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Background: Approximately 50% of newly diagnosed glioblastomas (GBMs) harbor epidermal growth factor receptor gene amplification (EGFR-amp). Preclinical and early-phase clinical data suggested efficacy of depatuxizumab mafodotin (depatux-m), an antibody-drug conjugate comprised of a monoclonal antibody that binds activated EGFR (overexpressed wild-type and EGFRvIII-mutant) linked to a microtubule-inhibitor toxin in EGFR-amp GBMs., Methods: In this phase III trial, adults with centrally confirmed, EGFR-amp newly diagnosed GBM were randomized 1:1 to radiotherapy, temozolomide, and depatux-m/placebo. Corneal epitheliopathy was treated with a combination of protocol-specified prophylactic and supportive measures. There was 85% power to detect a hazard ratio (HR) ≤0.75 for overall survival (OS) at a 2.5% 1-sided significance level (ie traditional two-sided p ≤ 0.05) by log-rank testing., Results: There were 639 randomized patients (median age 60, range 22-84; 62% men). Prespecified interim analysis found no improvement in OS for depatux-m over placebo (median 18.9 vs. 18.7 months, HR 1.02, 95% CI 0.82-1.26, 1-sided p = 0.63). Progression-free survival was longer for depatux-m than placebo (median 8.0 vs. 6.3 months; HR 0.84, 95% confidence interval [CI] 0.70-1.01, p = 0.029), particularly among those with EGFRvIII-mutant (median 8.3 vs. 5.9 months, HR 0.72, 95% CI 0.56-0.93, 1-sided p = 0.002) or MGMT unmethylated (HR 0.77, 95% CI 0.61-0.97; 1-sided p = 0.012) tumors but without an OS improvement. Corneal epitheliopathy occurred in 94% of depatux-m-treated patients (61% grade 3-4), causing 12% to discontinue., Conclusions: Interim analysis demonstrated no OS benefit for depatux-m in treating EGFR-amp newly diagnosed GBM. No new important safety risks were identified., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)

Purpose: To identify donor and recipient factors, including eye bank tissue observations, predictive of operative complications in the Cornea Preservation Time Study., Methods: One thousand three hundred thirty study eyes undergoing Descemet stripping automated endothelial keratoplasty for Fuchs dystrophy or pseudophakic/aphakic corneal edema were randomized to receive a donor cornea with preservation time (PT) of 0 to 7 days (N = 675) or 8 to 14 days (N = 655). Donor factors included demographics, prelamellar corneal and postlamellar lenticule dissection thickness, central endothelial cell density, and tissue processing time. Recipient factors included demographics, intraocular pressure, and glaucoma medications or surgery (trabeculectomy, laser trabeculoplasty). Eye bank observations included donor tissue folds, pleomorphism/polymegethism, and endothelial cell abnormalities. Possible tissue-related operative complications were recorded including difficult donor lenticule unfolding and positioning. Multivariable logistic regression with backward selection was used to identify statistically significant (P < 0.01) associations between factors and operative complications., Results: The only factor predictive of operative complications [58 (4.4%) of 1330 surgeries] was prelamellar dissection donor corneal thickness (P = 0.002). For every 50 μm of donor corneal thickness prior to lamellar dissection, operative complication odds increased by 40% (odds ratio [99% confidence interval (CI)]: 1.40 [1.06-1.83]) adjusting for PT and whether the epithelium was on or off. The estimated mean prelamellar dissection donor corneal thickness for PT 0 to 7 days was 537 μm (99% CI: 516 μm-558 μm) compared with 567 μm (99% CI: 546 μm-588 μm) for PT 8 to 14 days (P < 0.001)., Conclusions: Thicker donor tissue (prelamellar dissection) is associated with operative complications and should be considered in tissue selection for Descemet stripping automated endothelial keratoplasty lenticule preparation.

Purpose: Fuchs corneal dystrophy (FD) is a common cause of endothelial keratoplasty. Recently, a series of FD cases treated with Descemet stripping only (DSO) demonstrated recovery of the central endothelium without transplantation of donor cells. Ripasudil, a rho kinase inhibitor, has been shown to promote corneal endothelial wound healing in animal models. This study prospectively evaluated the use of ripasudil in patients undergoing DSO for FD., Methods: Enrolled patients underwent DSO with or without cataract surgery, performed by 1 surgeon. On the first postoperative day, patients were assigned to topical ripasudil 0.4% (Glanatec) 4 times a day for 2 months or no ripasudil and followed up monthly for the first 6 months and then at 9 and 12 months after surgery. Endothelial cell density (ECD) and pachymetry were evaluated at each postoperative visit., Results: Eighteen patients were enrolled, including 8 women and 1 man in each group. Overall, patients who underwent DSO with ripasudil recovered vision more quickly (4.6 vs. 6.5 weeks, P < 0.01). In addition, the ripasudil group had a statistically significantly higher average ECD at 3, 6, and 12 months. The patients in the DSO observation group had a 10% decrease in peripheral ECD when comparing counts before surgery with counts 12 months after surgery (P < 0.05). In the DSO ripasudil group, there was no significant difference between peripheral ECD at preoperative baseline versus 12 months after surgery., Conclusions: DSO with topical rho kinase inhibitors may be an alternative treatment for patients with FD and a peripheral ECD greater than 1000 cells/mm.

