Biochemical and molecular alterations and potential clinical applications of biomarkers in keratoconus.

Keratoconus (KC) is a complex multifactorial corneal ectatic disorder, with disease onset commonly in the second-third decades significantly affecting quantity, quality of vision, and quality of life. Several pathways and factors such as eye rubbing, inflammatory, oxidative, metabolic, genetic, and hormonal among others have been studied in the last two decades. However, the management of KC is still based on a few "one-size fits all" approaches and is predominantly guided by topo/tomographic parameters. Consideration of the several novel factors which have the potential to be biomarkers in addressing several unanswered questions in the disease process could help in the better predictive ability of progression or vision loss and customization of treatment options. This article delves into the understanding of these novel factors or biomarkers based on the pathogenesis of KC and features a special focus on their potential clinical applications and their future role in personalized medicine.

Economic burden and loss of quality of life from dry eye disease in Canada.

OBJECTIVE: To describe the direct and indirect cost estimates of dry eye disease (DED), stratified by disease severity, and the impact of DED on quality of life (QoL) in Canadian patients. METHODS AND ANALYSIS: A prospective, multicentre, observational, cross-sectional study was conducted at six sites across Canada. Eligible patients completed a 20 min survey on demography, general health, disease severity, QoL and direct (resource utilisation and out-of-pocket expenses for the past 3-24 months) and indirect costs (absenteeism and presenteeism based on Work Productivity and Activity Impairment questionnaire responses). Subgroup analyses were performed according to DED severity and presence of Sjögren's syndrome. RESULTS: Responses from 146 of 151 participants were included in the analysis. DED was rated as moderate or severe by 19.2% and 69.2% of patients, respectively. Total mean annual costs of DED were $C24 331 (Canadian dollars) per patient and increased with patient-reported disease severity. Mean (standard deviation [SD]) indirect costs for mild, moderate and severe disease were $C5961 ($C6275), $C16 525 ($C11 607), and $C25 485 ($C22,879), respectively. Mean (SD) direct costs were $C958 ($C1216), $C1303 ($C1574) and $C2766 ($C7161), respectively. QoL scores were lowest in patients with Sjögren's syndrome (8.2% of cohort) and those with severe DED. CONCLUSION: This study provides important insights into the negative impact of DED in a Canadian setting. Severe DED was associated with higher direct and indirect costs and lower QoL compared with those with mild or moderate disease. Increased costs and poorer QoL were also evident for patients with DED plus Sjögren's syndrome versus DED alone.

Pathogenesis of canalicular lacerations.

PURPOSE: To assess the pathogenesis of canalicular lacerations. METHODS: This is a retrospective, clinical case series of 236 patients who sustained a canalicular laceration. All patients who presented to the oculoplastic service of 3 individuals (D.R.J., S.M.G., L.A.M.) from May 1, 1998 to September 30, 2007, with a canalicular laceration were included in the study. Case histories were carefully reviewed in an attempt to classify the mechanism of injury as: "direct (penetrating) injury," "indirect (avulsive)," or "diffuse (avulsive)." Associated injuries (floor fractures, soft tissue lacerations, etc.) were also recorded. RESULTS: Of the 236 patients reviewed, direct canalicular injuries were detected in 128 (54.2%), indirect injuries were detected in 60 (25.4%), and diffuse injuries were detected in 48 (20.3%). Avulsive blunt injuries (due to indirect or diffuse trauma) therefore accounted for 45.7% of the lacerations whereas direct penetrating injuries accounted for 55.2% of the canalicular lacerations. Other injuries associated with the trauma occurred in 152 of the 236 patients (64%). Lacerations involving other portions of the eyelids, periocular area, and face made up the greatest number of associated injuries, and occurred with equal frequency in the direct penetrating group and the indirect/diffuse (avulsive injury) group. Associated injuries more serious in nature including orbital fractures, globe rupture, other body injuries, and head trauma were more commonly seen when diffuse trauma was involved. CONCLUSIONS: Direct, indirect, or diffuse forces may injure canaliculi but direct penetrating injuries were more common than avulsive injuries. More serious injuries (orbital fractures, globe rupture, other body injuries, and head trauma) were more commonly seen when diffuse trauma was involved.

