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PURPOSE: To compare the efficacy and safety of a preservative-free, multi-ingredient formulation of carboxymethylcellulose 0.5%, hyaluronic acid 0.1%, and organic osmolytes (CMC-HA), to preservative-free carboxymethylcellulose 0.5% (CMC) in the management of postoperative signs and symptoms of dry eye following laser-assisted in situ keratomileusis (LASIK). METHODS: This was a double-masked, randomized, parallel-group study conducted in 14 clinical centers in Canada and Australia. Subjects with no more than mild dry eye instilled CMC-HA or CMC for 90 days post-LASIK. Ocular Surface Disease Index© (OSDI; primary efficacy measure), corneal staining, tear break-up time (TBUT), Schirmer's test, acceptability/tolerability surveys, and visual acuity were assessed at screening and days 2, 10, 30, 60, and 90 post-surgery. Safety analyses included all enrolled. RESULTS: A total of 148 subjects (CMC-HA, n=75; CMC, n=73) were enrolled and assigned to receive treatment, and 126 subjects completed the study without any protocol violations. Post-LASIK, dry eye signs/symptoms peaked at 10 days. OSDI scores for both groups returned to normal with no differences between treatment groups at day 90 (P=0.775). Corneal staining, Schirmer's test, TBUT, and survey results were comparable. Higher mean improvements in uncorrected visual acuity were observed in the CMC-HA group at all study visits, reaching statistical significance at day 30 (P=0.013). Both treatments were well tolerated. CONCLUSION: CMC-HA-containing artificial tears relieved post-LASIK ocular dryness as well as CMC alone, and demonstrated incremental benefit in uncorrected vision, with a favorable safety profile. Results support use of CMC-HA eye drops to reduce signs and symptoms of ocular dryness post-LASIK.

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PURPOSE: We present a case of reactivated herpes zoster keratouveitis of 6 years duration with corneal perforation requiring penetrating keratoplasty shortly after inoculation with herpes zoster vaccine (Zostavax, Merck, Quebec, Canada). METHODS: Retrospective case report. RESULTS: A 67-year-old woman with a 5-year history of recurrent unilateral herpes zoster keratouveitis in her right eye presented with another recurrence 2 weeks after Zostavax vaccination. Three months later, she developed descemetocele and 2 months afterward, corneal perforation, which was managed by penetrating keratoplasty. Immunohistopathological examination disclosed positive staining for varicella zoster virus in most of the keratocytes adjacent to the descemetocele and perforation, most vividly in the deeper two-thirds of the stroma where the keratocytes were most dense, but not in corneal epithelium or endothelium. Electron microscopic examination showed universally severely degenerated corneal keratocytes in the corneal stroma adjacent to the perforation with variable numbers of herpes virus capsids present in half of these cells. Only a rare normal-appearing keratocyte was identified in the more peripheral corneal stroma. CONCLUSIONS: We present a case of reactivation of herpes keratouveitis shortly after vaccination with Zostavax in a patient with previous herpes zoster ophthalmicus. We demonstrate, for the first time, ultrastructural evidence consistent with inactive virus capsids in diffusely degenerated keratocytes in the extracted corneal tissue.

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PURPOSE: To compare the long-term visual outcomes of patients with keratoconus treated with either phototherapeutic keratectomy (PTK) or mechanical epithelial removal before corneal collagen cross-linking (CXL) at 1, 3, 6, and 12 months postoperatively. METHODS: CXL was performed by 1 of 3 surgeons (K.B., W.B.J., or G.M.). Seventeen eyes underwent mechanical epithelial removal before CXL and were consecutively selected after being matched with the 17 eyes in the PTK group for the variables of procedure date, average keratometry, and pachymetry. All cones were central. Manifest refraction spherical equivalent, sphere, cylinder, corrected distance visual acuity (CDVA), and pachymetry were measured and compared preoperatively and in follow-up. RESULTS: The mean CDVA change in the PTK group at 12 months postoperatively was statistically different from the mean CDVA change in the mechanical group at 12 months postoperatively (P = 0.031). The PTK group had significantly better outcomes in visual acuity 12 months postoperatively than did the mechanical group (P > 0.05). The mean number of lines of improvement in the PTK and mechanical groups were 2.30 ± 0.96 and 0.00 ± 0.33 lines, respectively (P = 0.0036). The mean change between the preoperative and 12 months postoperative manifest refraction spherical equivalent for the PTK and mechanical groups were 0.78 ± 0.65 and 0.17 ± 0.65, respectively (P > 0.05). CONCLUSIONS: PTK CXL resulted in better visual outcomes in comparison with mechanical epithelial removal CXL 1 year after treatment.

