscopy and pachymetry was performed preoperatively and 1 week and 1 and 3 months postoperatively. RESULTS: There were no significant between-group differences in any of the following means: sex; age; time at 70% phaco power; total phacoemulsification time. No correlation was found between ultrasound time and increased corneal thickness except for a significant increase in percentage of hexagonal cells in the C/F Group at 1 month. The only statistically significant between-group differences were greater endothelial cell loss in the C/F Group at 1 month and the percentage change in hexagonal cells at 1 week (1.1% increase, D/C Group; 10.7% decrease, C/F Group). CONCLUSION: The divide and conquer technique led to less endothelial loss and hexagonal cell change than the chip and flip technique, although at 3 months the differences were not significant.

Ocular integrity after refractive procedures.

PURPOSE: The purpose of the study was to determine the integrity of human eyes after refractive procedures. METHODS: Whole human globes underwent either radial keratotomy (RK) with eight incisions, automated lamellar keratoplasty (ALK), photorefractive keratectomy (PRK), or excimer laser assisted in situ keratomileusis (LASIK). Eyes then were subjected to quantitatively increasing levels of trauma until rupture occurred. RESULTS: All eyes operated on required less energy to rupture as compared with that of control eyes. The mean number of trials required for rupture is as follows (energy doubled with each successive trial): normal, 4.29; LASIK, 3.80; ALK, 3.67; PRK, 3.60; and RK, 2.83. The level of energy required to rupture normal, ALK, PRK, and LASIK eyes was not significantly different. All RK eyes ruptured at incisions. Most ALK, PRK, and LASIK eyes ruptured near the flap edge or limbus. Most normal eyes ruptured with both corneal and scleral involvement. Age of tissue donors at the time of death and time elapsed between death and procedure were not significantly different between groups (P = 0.88 and 0.79, respectively). CONCLUSIONS: The energy required to rupture ALK, PRK, and LASIK eyes is not significantly different from that for normal eyes. The RK eyes ruptured with significantly less energy than did normal eyes. All RK eyes ruptured at incision sites.

Differential phosphorylation of the beta2 integrin CD11b/CD18 in the plasma and specific granule membranes of neutrophils.

Neutrophil aggregation is mediated by the beta2 integrin CD11b/CD18, which has limited expression on the surface membrane of resting cells but is recruited from intracellular organelles after cell activation. We have previously found that CD11b/CD18 newly translocated to the plasma membrane does not contribute to adhesion but must be modified to be functional. Because neutrophil aggregation induced by phorbol myristate acetate (PMA) is accompanied by de novo phosphorylation of the CD18 cytoplasmic tail, we sought to determine whether CD11b/CD18 phosphorylation is separately regulated in the different cellular compartments. Accordingly, [32P]-labeled CD11b/CD18 was immunoprecipitated from purified neutrophil-specific granule or plasma membrane lysates. In plasma membrane fractions, as in whole cell lysates, CD18 became phosphorylated in cells exposed to PMA but not in untreated cells or cells treated with N-formyl-methionyl-leucyl-phenylalanine (fMLP). The alpha chain, CD11b, was phosphorylated under all conditions. In contrast, only marginal phosphorylation of specific granule-associated CD18 or CD11b was observed. Calyculin A, an inhibitor of serine/threonine phosphatases (pp1 > pp2a), induced strong phosphorylation of CD18 in the plasma membrane but not in the specific granules. Addition of intact specific granule membranes to the plasma membranes from PMA-treated neutrophils markedly decreased phosphorylation in both CD11b and CD18 subunits. These data suggest that the phosphorylation of CD11b/CD18, which accompanies neutrophil activation, is limited to plasma membrane-associated molecules. Phosphorylation, either constitutive or induced, is absent in the specific granule membranes. The difference may be due to a specific granule-associated phosphatase, probably distinct from ppl. Therefore adhesion-competent plasma membrane CD11b/CD18 and adhesion-incompetent specific granule CD11b/CD18 differ in their state of phosphorylation.

A comprehensive approach to LASIK.