Surgical techniques for the treatment of conjunctivochalasis: paste-pinch-cut conjunctivoplasty versus thermal cautery conjunctivoplasty.

OBJECTIVE: The aim of this study was to evaluate the outcomes of paste-pinch-cut conjunctivoplasty and cautery conjunctivoplasty for the treatment of symptomatic conjunctivochalasis. DESIGN: This was a prospective cohort study. PARTICIPANTS: Sixteen patients (32 eyes) with bilateral conjunctivochalasis that was symptomatic after medical therapy were enrolled in the study. METHODS: This was a single-centre, contralateral eye, prospective study. Paste-pinch-cut conjunctivoplasty was performed in the left eye, and thermal cautery conjunctivoplasty was performed in the right eye. The outcomes of each procedure were compared preoperatively and at the 1-month follow-up by using the Canadian Dry Eye Assessment (CDEA) scoring system, standard conjunctivochalasis grading, and corneal staining. Intraoperative discomfort and immediate postoperative discomfort were assessed by using a 10-point scale. RESULTS: The mean age of patients was 72.4 ± 8.67 years. Conjunctival redundancy was absent in 14 of 16 patients postoperatively. The mean CDEA score improved after both procedures (7.1 ± 2.8 preoperatively versus 4.5 ± 0.78 at the 1-month follow-up for cautery conjunctivoplasty, 7.4 ± 2.5 versus 4.9 ± 3.1 for paste-pinch-cut conjunctivoplasty). This improvement was statistically significant in the cautery conjunctivoplasty group (p = 0.012). Mean intraoperative discomfort was 2.6 ± 2.1 with the use of paste-pinch-cut conjunctivoplasty and 3.5 ± 3.2 with the use of cautery conjunctivoplasty; however, the difference was not statistically significant. No intraoperative or postoperative complications were observed with either technique. CONCLUSIONS: Paste-pinch-cut and thermal cautery conjunctivoplasty are both safe and effective surgical treatments for the repair of conjunctivochalasis, with patients reporting greater improvement in symptoms after the cautery technique.

Patient comfort and visual outcomes of mini-scleral contact lenses.

OBJECTIVE: To evaluate short-term visual outcome, patient acceptance, and tolerance of mini-scleral contact lenses (SCLs) in the management of various corneal pathologies. DESIGN: Retrospective case series. PARTICIPANTS: Thirty-two patients (40 eyes) who received mini-SCLs. METHODS: Single-centre retrospective case series, between February 2010 and January 2013, of 32 patients (40 eyes) with various corneal pathologies who were offered either Maxim 5R, Maxim 7, or Maxim 7 × 11 mini-SCLs for nonsurgical optimization of visual correction. Patients were followed up at 1 and 3 months for assessment of best-corrected visual acuity, comfort, length of daily wear, and complications. RESULTS: Thirty-two patients (40 eyes), with a mean age of 41 ± 16 years, opted to receive mini-SCLs. Eighteen patients had previously undergone surgery such as penetrating keratoplasty, deep anterior lamellar keratoplasty, and intraocular lens implantation. The median best-corrected visual acuity improved from 0.3 logMAR (range 0-1.3) before mini-SCLs, to 0.05 logMAR (range 0-1) with mini-SCLs (p < 0.0001). At 1-month follow-up, the median length of wear was 10 hours/day (range 1.5-15). At 3-month follow-up, the median length of wear was 12 hours/day (range 2-15). All eyes were comfortable at initial use of mini-SCLs and 91% were comfortable at 3-month follow-up. CONCLUSION: Mini-SCLs may be a comfortable management option for patients with keratoconus and other corneal pathologies who are unable to achieve adequate visual outcome with traditional spectacles or rigid gas-permeable contact lenses.

Reactivation of Herpes Zoster Keratitis With Corneal Perforation After Zoster Vaccination.

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.

Dual-purpose corneal tissue for anterior lamellar keratoplasty and Descemet's membrane endothelial keratoplasty.