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We developed cell-free implants, comprising carbodiimide crosslinked recombinant human collagen (RHC), to enable corneal regeneration by endogenous cell recruitment, to address the worldwide shortage of donor corneas. Patients were grafted with RHC implants. Over four years, the regenerated neo-corneas were stably integrated without rejection, without the long immunosuppression regime needed by donor cornea patients. There was no recruitment of inflammatory dendritic cells into the implant area, whereas, even with immunosuppression, donor cornea recipients showed dendritic cell migration into the central cornea and a rejection episode was observed. Regeneration as evidenced by continued nerve and stromal cell repopulation occurred over the four years to approximate the micro-architecture of healthy corneas. Histopathology of a regenerated, clear cornea from a regrafted patient showed normal corneal architecture. Donor human cornea grafted eyes had abnormally tortuous nerves and stromal cell death was found. Implanted patients had a 4-year average corrected visual acuity of 20/54 and gained more than 5 Snellen lines of vision on an eye chart. The visual acuity can be improved with more robust materials for better shape retention. Nevertheless, these RHC implants can achieve stable regeneration and therefore, represent a potentially safe alternative to donor organ transplantation.

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PURPOSE: To evaluate the visual and refractive outcome for four wavefront-guided surface ablation (WGSA) techniques (LASEK, LASEK flap-off [LASEK FO], Epi-LASIK, and Epi-LASIK flap-off [Epi-LASIK FO]) in a large myopic population. METHODS: This retrospective review included 1000 myopic eyes (spherical equivalent [SE] -1.0 to -8.0 diopters [D]) treated with WGSA (VISX STAR S4 with IR) using four different epithelial management techniques. Flaps were either retained (163 Epi-LASIK, 361 LASEK) or discarded (277 Epi-LASIK FO, 199 LASEK FO). Eyes in each group were stratified to either low, mild, moderate, or high myopia based on preoperative SE. Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), manifest refraction spherical equivalent (MRSE), predictability, lines lost, and haze were compared at 3, 6, and 12 months. RESULTS: At 1 year, UDVA and CDVA of ≥20/20 and 20/15 were comparable across the four procedure groups and within each subgroup of myopia. Predictability was less than or equal to ±0.5 D of intended correction in 96% to 99% of eyes. LASEK FO and Epi-LASIK FO outperformed the EPI-LASIK in achieved MRSE, especially in the high myopia category (-0.012, 0.040, and -0.27 D, respectively, P < 0.05). No eyes lost more than one line of CDVA; and 50% to 60% of eyes in each group gained one or more lines. No significant haze was recorded in any group. There was no statistically significant difference between groups in the preoperative MRSE and efficacy indices except for LASEK FO. CONCLUSIONS: At 1 year, there was no statistically significant difference in visual outcomes between techniques for any degree of myopia. However, the MRSE achieved with LASEK FO and Epi-LASIK FO were closer to emmetropia.

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OBJECTIVES: To characterize the clinical presentations, features, and outcomes of eyelash alopecia areata. DESIGN: Retrospective chart review of patients evaluated for eyelash loss and found to have eyelash alopecia areata. A 3-year follow-up was required. PARTICIPANTS: The study involved 15 patients. METHODS: Patients who presented at a tertiary care eye clinic for evaluation of eyelash loss and were found to have eyelash alopecia areata were reviewed. Demographic considerations were categorized; they included age at presentation, areas of other hair loss, other relevant history, and treatment responses. RESULTS: Patients were young (mean age 18 years) and had a large female predominance (female-to-male ratio, 14:1). Concurrent scalp and brow involvement, either in isolation (20% and 13%, respectively) or together (13%), were seen in half of the patients (46%). Upper eyelid involvement was more common and severe than lower eyelid involvement, and 40% of patients experienced complete regrowth of lashes, with a mean time to regrowth of 28 months (range, 6 to 60 months). Of these, 13% experienced partial regrowth. Younger age at presentation was associated with regrowth, whereas presence or absence of other involved sites, personal or family histories of atopy, family history of alopecia, other autoimmune diseases, or the use of topical steroids did not appear to affect prognosis. CONCLUSIONS: Eyelash alopecia areata is a unique entity, although it remains potentially underdiagnosed. The key differential diagnosis is trichotillomania, which is commonly associated with obsessive-compulsive disorders. The presence of exclamation-mark hairs in alopecia areata plays an important role in differentiating the 2 diagnoses.

