Epithelial and stromal changes induced by intacs examined by three-dimensional very high-frequency digital ultrasound.

PURPOSE: To examine epithelial and stromal layers by three-dimensional very high-frequency (VHF) digital ultrasound scanning before and after implantation of Intacs (intracorneal ring segments [ICRS]). METHODS: Three-dimensional scanning was performed in five eyes before and 3 months after Intacs insertion. Digital signal processing techniques provided high-resolution B-scan imaging and I-scan traces for high-precision (1-microm) three-dimensional pachymetry. Thickness maps of individual corneal layers were constructed of the epithelium, stroma, and full cornea before and after surgery. Difference maps for epithelium and stroma were produced to examine anatomical changes in the thickness profile induced in each layer and correlate these to refractive changes. RESULTS: B-scan examination revealed stromal and epithelial anatomy anterior and adjacent to the Intac. Ring depth could be measured topographically. There was stromal lamellar displacement by the ring segments that produced a concave anterior stromal groove within an annulus central to the ring. Epithelial filling of this concavity was shown in three dimensions in such a way as to produce orthogonally asymmetrical flattening of the corneal surface, thus potentially accounting for induced astigmatism. Mapping of the central stroma demonstrated thickening, potentially also accounting for astigmatic changes ascribable to orthogonal asymmetry. CONCLUSIONS: VHF digital ultrasound scanning provided imaging and three-dimensional thickness mapping of corneal layers, enabling anatomical evaluation of the changes induced in the cornea by Intacs.

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.

Avoiding serious corneal complications of laser assisted in situ keratomileusis and photorefractive keratectomy.

OBJECTIVE: To identify avoidable factors that can lead to serious complications of laser refractive surgery (photorefractive keratectomy [PRK] and laser assisted in situ keratomileusis [LASIK]). DESIGN: Noncomparative case series. PARTICIPANTS: Twenty-seven eyes of 19 patients who had undergone either LASIK or PRK with severe complications accrued retrospectively. INTERVENTION: Review of clinical records. MAIN OUTCOME MEASURES: Symptoms, refractive outcome, and assessment of avoidable factors contributing to the complication. RESULTS: Patients were analyzed in four groups: group 1, scarring with ectasia; group 2, unrecognized keratoconus; group 3, flap related LASIK complications; and group 4, multiple retreatments. The 8 eyes with scarring and ectasia presented with the worst vision, 20/400 uncorrected visual acuity and 20/200 best spectacle-corrected visual acuity, with avoidable factors considered as high or difficult prescriptions with multiple retreatments. Four eyes in two patients with possible forme fruste keratoconus showed worsening irregular astigmatism. Laser assisted in situ keratomileusis flap complications included six eyes with partial laser treatment under an incomplete flap with subsequent severe irregular astigmatism. Six eyes in three patients who had undergone an average of three multiple retreatments showed decreased vision with irregular astigmatism. CONCLUSIONS: Certain severe complications of laser refractive surgery likely can be avoided by using caution when treating high prescriptions, particularly with retreatments, recognizing early keratoconus and avoiding laser treatment under a partial flap in LASIK.

Accuracy of Orbscan total optical power maps in detecting refractive change after myopic laser in situ keratomileusis.

PURPOSE: To determine whether the refractive change obtained using the Orbscan-derived total optical power (TOP) map is in concordance with the manifest refractive change produced by laser in situ keratomileusis (LASIK). SETTING: LASIK Vision Canada, Vancouver, BC, Canada (an ambulatory surgical center for refractive surgery). METHODS: Twenty eyes of 10 consecutive bilateral LASIK patients were included in the study. Orbscan topographical analysis and manifest refraction were performed preoperatively and at least 1 month postoperatively. The change in manifest refraction (corrected to the corneal plane) before and after LASIK was correlated with the corneal power change averaged within the 2.0, 3.0, 4.0, and 5.0 mm diameter zones of TOP and axial power maps. RESULTS: The central 4.0 mm zone TOP map gave the best correlation between manifest refractive change and Orbscan-measured corneal power change (r2 = 0.835, P < .004). The correlation was higher with TOP maps than with anterior axial power maps. CONCLUSION: The corneal power change measured by the Orbscan TOP maps correlated highly with the changes in manifest refraction after LASIK.

Corneal endothelial deposits in patients with HIV infection or AIDS: epidemiologic evidence of the contribution of rifabutin.