Purpose: To identify factors related to graft rejection following Descemet stripping automated endothelial keratoplasty (DSAEK) in the Cornea Preservation Time Study (CPTS)., Design: Cohort study within a multicenter randomized clinical trial., Methods: A total of 1330 eyes of 1090 subjects undergoing DSAEK were randomized to receive a donor cornea with preservation time (PT) of 0-7 days (n = 675) or 8-14 days (n = 655) and followed for 3 years. Central endothelial cell density (ECD) was determined by a central image analysis reading center. Multivariable Cox models adjusted for PT, recipient diagnosis, and surgeon effect were used to identify factors associated with rejection., Results: Cumulative probability of definite graft rejection was 3.6% (99% confidence interval 2.5%-5.3%). Younger recipient age was associated with graft rejection (P < .001; hazard ratio: 0.53 [0.33, 0.83] per decade). PT, donor-recipient sex mismatch, recipient diagnosis, recipient race, graft size, discontinuation of topical corticosteroids and immune-modulators, prior immunizations within 3 months, and prior glaucoma surgery were not associated with rejection (P > .01). Among clear grafts with an ECD measurement at baseline and 3 years (n = 913), endothelial cell loss (ECL) was greater in eyes that experienced a rejection episode (n = 27) than in those that did not (n = 886) (48% vs 38%, P = .03). Twelve of 44 eyes (27%) with definite graft rejection subsequently failed, comprising 15% of the 79 failures in the CPTS., Conclusions: Graft rejection is uncommon after DSAEK and more likely with younger age, in a study cohort mostly > 50 years old. Rejection increases ECL, but it is not a leading cause of DSAEK failure., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: To associate donor, recipient, and operative factors with graft success 3 years after Descemet stripping automated endothelial keratoplasty (DSAEK) in the Cornea Preservation Time Study (CPTS)., Design: Cohort study within a multicenter, double-masked, randomized clinical trial., Participants: One thousand ninety individuals (1330 study eyes) with a median age of 70 years undergoing DSAEK for Fuchs endothelial corneal dystrophy (94% of eyes) or pseudophakic or aphakic corneal edema (PACE; 6% of eyes)., Methods: Eyes undergoing DSAEK were randomized to receive a donor cornea with preservation time (PT) of 0 to 7 days (n = 675) or 8 to 14 days (n = 655). Donor, recipient, and operative parameters were recorded prospectively. Graft failure was defined as regraft for any reason, a graft that failed to clear by 8 weeks after surgery, or an initially clear graft that became and remained cloudy for 90 days. Failure in the first 8 weeks was classified further as primary donor failure or early failure, in the absence or presence of operative complications, respectively. Proportional hazards and logistic regression models were used to estimate risk ratios (RR) and 99% confidence intervals (CIs) for graft failure., Main Outcome Measures: Graft success at 3 years., Results: One thousand two hundred fifty-one of 1330 grafts (94%) remained clear at 3 years and were considered successful. After adjusting for PT, tissue from donors with diabetes (RR, 2.35; 99% CI, 1.03-5.33) and operative complications (RR, 4.21; 99% CI, 1.42-12.47) were associated with increased risk for primary or early failure. Preoperative diagnosis of PACE (RR, 3.59; 99% CI, 1.05-12.24) was associated with increased risk for late failure by 3 years after surgery compared with Fuchs dystrophy. Graft success showed little variation among other factors evaluated, including donor age (RR, 1.19 per decade; 99% CI, 0.91-1.56 per decade), preoperative donor endothelial cell density (RR, 1.10 per 500 cells; 99% CI, 0.74-1.63 per 500 cells), graft diameter (RR, 1.22 per 1 mm; 99% CI, 0.39-3.76 per 1 mm), and injector use for graft insertion (RR, 0.92; 99% CI, 0.40-2.10)., Conclusions: Descemet stripping automated endothelial keratoplasty success in the early and entire postoperative period is more likely when the donor did not have diabetes and was without operative complications and in the long-term postoperative period in recipients with Fuchs dystrophy compared with those with PACE. Mechanisms whereby diabetic donors and PACE recipients reduce the rate of graft success after DSAEK warrant further study., (Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess donor rim culture results and outcomes of ocular infections in the Cornea Preservation Time Study (CPTS)., Methods: Donor corneal rim cultures were optional. Donor characteristics were assessed for association with positive cultures using the Fisher exact test and Poisson regression analyses. Incidence rates of ocular infections were estimated, and 95% confidence intervals were calculated., Results: Cultures were performed in 784 (58.9%) of the 1330 cases. For the 0 to 7-day versus 8 to 14-day preservation time groups, respectively, positive fungal growth occurred in 10 of 397 (2.5%) versus 5 of 387 (1.3%) corneas (P = 0.30), whereas positive bacterial cultures occurred in 6 of 397 (1.5%) versus 4 of 387 (1.0%) corneas (P = 0.75). Surgeon-prepared tissue remained a significant risk for positive fungal cultures [relative risk (RR) of surgeon- versus eye-bank-prepared, 2.85; 95% CI (1.02-7.98)], whereas younger donors [RR per year of age, 0.96; 95% CI (0.93-1.00)] and accidental death donors [RR of accident versus disease, 3.71; 95% CI (1.36-10.13)] were at a greater risk for positive bacterial cultures. Fungal infection (Candida glabrata) developed in 1 (6.7%) of 15 recipients with a positive fungal culture, and no recipient infections occurred with positive bacterial culture. With one additional fungal keratitis (Candida albicans) and one bacterial endophthalmitis (E. coli) with no rim culture performed, a total of 2 of 1330 eyes (0.15%) developed fungal and 1/1330 eyes (0.08%) developed bacterial postkeratoplasty infections., Conclusions: A longer preservation time was not associated with a higher rate of positive donor rim cultures. The overall rate of infection across the entire cohort was low.

Purpose: To study the adherence of rheumatologists to the hydroxychloroquine (HCQ) dosing guidelines established by the American Academy of Ophthalmology in 2011 and 2016., Design: Retrospective review of electronic medical records (EMRs) in an integrated health care system., Participants: All rheumatology patients started on HCQ who were seen by a NorthShore ophthalmologist between the years 2009 and 2016., Methods: Data on patient weights, height, gender, and HCQ dosage were extracted from the EMR. The recommended maximum starting dose was determined using 2 formulas based on ideal or actual body weight., Main Outcome Measures: The percentage of patients whose dose exceeded the recommended maximum., Results: A total of 554 patients on HCQ were identified. Some 50% of the patients had been placed on excess initial doses according to the 2011 guidelines, and 47% of the patients had been placed on excess initial doses according to the 2016 guidelines. The introduction of the guidelines had no appreciable effect on HCQ dosing. A separate analysis of all patients currently receiving maintenance HCQ therapy demonstrated excess dosing in 297 of 527 (56%), according to the 2016 guidelines., Conclusions: Approximately one half of all patients started on HCQ by NorthShore rheumatologists received doses in excess of the recommended maximum, and slightly more than one-half of all patients currently on treatment continue to receive excess doses. Our data suggest that the publication of the consensus guidelines in 2011 had no appreciable effect on HCQ dosing and that transitioning to the 2016 dosing modification is unlikely to change this outcome unless additional steps are taken to improve adherence., (Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the incidence of adverse reactions after corneal transplantation, reported to the Eye Bank Association of America., Methods: Incidence of adverse reactions from January 1, 2007, to December 31, 2014, was analyzed., Results: Of the 354,930 transplants performed in the United States, adverse reactions were reported in 494 cases (0.139%). Primary graft failure (PGF) predominated (n = 319; 0.09%) followed by endophthalmitis (n = 99; 0.028%) and keratitis (n = 66; 0.019%). The procedure type predominantly associated with PGF was endothelial keratoplasty (EK) in 56% (n = 180; 11 per 10,000 grafts), followed by penetrating keratoplasty (PK) in 42% (n = 135; 6.9 per 10,000 grafts). The procedure type predominantly associated with endophthalmitis and keratitis was EK in 63% (n = 104; 6.3 per 10,000 grafts) followed by PK in 34% (n = 56; 2.8 per 10,000 grafts), anterior lamellar keratoplasty in 1% (n = 2; 2.7 per 10,000 grafts), and keratoprosthesis in 1% (n = 2; 12.4 per 10,000 grafts). Although the incidence of PGF and endophthalmitis between PK and EK was noteworthy, the difference was not statistically significant (P = 0.098). Endophthalmitis-associated pathogens were isolated in 78% of cases: predominantly Candida species (65%), gram-positive organisms (33%), and gram-negative rods (2%). Keratitis-associated pathogens were isolated in 64% of cases: predominantly Candida species (81%), Herpes simplex virus (7%), gram-negative organisms (7%), and gram-positive organisms (5%)., Conclusions: PGF was the most commonly reported adverse reaction, disproportionately associated with EK. An increasingtrend in the rate of endophthalmitis and keratitis was observed, disproportionately associated with EK and Candida species.