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OBJECTIVE: To compare the visual outcomes of patients with keratoconus treated with either phototherapeutic keratectomy (PTK) or mechanical epithelial removal prior to corneal collagen crosslinking (CXL). DESIGN: Comparative study. PARTICIPANTS: The records of 34 patients (34 eyes) who had PTK (17 eyes) or mechanical (17 eyes) epithelial removal prior to CXL for keratoconus were reviewed retrospectively. METHODS: CXL was performed by 1 of 3 surgeons (G.M., W.B.J., or K.B.). Of the eyes, 17 had undergone mechanical epithelial removal prior to CXL and were consecutively selected, after matching with the 17 eyes in the PTK group, for the variables of procedure date, average keratometry, and pachymetry. All eyes had central cones. Manifest refraction spherical equivalent, sphere, cylinder, best-corrected distance visual acuity, and pachymetry were measured and compared preoperatively and in follow-up. RESULTS: The mean change between the pre- and postoperative manifest refraction spherical equivalent for the PTK and mechanical groups was 1.68 ± 0.80 and 0.26 ± 0.90, respectively (p < 0.05). The mean change between pre- and postoperative cylinder for the PTK and mechanical groups was 0.53 ± 0.28 and 0 ± 0.18, respectively (p < 0.05). The mean number of lines of improvement in the PTK and mechanical groups were 0.33 ± 0.82 and -0.58 ± 0.45 lines, respectively (p > 0.05). CONCLUSIONS: Early results suggest that CXL with laser epithelial removal is superior to CXL with mechanical epithelial removal because it reduces refractive error in qualified patients. Although not statistically significant, there was also a trend for PTK CXL patients to have better visual outcomes.

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OBJECTIVE: To evaluate the change of ocular and corneal higher order aberrations (HOAs) after wavefront-guided advanced surface ablation (WF-ASA) for myopia using 4 different epithelial management techniques (AA-PRK, LASEK, Epi-PRK, and Epi-LASIK). DESIGN: Retrospective single centre excimer database analysis. PARTICIPANTS: Two hundred and forty eyes equally divided between the 4 WF-ASA techniques, matched for mean and range of required spherical correction. METHODS: Ocular wavefront aberrations were measured using the wavescan aberrometer and corneal aberrations were obtained from corneal topography elevation maps and calculated by ray-tracing. All data were collected preoperatively and 3 months following treatment. The aberrations were described as Zernike polynomials, and analysis focused on total HOAs and spherical aberration (SA). RESULTS: Three months postoperatively, there was a statistically significant surgically induced increase in total HOAs and SA both for ocular and corneal analysis (p < 0.001). There was no statistically significant difference in the induced ocular SA and HOAs between the groups, but the differences in induced corneal SA and HOAs were significant (p < 0.010). Ocular changes in SA were weakly correlated to preoperative SA (20.30, p < 0.001) but strongly correlated to applied spherical correction (20.68, p < 0.001). Surgically induced corneal SA was weakly correlated to preoperative corneal SA (20.34, p < 0.001) and applied spherical correction (20.46, p < 0.001). CONCLUSIONS: Three months postoperatively, all procedures resulted in an increase in ocular and cornealHOAs and SA. Induced aberrations were most strongly correlated to the applied spherical power correction. Modifying the existing ablation pattern to compensate for induced HOAs might improve the outcome.