Candidates for LASIK procedures should have a stable refraction for at least 12 months. The three main contraindications for LASIK include patients with keratoconus or autoimmune disease and active corneal or ocular disease. The proper laser room environment is critical for optimal laser performance. The temperature should be maintained between 18 degrees C and 24 degrees C, and the humidity should be kept below 50%.

Six-month results of the multicenter phase I study of excimer laser myopic keratomileusis.

We report six-month results of the Summit Technology Myopic Keratomileusis Phase I multicenter study. Fifty-seven eyes of 57 patients had keratomileusis to correct high myopia. A microkeratome was used for the primary keratectomy and the excimer laser was used to ablate the stroma of the resected lenticle (cap) or the stromal bed (in situ). At six months, 31 of the 47 eyes available for follow-up (65.9%) had uncorrected visual acuity of 20/40 or better; 16 (34.0%) had uncorrected acuity of 20/25 or better. Thirty-seven eyes (78.7%) maintained the same (+/- one Snellen line) best corrected visual acuity as before surgery; seven (14.9%) lost two lines and three (6.4%) lost more than two lines. In addition to the six-month multicenter study results, we report two year results in a subset of 28 eyes (22 from the multicenter study and six fellow eyes). At six months, 17 of the 24 eyes available for follow-up (70.9%) had uncorrected visual acuity of 20/40 or better and nine (37.5%) had uncorrected acuity of 20/25 or better, including eyes that had worse than 20/80 best corrected visual acuity preoperatively. At 24 months, five of the seven eyes available for follow-up (71.4%) had uncorrected acuity of 20/25 or better. Only one patient lost two lines of best corrected vision at six months and no patient lost more than two lines; at 24 months, all patients maintained (+/- one line) best corrected vision.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship between maternal and neonatal levels of antibodies to 48 kDa SSB(La), 52 kDa SSA(Ro), and 60 kDa SSA(Ro) in pregnancies complicated by congenital heart block.

OBJECTIVE: Since there is suggestive but, to date, indirect evidence that maternal anti-SSA(Ro) and SSB(La) antibodies are pathogenic in congenital heart block (CHB), we explored the hypothesis that binding to fetal tissues would result in selective depletion of autoantibodies from the neonatal circulation. METHODS: Maternal and umbilical cord levels of anti-48 kDa SSB(La), anti-52 kDa SSA(Ro) and anti-60 kDa SSA(Ro) antibodies were measured by ELISA and immunoprecipitation at parturition in 15 pregnancies complicated by CHB. A control group consisted of 13 pregnancies in which the mother was known to have antibodies to either SSA(Ro) and/or SSB(La) and the children did not have CHB. RESULTS: The ratios of maternal to cord serum levels of anti-48 SSB(La), anti-52 SSA(Ro) and anti-60 kDa SSA(Ro) antibodies ranged from 0.71 to 2.38 in both affected and unaffected pregnancies. The mean ratio obtained for each of the 3 autoantibodies was not significantly different between the 2 groups. Moreover these ratios did not significantly differ from the mean ratios obtained for total IgG levels in either group. CONCLUSION: These data demonstrate that maternal antibodies to all components of the SSA(Ro) SSB(La) system are efficiently transported across the placenta and are not selectively depleted in the circulation of neonates with CHB.

Autoantibody responses to the "native" 52-kDa SS-A/Ro protein in neonatal lupus syndromes, systemic lupus erythematosus, and Sjogren's syndrome.