Purpose: Evidence of the transmission of disease via donor ocular tissue has been demonstrated for adenocarcinoma, rabies, hepatitis B virus, cytomegalovirus, herpes simplex virus, Creutzfeldt-Jakob disease, and a variety of bacterial and fungal infections., Methods: Although there is no evidence to date of disease transmission for HIV infection, syphilis, hepatitis C, hepatitis A, tuberculosis, HTLV-1 and -2 infection, active leprosy, active typhoid, smallpox, and active malaria, these entities remain contraindications for transplantation for all eye banks nationally and internationally. The potential sources of contamination include infected donors, during the process of removing tissue from cadaveric donors, the processing environment, and contaminated supplies and reagents used during processing. The transmissions of Herpes simplex virus and HSV via corneal graft have been shown to be responsible for primary graft failure. HSV-1 may also be an important cause of PFG., Results: The long latency period of some diseases, the emergence of new infectious disease, and the reemergence of others emphasize the need for long-term record maintenance and effective tracing capabilities., Conclusions: The standardization of definitions for adverse events and reactions will be necessary to support the prevention and transmission of disease. International classification of a unique identification system for donors will be increasingly important for vigilance and traceability in cross-national exportation of human cells, tissues, and cellular- and tissue-based products. Opportunities for continuous improvement exist as does the need for constant vigilance and surveillance.

Purpose: To evaluate presumed iatrogenic graft failure (PIGF) in Descemet stripping automated endothelial keratoplasty (DSAEK)., Methods: Deidentified data were collected retrospectively from the Illinois Eye Bank between April 2007 and May 2010. PIGF was defined as cases in which a repeat corneal transplant was performed <8 weeks after an initial DSAEK. Data collected for each case included days between initial DSAEK and regraft, regraft type (DSAEK vs. penetrating keratoplasty), precut versus surgeon-cut tissue, and number of DSAEKs distributed to individual surgeons. Ninety-three cases of PIGF were identified for a group of 46 surgeons who received 2504 corneas. Nine PIGF cases from 4 surgeons in cornea fellowships were analyzed separately. Individual surgeon failure rate and overall failure rate were calculated. Analysis of the overall failure rate was conducted without cases performed by surgeons who train fellows. Effect of surgical experience on PIGF was analyzed., Results: Overall presumed iatrogenic DSAEK failure rate was 3.66% (84 PIGF cases divided by 2294 corneas). Within the group of 4 surgeons that trained fellows, the failure rate was 4.29% (9 cases PIGF divided by 210 corneas). Average time to regraft was 27.5 ± 17.4 days. Initial diagnoses included Fuchs dystrophy, pseudophakic bullous keratopathy, edema, and other disease states. Average donor and recipient ages were 54.3 ± 13.0 and 71.7 ± 11.3 years, respectively. Use of precut versus surgeon-cut tissue did not affect overall failure rates. Failure rates of less experienced surgeons (21.8% ± 10.8%) were higher than more experienced surgeons (1.5% ± 1.4%)., Conclusions: Overall, DSAEK failure rates improve as surgeons gain experience. Failure rates in cornea fellowship programs are not excessive.

Background: Optical coherence tomography (OCT) provides microscopic retinal images. Optical coherence tomography is noninvasive, using light waves to produce detailed retinal images. Here, we investigate the ability of OCT to detect early choroidal neovascularization in age-related macular degeneration., Methods: Seventy-nine patients, diagnosed with nonexudative macular degeneration in one eye and exudative macular degeneration in the other were enrolled in this prospective, observational, nonrandomized study. Participants underwent examination (visual acuity, intraocular pressure, biomicroscopy, and ophthalmoscopy) followed by OCT in the study eye (nonexudative macular degeneration eye) every 3 months for 2 years. If examination did not show choroidal neovascularization, but OCT images raised suspicion, patients were reexamined in 4 weeks to 6 weeks and/or fluorescein angiography was performed. Visual acuity, OCT anomaly detected, and time between OCT and fluorescein angiography detection were examined., Results: Fifteen (19%) patients developed exudative macular degeneration, as confirmed by fluorescein angiography, in the study eye. Four additional patients showed potential exudative macular degeneration on OCT only. Of the 15 patients who developed exudative macular degeneration, 13 had disease progression identified on OCT before examination and/or fluorescein angiography showed changes. Subretinal pigment epithelium fluid was the most common OCT anomaly, with development of sub-/intraretinal fluid also visible., Conclusion: Optical coherence tomography could be a powerful screening tool for patients with age-related macular degeneration at high risk for developing choroidal neovascularization.

Purpose: The etiology of keratoconus has been the subject of numerous studies. Here, we review the body of literature that attempts to determine what causes keratoconus., Methods: A review of the published literature was performed to evaluate the possible causes of keratoconus and how the different etiologies may play a role in the development of this disease., Results: Peer-reviewed published papers and recent abstracts concerning the different etiologies of keratoconus were reviewed and discussed. Biochemical, genetic, and environmental factors are reviewed. The role of eye rubbing and atopic disease are explored., Conclusions: We agree with the hypothesis that there is a genetic predisposition that requires a "second hit" or environmental event to elicit progressive disease in keratoconus. Eye rubbing may serve as the "second hit" in some predisposed individuals. Inflammatory mediator studies question if keratoconus is really a noninflammatory thinning disorder of the cornea.