BACKGROUND: We noted a number of patients with unusual fine, stellate corneal endothelial deposits. The distribution of the deposits appeared to be concentric, involving mostly the periphery. We postulated that the changes might be related to the use of rifabutin rather than to cytomegalovirus (CMV) retinitis. We conducted a study among patients infected with HIV to assess the factors associated with these corneal changes. METHODS: All patients with HIV infection or AIDS who presented to an ocular AIDS clinic in Vancouver between May 16 and July 4, 1996, were examined for the presence of corneal endothelial deposits. The clinical history was noted in a masked fashion. RESULTS: Of the 162 patients examined, 25 showed fine, diffuse, white, stellate corneal endothelial deposits occurring predominantly in the periphery. The presence of the deposits was associated with rifabutin use (odds ratio 5.6, 95% confidence interval 2.5 to 12.9) independent of the presence of CMV retinitis, the CD4 count, the presence of uveitis and use of other medications. INTERPRETATION: Corneal endothelial deposits found in patients with HIV infection are associated with rifabutin use independent of the presence of CMV retinitis. The deposits should be monitored to determine their clinical significance.

An epidemiologic investigation of unexpected refractive errors following cataract surgery.

OBJECTIVE: To determine the extent and magnitude of unexpected refractive errors following cataract surgery with intraocular lens (IOL) implantation and to determine what characteristics were associated with the errors. DESIGN: In this nonconcurrent prospective study, preoperative, intraoperative and postoperative information was collected from the charts of the 523 consecutive patients who underwent cataract extraction and polymethylmethacrylate IOL implantation performed by one of nine participating surgeons between Jan. 1 and Apr. 30, 1995, or the same dates in 1996. SETTING: University-affiliated eye care centre in Vancouver. OUTCOME MEASURE: Postoperative excess correction, calculated for each patient by subtracting the actual postoperative spherical equivalent from the expected spherical equivalent. Eyes with an excess correction of more than 1.00 dioptre were considered "overcorrected." RESULTS: Univariate analysis showed that the formula used to calculate the lens power, axial length, year of surgery, A-constant/surgeon factor used and lens manufacturer were associated with overcorrection. In a logistic regression model, lens manufacturer was the only variable independently associated with overcorrection. CONCLUSIONS: Routine reporting and follow-up is necessary to identify this kind of "outbreak" and the associated factors. The current guidelines of the Health Protection Branch, Health Canada, for evaluation of IOLs that have changed manufacturers are not adequate to identify the kind of error that we detected.

Visual function among corneal disease patients waiting for penetrating keratoplasty in British Columbia.

PURPOSE: We sought to test the applicability of a well-documented visual function assessment (VF-14) in corneal disease patients wait-listed for penetrating keratoplasty to determine if it would be a valuable addition to a priority scheme. METHODS: A systematic random sample of patients wait-listed for penetrating keratoplasty in British Columbia was selected and administered the VF-14. RESULTS: The mean VF-14 score was 67.2; it was correlated with best corrected vision. Immigrants had lower VF-14 scores and they considered fewer of the questions applicable to them. There was a correlation between the number of questions considered applicable and the VF-14 score. CONCLUSIONS: As currently constituted the VF-14 is probably not a useful tool in a multi-cultural population in North America. We propose revisions to the visual function assessment and suggest its inclusion in a priority scheme for penetrating keratoplasty that also includes pain and other clinical indices.

Creation of priority criteria for corneal transplantation and analysis of factors associated with surgery following implementation.

PURPOSE: We sought to test the effectiveness and application of a system for prioritizing corneal disease patients for corneal transplantation. METHODS: All patients wait-listed for corneal transplantation in British Columbia in April 1995 were followed for 10 months to determine whether they received surgery and to assess the application of recently introduced priority criteria. RESULTS: The factors that determined whether a patient had surgery were as follows: having vision in one eye only, being female, having progressive disease, and experiencing pain. The surgeon involved was also a factor. Overall, the priority system did not adequately predict who had surgery and who did not have surgery. CONCLUSIONS: The priority system needs to be re-structured to reduce the contribution of months waited and to more adequately take into account patient need. Furthermore, its application by individual surgeons needs to be strengthened.

Corneal decompensation after cataract surgery. An outbreak investigation in Asia.