Abs to the 52-kDa SS-A/Ro protein are found in high prevalence in patients with Sjogren's syndrome (SS) and mothers whose children have the neonatal lupus syndrome (NLS). This study further defines the specificity of this response. By ELISA, 97% of 59 mothers of offspring with NLS had Abs to the 52-kDa recombinant protein compared with 80% in 132 non-NLS sera with anti-SS-A/Ro Abs (p < 0.004). Antigenic regions on the 52-kDa protein were evaluated by immunoprecipitation of [35S]-radiolabeled in vitro translation products. Ninety-five percent of 99 sera that contained anti-52-kDa Abs by ELISA reacted with a large fragment spanning amino acids (aa) 1-291. Two antigenic regions were identified, aa169-291 containing the leucine zipper that was recognized by 83% of the anti-52-kDa sera tested and aa1-78 containing the zinc finger domains that was recognized by only half the sera. No sera immunoprecipitated this N-terminal fragment exclusively. Recognition of one or both regions was not unique to any clinical subset of patients; however, a greater number of sera from patients with SS contained both specificities, whereas asymptomatic mothers whose children had NLS comprised the only clinical group in which the majority recognized the central region of the molecule. Reactivity with both epitopes was demonstrated significantly more often in sera with high titers of Abs to the 60-kDa rSS-A/Ro protein by ELISA in association with the anti-52-kDa response compared with anti-52-kDa responses associated with low titers of anti-60-kDa Abs (p < 0.04). Eighty-one percent of 16 sera that recognized the N-terminal epitope were from patients with the combination of HLA-DRB1*0301, DQA1*0501, and DQB1*0201 alleles, compared with 30% of 10 that recognized only the central epitope (p < 0.02). In summary, this study demonstrates that there are at least two antigenic determinants on the 52-kDa SS-A/Ro protein, one "immunodominant" and the other recognized by a more "restricted" subset of anti-52-kDa SS-A/Ro Abs.

Intraoperative pachometry during automated lamellar keratoplasty: a preliminary report.

BACKGROUND: The hinge technique greatly improves the results of automated lamellar keratoplasty but makes it impossible to measure the thickness of the corneal cap with a micrometer. We developed a technique of measuring cap and stromal disc thickness with a pachometer and compared the results with those obtained with a micrometer. METHODS: Measurements of the thickness of the stromal disc and/or corneal cap were taken with the Mitutoyo micrometer and the Chiron Corneo-Gage System III pachometer in five myopic and three hyperopic cases undergoing automated lamellar keratoplasty with complete cap resection. The intended postoperative refraction was plano. Postoperative refractions were taken at two months. RESULTS: In most cases, the corneal cap measured thinner while the stromal disc measured thicker by the micrometer than by the pachometer because of the hydration status of the stromal bed. In both myopic and hyperopic cases, the thickness measurements taken with the pachometer correlated better with the postoperative spherical equivalent values than those taken with the micrometer. CONCLUSIONS: The thickness measurement of corneal resections by both micrometry and pachometry is greatly influenced by tissue hydration status. When hydration is similar, the pachometer provides more accurate thickness readings than does the micrometer, as determined by correlations with intended refractive results.

Identification of mothers at risk for congenital heart block and other neonatal lupus syndromes in their children. Comparison of enzyme-linked immunosorbent assay and immunoblot for measurement of anti-SS-A/Ro and anti-SS-B/La antibodies.