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PURPOSE: To evaluate an aspheric ablation profile to improve near vision in presbyopic patients with hyperopia and to outline the key factors of success. METHODS: A prospective, nonrandomized, clinical trial of 66 eyes of 33 hyperopic patients who underwent customized bilateral refractive surgery, which included an aspheric presbyopia treatment shape and wavefront-driven hyperopic treatment, was studied. Surgeries were performed using the VISX STAR S4 or STAR S4 IR excimer laser system (Abbott Medical Optics). Mean preoperative refractive error was +1.77 ± 0.56 diopters (D) sphere (range: 0.75 to 3.50 D) with 0.41 ± 0.34 D cylinder (range: 0.00 to 1.50 D). All patients received full distance refractive correction. No patients received monovision or were intentionally left with residual myopia. Patient satisfaction results were evaluated using a questionnaire with a 5-point scale. RESULTS: Sixty eyes completed 6-month and 50 eyes completed 12-month postoperative follow-up. At 6 months, mean corrected distance visual acuity (CDVA) was 20/20±1 line (range: 20/25 to 20/10). Mean gain in distance-corrected near visual acuity (DCNVA) was 2.7 ± 1.7 lines with a maximum of 6 lines of near. Spectacle dependence for tasks, such as reading and computer use, was reduced. At 12 months, 100% of patients had achieved binocular simultaneous uncorrected vision of 20/25 or better and J3. Refraction was stable over 12 months. Contrast sensitivity reduction was clinically insignificant (1 step or 0.15 logCS). Negative spherical aberration highly correlated with postoperative improvement of DCNVA. Patients who had a larger amount of preoperative hyperopia or a greater decrease of preoperative DCNVA were more likely to have overall satisfaction. CONCLUSIONS: The aspheric ablation designed to expand near functional vision was effective and stable over 12 months. The wavefront-customized hyperopic treatment significantly reduced spectacle dependence.

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PURPOSE: To determine the correlations between mean keratometry (KM), central corneal thicknesses (CCT), and cycloplegic spherical equivalent (SE) in patients with a wide range of ametropia. METHODS: Retrospective analysis of the excimer laser surgery database at the University of Ottawa Eye Institute between 1993 and 2008 was performed. This study included 3395 eyes from 1858 subjects. The refractive error ranged from +6.75 to -14.00 D. CCT was obtained either by ultrasound pachymetry or anterior segment tomography. Keratometry was determined using an autokeratorefractometer. RESULTS: In the myopic group, the SE was observed to be inversely proportional to the KM (correlation coefficient, -0.18; P < 0.01). The KM and CCT were also inversely proportional (-0.11; P < 0.01). In hyperopes, a correlation between the cycloplegic SE and KM was also found (-0.25; P < 0.01), but the CCT did not correlate with either of these metrics. A direct correlation for the myopic group was found between KM and the difference in power of the principal meridians (keratometric astigmatism [KA]) (0.08; P < 0.01). This relationship was not observed for the hyperopic group. Within the myopic group the SE correlated with the refractive astigmatism (RA) (-0.04; P = 0 0.04). In all groups, a strong correlation was observed between RA and KA (0.78; P < 0.01). CONCLUSIONS: In the myopia group, the KM showed close correspondence with KA and an inverse relationship with SE and CCT. In hyperopes, an inverse correlation between the KM and SE was found, but no correlation with CCT was evident.

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BACKGROUND/AIMS: To study the changes in wavefront (ocular) and corneal higher order aberrations (HOAs) and visual acuity (VA) outcome following wavefront-guided advanced surface ablation (ASA) techniques and intralase femtosecond LASIK (iLASIK) in myopia treatment. METHODS: Ocular aberration and corneal topography of 240 eyes in the ASA techniques (this was equally divided into a flap-on group where the epithelial flap was preserved and reapplied to the photoablated stromal bed and a flap-off group when the epithelial flap was discarded during the procedure), and 138 eyes in the iLASIK group were obtained before and 3 months following treatment. The correlation of aberrations with best spectacle-corrected visual acuity was analyzed. RESULTS: At 3 months, there was statistically significant (P < 0.001) surgically induced increase in spherical aberration (SA) in each of the techniques for both ocular and corneal analysis. iLASIK induced significantly less ocular and corneal HOAs (P < 0.001). The mean manifest refractive spherical equivalent was closer to attempted correction compared to other groups (P < 0.001). Eighty-three eyes (70%) of flap-on, 80 (67%) flap-off and 94 eyes (68%) in the iLASIK group achieved 20/20 uncorrected VA. Fifteen eyes (11%) accomplished 20/12.5 or better in iLASIK compared to 4 (3%) for flap-on and 7 (6%) for flap-off ASA group. Only the flap-off treatment showed a consistent correlation between the corrected aberrations and visual performance. CONCLUSION: At 3 months, all procedures resulted in a significant increase in HOAs and SA. All had comparable 20/20 VA and 11% of iLASIK patients achieved 20/12.5 or better level.