Purpose: To assess surgeon satisfaction with precut corneal tissue from 1 eye bank for Descemet stripping automated endothelial keratoplasty (DSAEK). Surgical techniques and predictors of procedural success were also examined., Methods: A 19-question survey was completed by 53 surgeons around the United States for 197 DSAEK cases using prepared corneal allograft tissue from the Iowa Lions Eye Bank. Surgeries were performed between April 1 and December 31, 2006; surveys were completed retrospectively within a few weeks of surgery., Results: Tissue was found to be acceptable in 98% of DSAEK cases reported. Difficulties with precut tissue (eg, lack of anterior cap adherence to the posterior lamella, not visible or decentered central dot, anterior edge undermining) were reported in approximately 10% of cases. A rebubbling procedure was performed in 23% of cases for donor dislocations. The donor lenticule adhered, with resulting corneal deturgescence, in 86% of cases. Surgeons declared a successful procedure in 92% of cases. Of the 14 unsuccessful cases, donor tissue quality was the underlying etiology in only 1 case. Procedural success rates were related to surgeon experience (P = 0.002), lenticule adherence after only 1 anterior chamber air bubble (P = 0.005), no small perforations to release fluid (P = 0.005), and the presence of corneal deturgescence (P = 0.002)., Conclusions: The use of precut tissue for DSAEK is not associated with increased risk of complications related to tissue preparation. With standardization of precutting donor tissue, safety of DSAEK surgery may be improved while increasing surgeon efficiency.

Purpose of Review: Presbyopia-correcting intraocular lenses are widely available. Residual ametropia is one of the most common issues that can result in patient dissatisfaction. Options for correcting refractive surprises include piggyback intraocular lens implantation, corneal incisional surgery and laser correction. Excimer laser surgery is a safe and predictable method to correct residual amounts of ametropia in pseudophakic patients with monofocal intraocular lenses; however, there is scant published literature regarding this technique., Recent Findings: Presbyopia-correcting intraocular lenses require emmetropia for the best visual outcome, as small amounts of astigmatism or residual refractive errors can limit their visual performance. Laser-assisted in-situ keratomileusis and photorefractive keratectomy are safe and effective results in pseudophakic patients. Surgeons can refine the refractive outcome after intraocular lens implantation with the excimer laser to achieve better results and higher patient satisfaction., Summary: Excimer laser corneal surgery for fine-tuning residual ametropia after presbyopia-correcting intraocular lenses is a safe adjunct treatment to increase patient satisfaction. Which technique (photorefractive keratectomy or laser-assisted in-situ keratomileusis) to use depends on surgeon preference and patient characteristics, as both demonstrate similar results in published literature. Knowledge of all available refractive methods and technologies are crucial for improving outcomes in these patients.

Purpose: Blepharitis and meibomian gland dysfunction (MGD) are common sources of complaints from patients. To evaluate the effect on ocular symptoms, ocular findings, and serum and meibomian gland contents, patients with blepharitis and MGD were prospectively evaluated to determine the effects of dietary supplementation with omega-3 fatty acids., Methods: In a prospective randomized placebo-controlled masked trial, patients with simple obstructive MGD and blepharitis, who had discontinued all topical medications and tetracyclines, received oral omega-3 dietary supplementation consisting of two 1000-mg capsules 3 times a day. Patients were examined every 3 months for 1 year with the Ocular Surface Disease Index (OSDI) objective clinical measures, including tear production and stability, ocular surface and meibomian gland health, and biochemical plasma, red blood cell (RBC), and meibum evaluation. Primary outcome measures were change in tear breakup time (TBUT), meibum score, and overall OSDI score at 1 year., Results: At 1 year, the omega-3 group had a 36% and 31% reduction in their omega-6 to omega-3 fatty acid ratios in RBCs and plasma, respectively (P = .3), whereas the placebo group demonstrated no change. At 12 months, the omega-3 group had an improvement in TBUT, OSDI score, and meibum score. Changes in meibum content were observed in the omega-3 group (P = .21); the level of meibum saturated fatty acids decreased., Conclusions: This trial demonstrated a decrease in the RBC and plasma ratios of omega-6 to omega-3 in patients taking omega-3 dietary supplementation, as compared to controls, and improvements in their overall OSDI score, TBUT, and meibum score. This is the first demonstration of an induced change in the fatty acid saturation content in meibum as a result of dietary supplementation with omega-3 fatty acids.

Purpose: To describe a suture technique for Descemet stripping and endothelial keratoplasty (DSEK)., Methods: The technique was performed in 2 eyes of 2 patients with Fuchs endothelial corneal dystrophy. A double-armed 10-0 prolene suture on a CIF-4 needle was used to pull the donor corneal button into the recipient's anterior chamber without the use of forceps to hold the button. The suture was also used to unfold the lenticule in the eye without marking the stroma with gentian violet, to center the lenticule and to secure that in place., Results: No intraoperative problems occurred in either case. The suture technique was successfully used to pull the donor button into the host's eye and to unfold and center the button. Both lenticules were well centered and had minimal corneal edema. At 6 months, the central endothelial loss was 8% in the first case and 10% in the second., Conclusion: This suture technique for DSEK avoids the use of forceps and allows less traumatic donor button manipulation. It may be an effective alternative with low endothelial damage; further follow-up will determine the long-term effect on the central endothelial cell count.

Purpose: To describe a case of corneal ectasia with marked asymmetric progression attributable to encircling buckle surgery for retinal detachment., Methods: Case report., Results: A 72-year-old man developed clinical signs of pellucid marginal degeneration in 1 eye after placement of an encircling scleral buckle. The fellow eye showed normal slit-lamp examination, with topographic signs of forme-fruste pellucid marginal degeneration., Conclusion: Patients with forme-fruste pellucid marginal degeneration may show progression and clinical manifestations after encircling scleral buckle, probably by changes in ocular physiology and corneal biomechanics.