PURPOSE: During 5 days in January 1994, two visiting expatriate ophthalmologists performed extracapsular cataract surgery on 111 patients at a nonprofit hospital in Asia. The authors investigated the development of postoperative corneal edema. METHODS: An epidemiologic and clinical investigation was undertaken by a review of clinical charts, interview of personnel involved, an examination and interview of patients who underwent surgery, and a laboratory simulation of the disinfection procedure used. RESULTS: Follow-up was available on 58% of the patients. The attack rate was at least 37% and likely to be approximately 64%. The attack rate was highest the first 2 days of surgery. Multivariate analysis showed that the day of surgery was the only characteristic significantly associated with the presence of corneal edema. A simulation of the disinfection technique used (soaked in 2% glutaraldehyde and rinsing) showed that significant levels of glutaraldehyde remain in instruments with small lumens after the rinse. CONCLUSION: The epidemiologic data and simulation information are compatible; the lack of adequate rinsing of small lumen instruments soaked in glutaraldehyde is the most probable cause of this incident. Recommendations for surgeons on surgical expeditions are proposed.

Morphologic and functional alterations of mucosal T cells by cholera toxin and its B subunit.

Despite the mucosal immunogenicity and adjuvanticity in vivo of cholera toxin (CT), both CT and CT B subunit are strong inhibitors of T cell activation in vitro. This study asked whether such T cell inhibition is relevant to the mucosal effects of CT in vivo. The activation of T cells pulsed in vitro for only 15 to 120 min with CT or CT B subunit, respectively, was inhibited, consistent with the expected short exposure times in vivo. Although both CD8+ and CD4+ T cells were inhibited in vitro, CD8+ T cells bound more toxin and were inhibited to a greater degree than were CD4+ T cells. Intestinal gavage of mice with 10 micrograms CT did not alter the overall composition of Peyer's Patch, mesenteric lymph node, or spleen but did cause a marked depletion of intraepithelial lymphocytes, mainly CD8+ T cells, and of lymphocytes in the dome epithelium over Peyer's Patch. To determine whether such inhibition of T cells was functionally relevant in vivo, T cells from mice fed keyhole limpet hemocyanin (KLH) were adoptively transferred into naive recipients, who were then parenterally immunized. T cells from mice fed KLH alone inhibited both the systemic IgG and secretory IgA anti-KLH response, but T cells from mice fed KLH plus CT did not, indicating that mucosally applied CT was able to abrogate the induction of this suppressor T cell. We conclude that one of the mechanisms of CT's mucosal effects in vivo is the inhibition of certain mucosal T cell functions and alteration of the regulatory T cell environment in gut-associated lymphoid tissue.

The progressive outer retinal necrosis syndrome. A variant of necrotizing herpetic retinopathy in patients with AIDS.

BACKGROUND: The progressive outer retinal necrosis syndrome is a recently recognized variant of necrotizing herpetic retinopathy. This report characterizes more fully its clinical features and course. METHODS: Using standardized clinical criteria, patients with progressive outer retinal necrosis syndrome from four institutions were identified. Patient records were reviewed retrospectively for the following data: medical and demographic characteristics, presenting symptoms, physical findings, course, responses to treatment, and outcomes. RESULTS: Thirty-eight patients (65 involved eyes) were studied. All had acquired immune deficiency syndrome. A known history of cutaneous zoster was documented in 22 (67%) of 33 patients. Median CD4 lymphocyte count was 21/mm3 (range, 0-130/mm3). Median follow-up was 12 weeks. The most common presenting symptom was unilateral decreased vision (35 of 65 eyes, 54%); median visual acuity at presentation was 20/30 (range, 20/20 to no light perception [NLP]). Anterior chamber and vitreous inflammatory reactions were absent or minimal in all patients. Typical retinal lesions were multifocal, deep opacities scattered throughout the periphery, although macular lesions also were present in 21 eyes (32%) at diagnosis. Lesions progressed rapidly to confluence. Initial intravenous antiviral therapy appeared to reduce disease activity in 17 (53%) of 32 eyes, but treatment did not alter final visual outcome. Visual acuity was NLP in 42 (67%) of 63 eyes within 4 weeks after diagnosis. Retinal detachment occurred in 43 (70%) of 61 eyes, including 13 (93%) of 14 eyes that received prophylactic laser retinopexy. CONCLUSION: The progressive outer retinal necrosis syndrome is characterized by features that distinguish it from cytomegalovirus retinopathy, acute retinal necrosis syndrome, and other necrotizing herpetic retinopathies. Visual prognosis is poor with current therapies.

In vitro and in vivo 2',5'-oligoadenylate synthetase activity induced by recombinant DNA-derived bovine interferon alpha I1 in bovine alveolar macrophages and blood mononuclear cells.