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Corneas from human donors are used to replace damaged tissue and treat corneal blindness, but there is a severe worldwide shortage of donor corneas. We conducted a phase 1 clinical study in which biosynthetic mimics of corneal extracellular matrix were implanted to replace the pathologic anterior cornea of 10 patients who had significant vision loss, with the aim of facilitating endogenous tissue regeneration without the use of human donor tissue. The biosynthetic implants remained stably integrated and avascular for 24 months after surgery, without the need for long-term use of the steroid immunosuppression that is required for traditional allotransplantation. Corneal reepithelialization occurred in all patients, although a delay in epithelial closure as a result of the overlying retaining sutures led to early, localized implant thinning and fibrosis in some patients. The tear film was restored, and stromal cells were recruited into the implant in all patients. Nerve regeneration was also observed and touch sensitivity was restored, both to an equal or to a greater degree than is seen with human donor tissue. Vision at 24 months improved from preoperative values in six patients. With further optimization, biosynthetic corneal implants could offer a safe and effective alternative to the implantation of human tissue to help address the current donor cornea shortage.

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Dry eye complaints are common, have a diverse etiology, and result from disruption of the normal tear film; hence, the term "dysfunctional tear syndrome." Recent research has shown that ocular surface disorders have an inflammatory origin, that inflammation of the ocular surface does not always manifest as "red eye," and that a patient does not have to have a systemic autoimmune disease to experience a local, ocular autoimmune event. A panel of Canadian cornea and external disease subspecialists met and developed a questionnaire and treatment algorithm to aid the comprehensive ophthalmologist. Management of ocular surface disorders begins with a review of the patient's medical history, with particular attention to medication use, and a thorough ophthalmological examination. Use of a simple questionnaire can aid in the diagnosis. A variety of treatment modalities are available, the most effective of which are those that target the underlying inflammatory process with the goal of restoring the normal tear film. A treatment algorithm is presented that matches the severity of symptoms with the intensity of treatment. Lifestyle modifications, regular hygiene, and tear supplements may be sufficient in patients with mild symptoms. Anti-inflammatory medications (topical cyclosporin A, short courses of topical steroids, and [or] oral tetracyclines) and physical measures (punctal plugs, moisture-retaining eye wear) are implemented for those with moderate-to-severe symptoms. Autologous serum tears, scleral contact lenses, and surgery are reserved for patients with severe symptoms who have an unsatisfactory response to anti-inflammatory medications. Patients with lid disease or rosacea and those with allergic conditions should be identified during the initial encounter and should receive specific therapy to relieve their symptoms.

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BACKGROUND: The aim of this article is to present a consensus on the appropriate identification and management of patients with blepharitis based on expert clinical recommendations for 4 representative case studies and evidence from well-designed clinical trials. METHODS: The case study recommendations were developed at a consensus panel meeting of Canadian ophthalmologists and a guest ophthalmologist from the U.K., with additional input from family doctors and an infectious disease/medical microbiologist, which took place in Toronto in June 2006. A MEDLINE search was also conducted of English language articles describing randomized controlled clinical trials that involved patients with blepharitis. RESULTS: Blepharitis involving predominantly the skin and lashes tends to be staphylococcal and (or) seborrheic in nature, whereas involvement of the meibomian glands may be either seborrheic, obstructive, or a combination (mixed). The pathophysiology of blepharitis is a complex interaction of various factors, including abnormal lid-margin secretions, microbial organisms, and abnormalities of the tear film. Blepharitis can present with a range of signs and symptoms, and is associated with various dermatological conditions, namely, seborrheic dermatitis, rosacea, and eczema. The mainstay of treatment is an eyelid hygiene regimen, which needs to be continued long term. Topical antibiotics are used to reduce the bacterial load. Topical corticosteroid preparations may be helpful in patients with marked inflammation. INTERPRETATION: Blepharitis can present with a range of signs and symptoms, and its management can be complicated by a number of factors. Expert clinical recommendations and a review of the evidence on treatment supports the practice of careful lid hygiene, possibly combined with the use of topical antibiotics, with or without topical steroids. Systemic antibiotics may be appropriate in some patients.

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PURPOSE: To report a non-contact lens wearer with persistent Acanthamoeba organisms in the cornea after being treated with medical therapy that included topical chlorhexidine as 1 agent for 1 year. METHODS: A 53-year-old man with Acanthamoeba keratitis was treated with medical therapy for >1 year, followed by a penetrating keratoplasty. RESULTS: Histopathologic examination of the keratoplasty specimen revealed viable-appearing Acanthamoeba cysts and trophozoites within the deep corneal stroma in a focus of corneal scarring. CONCLUSIONS: The use of chlorhexidine as 1 agent in the medical management of Acanthamoeba keratitis may not eradicate the organisms.

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