Purpose: To evaluate and compare the visual outcomes and accommodative amplitude in cataract patients after implantation of the Crystalens intraocular lens (IOL) (Eyeonics) versus standard monofocal IOLs., Setting: Ten clinics in a nationwide multicenter study in the United States., Methods: A multicenter comparative interventional case series with masked randomized postoperative examination of 224 eyes of 112 patients was performed by a single observer. Patients were divided into 2 groups (56 patients; 112 eyes each) depending on which IOL was implanted (Crystalens or monofocal). Accommodation was measured using 1 objective (dynamic retinoscopy) and 2 subjective methods (defocus and near point of accommodation). Visual acuity measurements were performed under the same conditions with standard visual acuity charts., Results: Uncorrected monocular near vision was significantly better in the Crystalens group than in the standard monofocal group, with 101 of 112 eyes (90%) and 17 of 112 (15%), respectfully, reading J3 or better postoperatively. All 56 Crystalens patients had a binocular uncorrected near visual acuity of J3 or better compared with 16 of 56 (29%) standard monofocal patients. The mean postoperative monocular (0.85 +/- 0.30 [SD] versus 0.70 +/- 0.19, P<.01) and binocular (1.16 +/- 0.17 versus 1.01 +/- 0.14, P<.01) distance uncorrected visual acuities were also better in the Crystalens group than in the control group. All patients in the study achieved a corrected distance visual acuity of 20/20 or better. Measures of accommodation were significantly higher in Crystalens patients than in the monofocal IOL patients (dynamic retinoscopy 2.42 +/- 0.39 diopters [D] versus 0.91 +/- 0.24 D, P<.01; monocular defocus 1.74 +/- 0.48 D versus 0.75 +/- 0.25 D, P<.01; monocular near point of accommodation 9.5 +/- 3.1 inches versus 34.7 +/- 9.8 inches, P<.01). Perceived accommodation (5.79 D) was significantly greater than the measured accommodation (1.96 to 2.42 D) in Crystalens patients (paired t test, P<.01)., Conclusions: The Crystalens IOL provided better uncorrected near and distance visual outcomes than standard monofocal IOLs in all analyses performed. Patients perceived a greater accommodation than measured. Understanding why this occurred could lead to valuable advances in accommodating IOL technology.

Objectives: To report the development of corneal ulcers in two children wearing Paragon Corneal Refractive Therapy (CRT) lenses., Methods: Two case reports of children who developed corneal ulcers when fit with Paragon CRT contact lenses, which were worn nightly, are discussed. Each patient presented with a bacterial corneal ulcer after wearing CRT contact lenses for less than 6 months. In the first patient, Pseudomonas aeruginosa was identified as the causative organism. In the second patient, Haemophilus influenza was cultured from the ulcer., Results: Both patients were treated with intensive, fortified antibiotics with rapid resolution of the corneal ulcers and preservation of vision. No surgical intervention was required., Conclusions: Paragon CRT lenses have been approved for use in patients of all ages. When used in children, these lenses may present unique problems. The absolute incidence of bacterial corneal ulcers in patients with CRT lenses are unknown. Severe caution should be used before prescribing CRT lenses for children and informed consent should include potential sight-threatening corneal ulcers.

Purpose: To evaluate the recurrence of Thiel-Behnke dystrophy (linked to the 10 q23-q24 locus) after phototherapeutic keratectomy or penetrating keratoplasty., Methods: This is a retrospective study of 4 patients (8 eyes) who underwent phototherapeutic keratectomy and 1 patient (2 eyes) who underwent penetrating keratoplasty. Best corrected visual acuity was assessed, and biomicroscopic examinations for evidence of recurrent dystrophy were documented and photographed. The location, lesion distribution, and lesion pattern of any recurrence was noted., Results: Follow-up ranged from 8 months to 25 years (mean +/- SD 9.7 +/- 7.97 years). All 10 eyes showed biomicroscopic evidence of central recurrence. Six eyes showed an intermediate zone of honeycomb opacities as well as a peripheral zone of focal and geographic lesions. Despite the high incidence of recurrence, functional central visual acuity was maintained. All eyes maintained functional best corrected visual acuity (ranging from 20/25 to 20/80) despite the postoperative recurrence., Conclusion: Recurrence of Thiel-Behnke corneal dystrophy is extremely high after either phototherapeutic keratectomy or penetrating keratoplasty. Despite the high incidence of recurrence, the central cornea is the last to be affected. The peripheral-to-central progression of the lesions points to an epithelial origin for the pathogenesis of the dystrophy. Phototherapeutic keratectomy in the treatment of Thiel-Behnke corneal dystrophy offers a safe and effective treatment modality, providing patients up to 8 years of improved vision ranging from 8 months to 8 years (mean +/- SD 3.7 +/- 2.7 years) and delaying or circumventing the need for more invasive intraocular surgical intervention.

Purpose: To evaluate the effect of expanding the treatment zone of the Nidek EC-5000 laser on postoperative visual acuity as well as night glare and halos after laser in situ keratomileusis (LASIK) using 4 ablation zone diameters., Setting: Division of Ophthalmology, Evanston Northwestern Healthcare and Northwestern University Medical School, Glenview, Illinois, USA., Methods: This prospective study comprised 301 eyes of 154 consecutive patients who had LASIK in 1 or both eyes using the Nidek EC-5000 laser by 1 surgeon with experience in keratomileusis and excimer laser refractive surgery. A 6.5 mm optical zone was used with a transition zone 1.0 mm larger than the pupil under scotopic conditions (7.5, 8.0, 8.5, or 9.0 mm). Targeted correction was calculated according to a customized clinical nomogram. All patients were queried about glare and halos preoperatively and 3 months postoperatively using a questionnaire assigning numeric values to the degree of perceived visual disturbance (0 = no glare or halos, 1 = minimal, 2 = moderate, 3 = severe)., Results: The baseline uncorrected visual acuity (UCVA) was 20/200 or worse in 293 eyes. The baseline best spectacle-corrected visual acuity was 20/20 or better. The mean preoperative refractive sphere was -6.33 diopters (D) +/- 2.80 (SD) (range -1.00 to -16.25 D) and the mean preoperative refractive cylinder, 0.86 +/- 0.83 D (range 0 to +3.25 D). Three months postoperatively, 78% of eyes had a UCVA of 20/20 and 99%, of 20/40 or better. Preoperatively, 94 eyes (31%) had glare and halos. At 3 months, glare, halos, or both were present in 19 eyes of 11 patients (6.3%) (P<.0001); in 14 eyes, patients reported less severe glare and halos postoperatively than preoperatively., Conclusions: The use of a peripheral transition zone 1.0 mm larger than the pupil under scotopic conditions resulted in a low incidence of glare and halos postoperatively and did not adversely affect visual acuity. There was no increase in postoperative complications including corneal ectasia.

Purpose: To report the case of a patient with upper eyelid chronic cicatrizing conjunctivitis and entropion, presumably secondary to ocular rosacea., Methods: Case report and review of medical literature., Results: The patient has a history of chronic cicatrizing conjunctivitis since 1999. Despite an extensive workup for other possible causes, the patient's known history of acne rosacea is the most substantive explanation for her ocular disease., Conclusion: The presence of chronic cicatrizing conjunctivitis affecting mainly the upper eyelids, previously thought to be unique to trachoma, can be associated with ocular rosacea.