OBJECTIVE: To identify the fine specificity patterns of maternal anti-SS-A/Ro and anti-SS-B/La antibodies that are associated with the birth of a child with transient or permanent manifestations of neonatal lupus syndromes, and to suggest a predictor algorithm for use in counseling. METHODS: Sera were obtained from 4 groups of mothers: 57 whose children had congenital heart block, 12 whose children had transient dermatologic or hepatic manifestations of neonatal lupus but no detectable cardiac involvement, 152 with systemic lupus erythematosus and related autoimmune diseases, who gave birth to healthy infants, and 30 with autoimmune diseases whose pregnancy resulted in miscarriage, fetal death, or early postpartum death unrelated to neonatal lupus. Antibodies to SS-A/Ro and SS-B/La were assessed by enzyme-linked immunosorbent assay (ELISA) and by sodium dodecyl sulfate (SDS)-immunoblot. RESULTS: Anti-SS-A/Ro antibodies were identified by ELISA in 100%, 91%, 47%, and 43% of the mothers of infants with heart block, with transient neonatal lupus, healthy infants, and fetal death, respectively. High titers of anti-SS-A/Ro antibodies were present more often in mothers of children with cardiac disease or transient neonatal lupus than in either of the other 2 groups. Maternal antibodies to SS-B/La were detected by ELISA in 76% of the heart block group, 73% of the cutaneous neonatal lupus group, 15% of the group with healthy children, and 7% of the fetal death group. On SDS-immunoblot, sera from 91% of the heart block group mothers who had antibodies to SS-A/Ro but not to SS-B/La recognized at least 1 SS-A/Ro antigen, with significantly greater reactivity against the 52-kd component. In contrast, only 62% of the anti-SS-A/Ro positive, anti-SS-B/La negative responders in the healthy group recognized the 52-kd and/or the 60-kd component. Although there was no profile of anti-SS-A/Ro response unique to the mothers of children with heart block or cutaneous manifestations of neonatal lupus, only 1% of the healthy infants were born to mothers with antibodies directed to both the 52-kd SS-A/Ro and 48-kd SS-B/La antigens and not to the 60-kd SS-A/Ro antigen. CONCLUSION: Women with antibodies to both SS-A/Ro and SS-B/La have an increased risk of giving birth to children with neonatal lupus, especially if the anti-SS-A/Ro response identifies the 52-kd component on SDS-immunoblot. Women whose sera contain only anti-SS-A/Ro antibodies in low titer and only recognize determinants that are altered by conditions of SDS-immunoblot have a low risk for giving birth to a child with neonatal lupus. Specific antibody profiles do not distinguish among the manifestations of the neonatal lupus syndromes.

Two pathways of CD11b/CD18-mediated neutrophil aggregation with different involvement of protein kinase C-dependent phosphorylation.

The characteristics of homotypic neutrophil aggregation, mediated by the adhesion molecule CD11b/CD18, differ according to whether activation takes place via intracellular protein kinase C(PKC) inducers or chemoattractants. In response to diacylglycerol (DAG) analogues such as PMA and 1,2-dioctanoyl-sn-glycerol, a prolonged cellular aggregation occurs that is associated with intense phosphorylation of the CD18 beta-chain. In response to the chemoattractant FMLP, a more transient aggregation event results that is associated with minimal beta-chain phosphorylation. By using the PKC inhibitor staurosporine, we now show that these differences are likely to reflect two different pathways of activation. Both aggregation and phosphorylation induced by DAG analogues are completely abolished by staurosporine in a parallel dose-dependent manner. Conversely, FMLP-induced aggregation is enhanced and prolonged by staurosporine whereas the associated minimal phosphorylation event is further diminished by staurosporine. Accordingly, activation of neutrophil aggregation by DAG analogues is associated with and presumably due to phosphorylation of the CD18 beta-chain. This intense phosphorylation occurs via a staurosporine-sensitive kinase such as PKC. FMLP, on the other hand, appears to activate CD11b/CD18 by a distinct mechanism. This latter mechanism does not seem to be dependent on what may be a minor PKC-induced phosphorylation of the beta-chain, and indeed is enhanced by inhibition of PKC. Of note, staurosporine was also found to cause selective release of specific granules with concomitant increase in surface display of CD11b/CD18. These data further support previous observations that up-regulation of this adhesive molecule is not the primary event in the induction of cellular adhesiveness.

Effective separation of the 52 kDa SSA/Ro polypeptide from the 48 kDa SSB/La polypeptide by altering conditions of polyacrylamide gel electrophoresis.

A method is described for the separation of the 52 kDa SSA/Ro polypeptide from the 48 kDa SSB/La polypeptide. These two proteins anomalously co-migrate with the same relative mass under conditions of conventional sodium dodecyl sulfate polyacrylamide gel electrophoresis according to Laemmli using a stock solution of acrylamide: bisacrylamide 30:0.8, ratio = 37.5. A higher ratio of monomer to cross-linker, ratio = 172.4 used in a 15% acrylamide solution, readily separates the two peptide chains. This method facilitates the detection of the 52 kDa SSA/Ro component which otherwise might have been incorrectly assigned as a 48 kDa SSB/La polypeptide.