OBJECTIVE: To assess the intraoperative issues and surgical outcomes of preparing a single-donor corneal tissue for same-day use in both deep anterior lamellar keratoplasty (DALK) and Descemet's membrane endothelial keratoplasty (DMEK). DESIGN: Consecutive retrospective case series. PARTICIPANTS: Ten eyes of 10 patients who underwent DALK (5 patients) or DMEK (5 patients) surgery using dual-purpose corneal tissue. METHODS: Five dual-purpose corneoscleral rims were used to prepare tissue for 5 DMEK and 5 DALK procedures. The submerged cornea using backgrounds away technique was first used to harvest the 5 DMEK grafts, and the remaining tissue was used for the 5 DALK grafts. Tissue preparation and operative use occurred on the same day. Tissue preparation challenges, intraoperative complications, and visual recovery were assessed. RESULTS: There were no difficulties in preparing the 5 dual-purpose tissues, and all 10 lamellar transplants were completed successfully. At the 6-month follow-up, the mean best-corrected distance visual acuity improved from 20/250 to 20/80 in the DALK patients, and from 20/300 to 20/25 in the DMEK patients. Postoperative complications after DALK included retained viscoelastic agent at the interface in 1 patient and a double anterior chamber managed with rebubbling in another. After DMEK, a peripheral partial graft detachment occurred in 1 patient and was managed successfully with rebubbling. All corneas demonstrated clarity on slit-lamp examination. CONCLUSIONS: Single-donor corneal tissue can be effectively used for both DALK and DMEK, and may represent a more efficient use of corneal tissue. Complications with the preparation of dual-purpose tissue were not encountered.

Fibrin glue versus autologous blood for conjunctival autograft fixation in pterygium surgery.

OBJECTIVE: To compare the outcomes between autologous blood- and fibrin glue-fixated conjunctival autografts in pterygium excision surgery. DESIGN: Retrospective case series. PARTICIPANTS: Forty eyes of 40 patients who had a primary nasal pterygium excision. METHODS: A retrospective comparative case series of 40 eyes (40 patients) that had a primary nasal pterygium excision. All eyes had a conjunctival autograft from the superior bulbar conjunctiva to cover the scleral bed. Twenty eyes (20 patients) had fixation of the autograft using autologous blood (AB), and 20 eyes (20 patients) had fixation using fibrin glue (FG). One year of follow-up data included conjunctival graft stability (graft loss, graft retraction), pterygium recurrence, visual acuity, and postoperative complications. Descriptive and inferential statistics were performed. RESULTS: Intraoperatively, no complications occurred in either group. Graft loss occurred in 6 patients in the AB group, compared with none in the FG group. Graft retraction occurred in 3 patients in the AB group and 2 patients in the FG group. At 1 year postoperatively, pterygium recurrence occurred in 4 patients in the AB group and 1 patient in the FG group. One patient in the AB group developed a small pyogenic granuloma that resolved by 6 months with conservative management. Visual acuity remained stable in both groups. CONCLUSIONS: Conjunctival autograft fixation with autologous blood resulted in less stable conjunctival autografts and a higher recurrence rate compared with fixation with fibrin glue.

Accelerated versus standard corneal collagen crosslinking combined with same day phototherapeutic keratectomy and single intrastromal ring segment implantation for keratoconus.

AIM: To compare the results of same day transepithelial phototherapeutic keratectomy (t-PTK) and single inferior intracorneal ring segment (ICRS) combined with standard versus accelerated corneal collagen crosslinking (CXL) for keratoconus. METHODS: All consecutive progressive keratoconus eyes that underwent standard or accelerated CXL treatment preceded by same day t-PTK and placement of a single inferior ICRS and had 6  and 12 months of follow-up were reviewed retrospectively. Eyes were classified into two groups, the 'standard' and the 'accelerated' group, accordingly. Visual, refractive and topographic data prior to surgery and at 6 and 12 months post-treatment were analysed. RESULTS: Sixteen eyes were included in each of the standard and the accelerated groups. Mean patient age was 27.5±8.5 years and 30.5±10.7 years (p=0.38) in the standard and accelerated groups, respectively. There was a significant improvement in uncorrected distance visual acuity, refractive cylinder and all examined corneal parameters in both groups 12 months postsurgery. The corrected distance visual acuity and manifest refraction spherical equivalent showed a significant improvement after 12 months of follow-up only in the accelerated group. However, mean changes in all evaluated parameters did not differ significantly between the two groups. CONCLUSIONS: A combined treatment of accelerated CXL preceded by same day t-PTK and single ICRS is as effective as the combined treatment using standard CXL for visual rehabilitation in progressive keratoconus.