Even though ocular surface squamous neoplasia (OSSN) has been recognized for well over a century, the past decade has witnessed advances that have helped rewrite many of the paradigms for the diagnosis and management of these lesions. OSSN occurs predominantly in the elderly for whom they are the third most common oculoorbital tumors after melanoma and lymphoma. In addition to advanced age and male sex, other major risk factors linked to its pathogenesis are ultraviolet light, cigarette smoking, and the human papilloma virus. Although the latter has been linked to OSSN for nearly 4 decades, its identification and role in the pathogenesis of these tumors has been elucidated recently and is addressed in detail in this review. Newer techniques of impression cytology represent a noninvasive and reliable method of diagnosing OSSN and monitoring treated cases. The efficacy of chemotherapeutic agents such as mitomycin C and 5-fluorouracil have been proven in the recent past, making them a clear alternative to the time-tested treatment of surgical excision and cryotherapy. Early reports on the efficacy of topical Iterferon alpha 2b indicate significant promise in providing another alternative for the treatment of some of these neoplasms. These advances thus represent a minimally invasive and highly successful approach to the diagnosis and treatment of OSSN.

Purpose: To report nine cases of tyrosinemia type II, with ocular signs and symptoms., Methods: Participants included nine patients (18 eyes) who were followed for a mean follow-up period of 6.5 years (range, 2 to 8 years). Intervention included dietary restriction of tyrosine and phenylalanine, which led to resolution of ocular and cutaneous lesions, improved behavior in one patient, and may have prevented developmental delay in others. The main outcome measures were visual acuity and serum tyrosine levels to determine the response to dietary therapy. Intelligence testing and developmental screening were performed when appropriate., Results: All patients presented with ocular signs and symptoms as the primary manifestation of disease and serve to illustrate the typical ocular findings of this syndrome. Three patients presented with cutaneous manifestations, and one patient had mild mental impairment at the time of diagnosis., Conclusions: Recalcitrant pseudodendritic keratitis may be the presenting sign in tyrosinemia type II. Awareness of the presenting signs and symptoms may accelerate the diagnosis and dietary intervention. Initiation of a tyrosine-restricted and phenylalanine-restricted diet in infancy is most effective in preventing cognitive impairment.

Over the past quarter century, advances in our understanding of corneal anatomy, physiology, and wound healing have all played an integral role in the management of corneal trauma. As the etiologies of corneal trauma have changed, so has our understanding of the impact of injury on corneal function as it relates to visual rehabilitation. Numerous new classes of antibiotics, antiinflammatory agents, and tissue adhesives have emerged. Occlusive therapy has advanced from simple pressure patching bandage soft contact lenses and collagen shields. Surgical instrumentation, operating microscopes, viscoelastic substances, and suture materials have all improved the outcomes of corneal trauma repair. Improved understanding of the refractive properties of the cornea through topography and alternative suture techniques has helped us restore the natural corneal curvature and visual outcomes. Consequently, in the last quarter of this century our therapeutic approaches to cornea trauma, both medical and surgical, have improved.

Purpose: To describe an alternative, novel surgical approach to the repair of a ruptured globe in the second reported patient with keratoglobus, Ehlers-Danlos type VI, and normal lysyl hydroxylase., Methods: Under general anesthesia, a 360 degrees conjunctival peritomy was performed and the epithelium was removed from the keratoglobus cornea. Descemet's membrane and endothelium were removed from a fresh donor corneoscleral ring. An onlay epikeratoplasty was then performed and the entire donor corneoscleral button was secured to the sclera with 9-0 nylon suture. The conjunctiva was brought into position and tacked down over the edge of the donor graft. After 4 months, a full-thickness penetrating keratoplasty was then performed., Results: The patient ultimately had a ruptured globe in the fellow eye and thus required the identical procedure OU. Both eyes were successfully repaired with a final visual acuity OU of 20/100., Conclusion: The described surgical approach allowed successful surgical repair of bilateral ruptured globes in a patient with keratoglobus, Ehlers-Danlos type VI, and normal lysyl hydroxylase levels. In the previous report of such a patient by Judisch et al. (1), the attempt at surgical repair was unsuccessful and ended in enucleation. The described surgical technique may be used to treat advanced keratoglobus or oculus fragilis.

Purpose: We reviewed the clinical data on 10 obese patients to define the role of obesity as a factor for consideration in planning penetrating keratoplasty., Methods: We performed a retrospective case series review of penetrating keratoplasty in obese patients., Results: In our series of 10 patients, spontaneous extrusion of lens and vitreous (three patients) and choroidal hemorrhage (one patient) were intraoperative complications. Wound leakage, wound dehiscence (two patients), iridocorneal synechia formation, and graft rejection (one patient) were postoperative complications. Despite these complications, seven of the 10 patients achieved a final postoperative visual acuity of > or =20/30., Conclusion: Cornea surgeons must consider obesity as a potential risk factor that may be mitigated partially by careful preoperative patient evaluation, anesthesia planning, and meticulous attention to patient positioning and comfort during surgery.

Purpose: To report staphylococcal endophthalmitis following cataract extraction in a patient with Darier' s disease., Methods: A 67-year-old man presented with decreased visual acuity OD and hypopyon 3 days status post-cataract extraction with intraocular lens placement. The patient was hospitalized and placed on topical and intravenous antibiotics. A diagnostic vitreous tap, pars plana vitrectomy, and intravitreal antibiotic installation were performed., Results: Vitreal tap cultures indicated Staphylococcus epidermidis. His clinical status improved after vitrectomy and antibiotic therapy. The same bacteria was cultured from the patient's eyelids., Conclusions: The source of the S. epidermidis was the skin lesions on the patient's face and eyelids. Darier's disease is an exfoliative hyperkeratotic skin disease that affects all areas on the body except the buttocks. Although clean, sterile surgical techniques were followed, the risk of endophthalmitis following intraocular surgery in a patient with Darier's disease may be increased due to his or her dermatologic condition.

Purpose: To report a case of bilateral corneal ulcers and perforations resulting from hypovitaminosis A in an alcoholic patient., Methods: A 38-year-old cachetic man presented with bilateral corneal ulcerations and severe visual loss. He was hospitalized, developed bilateral corneal perforations, and was treated with bilateral corneal transplants., Results: Serum vitamin A level was 0.01 microg/dL (normal, 0.30-0.75). The electroretinogram was consistent with vitamin A deficiency. His clinical status improved after vitamin A replacement., Conclusions: Although rare in developed countries, the ophthalmologist must consider avitaminosis A in the differential diagnosis of corneal ulcerations in cachetic, alcoholic, or chronically ill patients. Early diagnosis and treatment can prevent unwanted outcomes.