Biological responses to recombinant DNA-derived bovine interferon alpha (rBoIFN-alpha I1) by bovine alveolar macrophages were examined by measuring viral yield reduction and 2',5'-oligoadenylate synthetase (2',5'-OAS) production by IFN-treated cells. In vitro IFN pretreatment of alveolar macrophages reduced viral yield in cultures challenged exposed with parainfluenza-3 virus, compared with control cultures. In vitro treatment of alveolar macrophages with IFN also resulted in increased 2',5'-OAS activity. The 2',5'-OAS activity was measured in alveolar macrophages and blood mononuclear leukocytes of calves injected IM with 3.6 x 10(6) U of rBoIFN-alpha I1/kg of body weight. The IFN action was monitored by measuring 2',5'-OAS activity of blood mononuclear leukocytes beginning 6 days before and ending 24 hours after IFN treatment. The 2',5'-OAS activity in the blood mononuclear leukocytes sharply increased 24 hours after IFN treatment, indicating response to IFN. The alveolar macrophages collected from the same calves 24 hours after IFN administration also had increased 2',5'-OAS activity, compared with alveolar macrophages from the same calves collected 6 days before treatment. Increased 2',5'-OAS activity indicates: a possible mechanism of IFN action in cattle that may be responsible for viral yield reduction; potential use of high enzyme activity as a marker for IFN induction; and potential use of 2',5'-OAS activity as a marker for determining effects of IFN on bovine macrophages and other cells of the bovine immune system.

Biofilm and scleral buckle-associated infections. A mechanism for persistence.

Scleral buckle infections tend to be persistent as well as resistant to antimicrobial treatment. Often, scleral buckle infections require removal of the buckling elements for resolution. To determine if bacteria are able to persist on scleral buckles by elaborating a glycocalyx matrix or biofilm that offers protection against host defenses and antimicrobial treatment, the authors cultured 28 scleral buckle elements removed for infection and extrusion. Bacteria were isolated from 18 elements (64%). The most frequently isolated bacteria were Staphylococcus epidermidis and other coagulase-negative staphylococci (8), Staphylococcus aureus (3), corynebacteria (3), Mycobacterium chelonei (3), and Proteus mirabilis (3). Eleven (65%) of 17 buckles evaluated with scanning electron microscopy demonstrated the presence of bacteria encased in biofilm. Biofilm was demonstrated on the surfaces and ends of solid silicon elements. In the silicon sponges, biofilm also extended into the matrix of the sponges. The authors believe that bacterial production of biofilm offers an explanation for the persistence of scleral buckle infections and their ability to withstand antimicrobial treatment.

The challenge of eye disease: the patient's perspective.

An educational symposium was organized to allow patients to be instructors by encouraging them to discuss their conditions, how they perceived their eye problems and the care they received, and the effect of their experience on their lives. Patients repeatedly stressed the need they felt for more time to discuss their disorders and more communication at all levels. An increasing use of patient information material, using printed materials and video, may partially alleviate the problem of a lack of communication.

Neisseria gonorrhoeae keratoconjunctivitis.

Clinical and laboratory findings of 47 patients with ocular infections secondary to Neisseria gonorrhoeae during a 5 1/2-year period were reviewed. In 16 patients (34%), corneal involvement was noted. Six of these patients had a severe ulcerative keratitis resulting in permanent visual loss and five required surgery for a corneal perforation. Patients with corneal involvement were older and presented later in the course of their disease than patients with isolated conjunctival involvement (P less than 0.005). An out-patient regimen of intramuscular antibiotics (either penicillin, cephalosporin, or spectinomycin [Trobicin]) appeared to be effective for infections limited to the conjunctiva in adults. If a topical antibiotic ointment is used in addition to parenteral antimicrobial agents, the authors' laboratory sensitivities suggest that erythromycin may be the drug of choice.

Branhamella catarrhalis keratitis.

Branhamella catarrhalis, formerly known as Neisseria catarrhalis, has structural similarities to Neisseria gonorrhoeae, but is generally considered to be nonpathogenic. We studied the clinical and laboratory data of four previously reported cases and six additional cases of B. catarrhalis keratitis. All patients had a predisposing ocular or systemic condition, or both. There were various clinical characteristics, but in most cases the infiltrate occurred in the central or paracentral cornea. A prompt response to treatment with a cephalosporin and aminoglycoside antibiotic was noted in all cases. Two patients had corneal perforations, which probably resulted from a delay in treatment. Gram-negative diplococci from corneal scrapings may not necessarily represent N. gonorrhoeae.