Evaluation of a new technique for preparation of endothelial grafts for descemet membrane endothelial keratoplasty.

PURPOSE: The purpose of this study was to compare the Muraine technique, a relatively new method for preparing endothelial grafts for Descemet membrane endothelial keratoplasty (DMEK), with the current standard submerged cornea using backgrounds away (SCUBA) peeling technique. METHODS: This study was a prospective ex vivo investigation. In a wet-lab setting, 20 donor corneas were prepared for DMEK using The Muraine technique and 20 donor corneas using the SCUBA technique. In each of the technique groups, 10 corneas were prepared by a corneal surgeon and 10 were prepared by a corneal fellow. Primary outcome measures were the time needed to prepare endothelial grafts and the number of graft tears. RESULTS: In the SCUBA technique, median time to prepare grafts was shorter for both the surgeon (301 ± 85 seconds) and fellow (523 ± 58 seconds) compared with the Muraine technique (surgeon, 359 ± 83 seconds; fellow, 543 ± 44 seconds). However, these findings were not statistically significant (surgeon, P = 0.33; fellow, P = 0.24; pooled, P = 0.46). There was a statistically significant difference between surgeon time and fellow time for each technique (SCUBA technique, P = 0.0005; Muraine technique, P = 0.002). In the Muraine technique, there were 5 graft tears (surgeon = 2, fellow = 3), and no graft tears in the SCUBA technique, which was statistically significant (P = 0.047). CONCLUSIONS: The present study demonstrates that the SCUBA technique may be a more effective technique to prepare endothelial donor grafts for DMEK.

Characteristics of patients with ocular cicatricial pemphigoid referred to major tertiary hospital.

OBJECTIVE: To evaluate the demographic and clinical characteristics of patients referred to a tertiary care hospital cornea clinic for ocular cicatricial pemphigoid (OCP) assessment. DESIGN: Retrospective, nonrandomized, consecutive case series. PARTICIPANTS: Thirty three patients with OCP who were treated at the corneal clinic of Toronto Western Hospital from 2003 to 2012. METHODS: Database search of patients from 2003 to 2012 with a referral request or diagnosis of OCP was conducted at a tertiary care hospital cornea clinic. Charts of 33 patients (64 eyes) were reviewed. Outcome measures included patient demographics, methods of diagnosis, visual acuity, ocular features, and disease staging using Foster's staging system, systemic modes of treatment, disease progression, and presence of systemic involvement. RESULTS: Mean patient age at presentation was 69.8 years (range 40-91), and 81% (27/33) were female. At presentation, disease staging consisted of stage I (subepithelial fibrosis) 7.8% (5/64), stage II (shortened fornices) 21.8% (14/64), stage III (symblepharon formation) 65.6% (42/64), and stage IV (keratinization with or without globe immobility) 4.6% (3/64). At the final follow-up visit, the proportions of the involved eyes for stages I to IV were 1.5% (1/64), 10.9% (7/64), 76.5% (49/64), and 10.9% (7/64), respectively. Conjunctival biopsies were obtained from 81% (27/33) of patients and reported as positive in 30% (8/27), negative in 63% (17/27), and inconclusive in 7% (2/27) of patients. Mean duration of follow-up was 6.8 ± 5.6 years (range 0.5-22), and 66.6% (22/33) of patients had progressive disease. Systemic mucocutaneous involvement was noted in 36.3% (12/33) of patients. CONCLUSIONS: The high rate of disease progression suggests the need for improved therapeutic options. Additional modalities are needed in addition to conjunctival biopsy to confirm a diagnosis of OCP in patients with clinical signs of the disease.

Collagen crosslinking after radial keratotomy.