Purpose: To report the use of perfluoropropane (C3F8) gas in the repair of Descemet's membrane detachments., Methods: Descemet's membrane detachments after cataract surgery in three eyes and pars plana vitrectomy in a fourth underwent anterior-chamber gas-exchange descemetopexy with an isoexpansile 14% mixture of C3F8 to facilitate reattachment of Descemet's membrane., Results: Descemet's membrane detachment was successfully reattached after anterior-chamber gas exchange with 14% C3F8 in three of the four eyes treated. The fourth eye treated with 14% C3F8 probably failed Descemet's membrane reattachment because of an unrecognized viscoelastic bleb situated anterior to Descemet's membrane. No corneal decompensation or fluctuations in intraocular pressure were believed to be attributable to isoexpansile C3F8 gas exchange., Conclusion: Early recognition and repair of Descemet's membrane detachments may prevent complications, such as corneal decompensation, corneal opacities and edema, and an overall decline in visual acuity. Isoexpansile C3F8 is demonstrated as a safe and efficacious alternative for the repair of Descemet's membrane detachment.

Purpose: The purpose of the study is to report the outcome and postoperative topographic analysis of seven patients who underwent small-diameter, round, eccentric penetrating keratoplasty., Methods: Seven patients underwent small-diameter, round, eccentric penetrating keratoplasty for a variety of corneal disorders (cataract wound necrosis and dehiscence or fistula, three patients; penetrating keratoplasty wound infection, two patients; corneal rheumatoid melt and perforation, one patient; localized fungal keratitis, one patient). Full-thickness corneal transplants ranged in size from 3.0 to 5.5 mm. The graft wound and sutures spared the visual axis in all cases. Patients were observed for 7 to 42 months (mean, 21 months). All patients had postoperative topographic analysis. One of these also had preoperative analysis., Results: All grafts tectonically were effective in treating the intended condition. Best-corrected visual acuity was 20/30 or better in the four patients without pre-existing corneal transplants or dry eyes; 20/60 and 5/200 in the patients with previous central penetrating keratoplasties; and 20/40 in the patient with rheumatoid melt. There was no clinically significant regular or irregular astigmatism induced centrally by the eccentric graft in the four patients where visual acuity was 20/30 or better. Irregular astigmatism was noted in the other three patients., Conclusion: Small-diameter, eccentric penetrating keratoplasties may be used successfully to treat various peripheral corneal disorders. In some cases, this can be performed without inducing high or irregular astigmatism or both centrally.

This study was conducted to provide experimental information on the probability of syphilis transmission resulting from corneal transplantation. To determine the effects of commonly employed corneal storage conditions on the survival and infectivity of Treponema pallidum, T. pallidum subsp. pallidum (Nichols) was inoculated into OptiSol storage medium or a T. pallidum survival medium at a concentration of 10(6)/ml and incubated in cornea viewing chambers for 24 h at 4 degrees C. When inoculated intradermally into rabbits (0.1 ml per site), none of the 10 sites developed lesions from suspensions incubated in OptiSol in the presence or absence of 100 microgram/ml gentamicin; T. pallidum incubated in the survival medium yielded lesions at one of 10 sites, whereas freshly extracted organisms produced lesions at all 10 sites. In another set of experiments, the infectivity of corneal tissue from rabbits inoculated intratesticularly with 2 x 10(7) T. pallidum 10 days earlier was determined. Corneas from five T. pallidum-infected rabbits were excised, extracted, and tested for infectivity either immediately after removal or after 24-h storage in OptiSol. Recipient rabbits developed lesions at five of 50 intradermal sites when the corneas were neither stored in OptiSol nor rinsed before extraction. Corneas from 10 donor rabbits that were rinsed with phosphate-buffered saline to remove blood and aqueous humor before extraction did not yield lesions at any of 200 sites in the recipient animals. The results of this study indicate that retention of T. pallidum infectivity is poor under typical corneal storage conditions and that rabbit corneal tissue contains few, if any, infectious T. pallidum organisms under the experimental conditions employed.

X-linked ichthyosis is a relatively common oculodermal disorder. Characteristic corneal opacities are small punctate or filiform lesions and are located in the deep corneal stroma. In an unusual case, a 73-year-old man with X-linked ichthyosis and steroid sulfatase deficiency had superficial corneal opacities. The corneal opacities were granular in nature, involving the subepithelial and anterior stromal layers. The opacities resulted in irregular overlying corneal epithelium and were white-gray in color in direct illumination. Histopathologic and electron microscopic studies demonstrated abnormalities of the corneal epithelial basement membrane. The epithelial basement membrane was thickened with irregular extensions into Bowman's layers. Abnormal depositions of basement membrane protein were seen in the anterior stroma. These abnormalities may have resulted from increased production of basement membrane proteins by the corneal epithelium, resulting from hyperactive turnover of the basal layer.

The administration of prophylaxis against tetanus following a corneal abrasion is routinely performed in many acute care facilities, despite a lack of support in the literature for its necessity. The risk of developing clinical tetanus from three different types of injuries to the eye was evaluated in an animal model. Clinical tetanus was induced in unimmunized mice by injecting Clostridium tetani organisms or toxin into the anterior chamber. Immunized mice injected intracamerally did not develop signs of tetanus. Tetanus was not induced by topical inoculation of either live organisms or toxin following corneal epithelial debridement or stromal scarification of unimmunized and immunized mice. The results of this study support the administration of prophylaxis against tetanus following perforating ocular injuries. However, our results do not support its routine use following uncomplicated corneal abrasions or other types of nonperforating ocular injuries.

We noted opaque deposits in SeeQuence disposable contact lenses in three patients with persistent epithelial defects who were being treated with topical ciprofloxacin and prednisolone acetate. In each patient, the contact lenses with deposits were removed and replaced. High performance liquid chromatography analysis revealed the deposits to be precipitates of ciprofloxacin and prednisolone acetate. We incubated new SeeQuence disposable contact lenses in ciprofloxacin, prednisolone phosphate, and prednisolone acetate alone and in combination. Precipitates did form when ciprofloxacin was combined with either prednisolone acetate or prednisolone phosphate. We recommend removal and replacement of contact lenses should these deposits develop to prevent the possibility of corneal toxicity.

Over a 14-year period from 1974 to 1988, 12 eyes of 11 patients with pellucid marginal corneal degeneration underwent penetrating keratoplasty. Peripheral corneal thinning required a large eccentric graft in each case. Follow-up ranged from one to eight years (mean, three years). One graft failed because of a persistent epithelial defect with keratolysis of the wound. Although endothelial allograft rejection was common, occurring in seven of 11 (64%) clear grafts, no graft failed because of rejection. Other complications included retinal detachment and a bacterial corneal ulcer. Suture erosion and vascularization of the graft were not problems. Postoperative spectacle correction was dispensed an average of 11 months after surgery. Visual acuity in seven patients without amblyopia, retinal disease, or a previous corneal ulcer at the time of spectacle correction ranged from 20/20 to 20/40 (mean, 20/30). Average final keratometric astigmatism in these patients was 2.46 diopters (range, 0.00 to 5.25 diopters). We believe that penetrating keratoplasty offers an excellent surgical result for patients with pellucid marginal corneal degeneration.

A retrospective review of 398 eyes of 199 patients with keratoconus revealed 106 eyes of 53 patients with an association between contact lens wear and the development of keratoconus. The absence of keratoconus at the time of contact lens fitting was confirmed by slit-lamp examination, keratometry readings, and manifest refraction. Keratoconus was diagnosed after a mean of 12.2 years of contact lens wear. This group was compared with patients with sporadic keratoconus with either no history of contact lens wear or a history of contact lens wear after the diagnosis. They were older at the time of diagnosis, had central vs decentered cones, and had a tendency toward flatter corneal curvatures. We believe that these patients suggest that long-term contact lens wear is a factor that can lead to keratoconus.

We have used an improved protocol to prepare human, human neonatal, rat and frog lenses for examination by stereo scanning electron microscopy. In this manner, complete and accurate images of the changes in lens cell shape, size and surface complexity are revealed as they differentiate and develop from cuboidal epithelial cells into elongate fiber cells. This method also shows that the apical ends of elongating fibers are variably expanded as they interface with the overlying lens epithelium. Apical ends are most expanded as they contact pre-germinative zone epithelial cells and least enlarged as they contact transitional zone cells. By examining the interlocking devices on opposed fibers in frog, rat and human lenses we determined that there are standard types and interlocking patterns in all lens species. Finally, stereo SEM reveals that the ridges previously reported on aged human nuclear fibers are also seen on human neonatal cortical fibers and that these ridges may actually be interlocked villous or fingerlike projections.

We have discovered cell-to-cell fusion between fiber cells of adult frog lenses in situ. Stereo scanning electron microscopy (SEM) revealed fusion between neighboring fiber cells in radial cell columns (RCCs) and in the same growth ring, respectively. Cell-to-cell fusion of fiber cells in the lens produced fusion zones that in cross-section were larger and of different polygonal shapes than unfused fiber cells. The shape and sizes of fiber cells surrounding fusion zones and the alignment of RCCs were also altered. Serial sectioning through fusion zones confirmed that they were areas of cell-to-cell continuity established by the union of neighboring fiber cells as seen by SEM. Fusion zones represent a previously unrecognized intercellular pathway in the adult frog lens. Although numerous fusion zones were seen throughout the lens cortex and nucleus, cell-to-cell fusion was rarely observed to have occurred between elongating fiber cells. Interestingly, communicating junctions with an unusual ultrastructure that closely resembles the appearance of membranes in the process of fusion demonstrated in other systems were frequently seen in the region of the superficial cortex where fusion zones were most numerous. The fact that such unusual communicating junctions were not found in any other region of the lens leads us to speculate that structural changes in fiber cell communicating junctions may herald the formation of fusion zones and that the initial site of cell-to-cell fusion between fiber cells may be within communicating junctional plaques.

The sutures of the crystalline lens have previously been studied by light microscopy (LM). While the gross suture patterns (umbilical, line, y-shaped and star) of lenses are readily visualized by LM, fiber cell shape, curvature, length and the morphology of fiber cell ends cannot be adequately resolved by this technique. We have used scanning electron microscopy (SEM) to examine the sutures of crystalline lenses. SEM has revealed that in lenses with line, y-shaped or umbilical sutures, the anterior and posterior ends of fiber cells curve away in opposite directions from the polar axis of the lens before interlocking at suture branches. The degree of curvature decreases as a function of the number of suture branches. This relationship was not resolved by LM. SEM has revealed that the relationship of fiber cell taper to suture type was underestimated by previous LM studies. The reduction in fiber cell width from the equator to the sutures is 3:1 and 2:1 respectively, in lenses with line and y-shaped sutures. Furthermore, in lenses with star sutures, fiber cells are flared (1:1.7) rather than tapered, a fact not reported by previous LM studies. SEM also revealed that the offsetting of anterior and posterior suture branches does not result in equal fiber cell length in any growth ring as reported by LM studies. Rather, fiber cell length in any one growth ring varies as a sine wave function according to fiber cell location at the equator. Furthermore, the range of fiber cell length decreases as a function of the number of suture branches. Finally, SEM has revealed that the distal ends of fiber cells are expanded in both width and thickness prior to interlocking at suture branches and that these ends overlap rather than simply abut end-to-end to form a three dimensional suture plane extending down from the lens surfaces to the primary fiber cell mass.

In vivo loops were prepared in the small intestine of rabbits and injected with mixtures of Vibrio cholerae and polystyrene spheres (1.1-micrometers diameter). The loops were removed and frozen after 15 min and then sectioned in a cryostat. The locations of particles and vibrios were determined microscopically. The vibrio/particle ratio was unity in the lumen of the loops, but increased 10-fold in the deep intervillous spaces, indicating active invasion of the mucus gel by the chemotactic parent strain. Motile nonchemotactic mutants and nonmotile mutants of this strain invaded the mucus at the same rate as inert particles. Similar results were obtained with intestinal loops prepared in germfree mice. When germfree mice were disassociated with mixtures of chemotactic (parent or revertant) and nonchemotactic mutant vibrios in equal proportions, the chemotactic strain rapidly outgrew its nonchemotactic counterpart in the intestine. Nonchemotactic mutants introduced as monoassociates into germfree mice were rapidly overgrown by nonmotile mutants which apparently arose spontaneously in the gut. Motility was therefore beneficial to survival only when it was directed by chemotactic stimuli, whereas it was a liability in the absence of such stimuli. Growth of chemotactic vibrios in small intestinal loops of rabbits paralleled that of nonchemotactic mutants for the first 4 to 6 h. Thereafter, the growth rate of the chemotactic vibrios was significantly faster. This was correlated with a significantly higher degree of association with the mucosa on the part of the chemotactic vibrios.