PURPOSE: The aim of this study was to report the outcomes of corneal collagen crosslinking (CXL) after previous radial keratotomy (RK) in patients with decreasing visual acuity and/or diurnal visual fluctuations. METHODS: The charts of all patients who had undergone CXL because of a worsening corrected distance visual acuity (CDVA) and/or diurnal visual fluctuations after RK were reviewed retrospectively. Uncorrected distance visual acuity, CDVA, manifest refraction, and corneal topography were recorded preoperatively and at 1, 3, 6, and 12 months after the procedure. RESULTS: Nine eyes of 6 patients that had undergone an RK 15 to 23 years before the CXL were included in the study. In 5 patients (8 out of 9 eyes), discontinuation of diurnal visual fluctuation was reported between 6 and 12 months after the CXL. The mean uncorrected distance visual acuities pre and 12 months after the CXL were 0.7 logarithm of the minimum angle of resolution (logMAR) and 0.6 logMAR, respectively (P = 0.3). The mean CDVAs pre and 12 months after the CXL were 0.2 logMAR and 0.1 logMAR (P = 0.5), respectively. The mean average keratometry pre and 12 months after the CXL were 40.1 and 39.1 diopters (P = 0.06), respectively. The mean corneal astigmatism values pre and 12 months after the CXL were 2.3 and 1.9 diopters (P = 0.06), respectively. The mean manifest refraction spherical equivalents (MRSEs) before and 12 months after the CXL were +1.4 and +2.5 (P = 0.1), respectively. CONCLUSIONS: CXL is a safe and effective method to restore corneal stability in eyes with a history of RK. However, some of the effect that was achieved at the 6-month visit was blunted at the 12-month visit. Therefore, a longer follow-up is necessary to validate these findings.

EndoGlide versus EndoSerter for the insertion of donor graft in descemet stripping automated endothelial keratoplasty.

PURPOSE: To compare 2 lenticule insertion methods currently in use for Descemet stripping automated endothelial keratoplasty (DSAEK). DESIGN: Prospective randomized single-masked study. PATIENTS AND METHODS: Twenty patients with Fuchs endothelial dystrophy and pseudophakic bullous keratopathy undergoing DSAEK surgery were included and randomized to the use of either EndoGlide or EndoSerter as a delivery method for the donor lenticule. Post surgery, patients were monitored for up to 1 year. Evaluation included corrected distance visual acuity (CDVA) and refraction. Specular microscopy images were obtained at the 6- and 12-month visits. Complications, including rebubbling rate, graft dislocation, and graft failure, were recorded. RESULTS: Twenty eyes were randomized to receive the Tan EndoGlide or the EndoSerter injector for lenticule insertion. Mean patient age was 65.9±8.4 years and 70.3±9.8 years in the Tan EndoGlide and EndoSerter groups, respectively (P=.3). Two eyes in each group needed rebubbling. The mean endothelial cell loss, including the rebubbled eyes, at the 12-month visit was 1093±629 cells/mm2 (range: 239-2109 cells/mm2, mean percentage cell loss 41.2%) and 877±566 cells/mm2 (range: 116-1851 cells/mm2, mean percentage cell loss 31.4%) in the Tan EndoGlide and EndoSerter groups, respectively (P=.45). Mean CDVA did not show a statistically significant difference between the 2 groups at the 6- or 12-month visit. CONCLUSION: The EndoSerter shows comparable results to the Tan EndoGlide. However, further investigation is warranted in order to validate these findings.

Oral buccal mucous membrane allograft with a corneal lamellar graft for the repair of Boston type 1 keratoprosthesis stromal melts.

PURPOSE: To describe a surgical technique to repair Boston type 1 keratoprosthesis (KPro)-related corneal melts. METHODS: Technique description and review of 3 representative cases. RESULTS: After harvesting the buccal mucosa from the patient's inner lower lip, the exposed area of the KPro back plate is prepared for repair by adequate exposure and removal of necrotic tissue. The area is then covered with a lamellar patch of cornea secured in place with interrupted 10-0 nylon sutures, followed by a thin layer of buccal mucosa secured in place with interrupted 8-0 vicryl sutures. CONCLUSIONS: This technique provides surgeons with a method to repair KPro-related corneal melts when there is a conjunctival deficiency.