Impact of the use of anti-glaucoma medications on the risk of herpetic keratitis recurrence.

PURPOSE: Numerous case reports have associated anti-glaucoma medications with recurrence of herpes simplex virus (HSV) and herpes zoster virus (HZV) keratitis. The aim of our study was to determine whether different anti-glaucoma agents are associated with recurrence of herpetic keratitis. METHODS: This was a retrospective cohort study using health databases from a Canadian province from January 2001 to December 2012. A new cohort of users on topical prostaglandins (PGs), beta blockers (BBs), alpha-2 agonists (AAs) and carbonic anhydrase inhibitors (CAIs) was created. The date of the third anti-glaucoma drug dispensation within 90 days was deemed the index date of the case. Herpetic keratitis events, as defined by an ICD-9/10 code for HSV or HZV keratitis, or the dispensation of an anti-viral medication by either an ophthalmologist or an optometrist, were examined prior to and following the index date. Risk ratios (RRs) were computed to compare the risk of HSV/HZV keratitis among the PG, BB, AA, and CAI groups individually and collectively while adjusting for age and sex. RESULTS: Among 19,986 users of glaucoma medications identified, there were 684 cases of HSV/HZV keratitis. There was no increased risk of HSV/HZV keratitis recurrence for any of the four glaucoma medications classes individually or collectively when adjusted for age and sex. There was also no increased risk for redeveloping either HSV keratitis only or HZV keratitis only amongst all anti-glaucoma users. CONCLUSION: There is no association between the use of topical ocular hypotensive therapies and HSV/HZV keratitis recurrence. Further studies are needed to confirm these findings.

Thygeson's superficial punctate keratitis.

PURPOSE: Thygeson's superficial punctate keratitis (TSPK) is a chronic and recurrent corneal epitheliopathy. Although first described more than 70 years ago, the precise etiological mechanism and optimal treatment approach for TSPK has not been established. In this paper, we present an up-to date review of the literature and propose a step-by-step management protocol. METHOD: A literature search was done on PubMed using keywords including Thygeson's superficial punctate keratitis, punctate keratitis, etiology, management, and treatment. The literature was reviewed and reported. RESULTS: The main findings of this review include a summary of the main theories behind the cause TSPK; although topical corticosteroids remain the treatment of choice, long-term risks associated with these agents and recent studies have revealed immunomodulatory agents as promising treatment adjuvants or alternatives for TSPK; surgical interventions such as PRK/PTK have been utilized in selected refractory cases; finally we propose a treatment protocol based the best available evidence and clinical experience. CONCLUSION: Although the clinical features of TSPK have been well described, the specific cause of TSPK remains inconclusive. Mechanisms proposed including viral infection, immune-mediated, and immune responses to viral infection but require further investigation. More prospective randomized clinical trials comparing efficacy of corticosteroids, tacrolimus, and cyclosporine A (CSA) are required. More evidence is required for surgical interventions such as PRK/PTK.

Neurotrophic keratopathy as a complication of scleral fixated intraocular lens implantation.

PURPOSE: To report a series of patients who developed neurotrophic keratopathy following scleral fixation of intraocular lenses. METHODS: Retrospective case series of patients undergoing implantation of scleral fixated IOLs with various techniques. RESULTS: Three patients developed NK in the immediate post-operative period following scleral fixation of IOLs. Scleral fixation of IOL was performed using three different techniques (4-point fixation, "Yamane" flanged intrascleral and tunneled intrascleral haptic fixation). None of the patient had any prior risk factors for the development of NK. In all patients, intrascleral haptics or scleral sutures were positioned on the horizontal meridian. All patients also underwent light peripheral retinal endolaser. CONCLUSIONS: NK can rarely occur following scleral fixation of IOLs. The combination of suturing or intrascleral fixation of the IOL on the horizontal meridian and peripheral retinal endolaser may synergistically damage to the long ciliary nerves with a "two-hit" mechanism and cause NK.

Lamellar macular holes: surgical outcome of 106 patients with long-term follow-up.

PURPOSE: To determine long-term results of vitrectomy for lamellar macular holes (LMH). To evaluate how the type of lamellar macular hole (tractional vs. degenerative) and the crystalline lens status might influence visual outcomes. METHODS: We collected data from 106 patients with symptomatic lamellar macular hole that underwent pars plana vitrectomy with membranectomy and internal limiting membrane peeling. Best-corrected visual acuity (BCVA) and optical coherence tomography appearance were determined preoperatively and postoperatively. RESULTS: Most of the lamellar holes were of tractional type (65%). Mean follow-up after surgery was 36 months. Mean BCVA increased from 20/50 to 20/43 at 6 months and 20/33 at last follow-up visit (p < 0.001). Vision improved in 74 (70%), remained stable in 11 (10%), and decreased in 21 (20%) eyes. Subgroup analysis showed that visual acuity significantly increased in the tractional but not in the degenerative forms of LMH. Thirteen eyes lost two or more ETDRS lines after surgery. Preoperative phakic/pseudophakic status influenced the functional outcomes. CONCLUSIONS: Surgery may be effective in some subsets of patients with lamellar macular hole, but postoperative visual loss is not uncommon and prospective controlled studies are warranted.

Human papillomavirus (HPV)-associated trilateral squamous neoplasia in immunocompetent individual.

PURPOSE: To describe a case of bilateral conjunctival and cervical human papillomavirus (HPV)-related squamous neoplasia. CASE DESCRIPTION: A healthy immunocompetent 55-year-old lady came to our attention for prosecution of care of a right recurrent conjunctival squamous cell carcinoma. Upon examination, she was found disease-free in the right eye but displayed a left conjunctival intraepithelial neoplasia (CIN grade I) and low-grade cervical squamous dysplasia. HPV infection with genotypes 16 (right eye), 11 and 39 (left eye) and 39 (uterine cervix) was also detected. CONCLUSION: Simultaneous uterine and conjunctival HPV-related squamous neoplasia can occur in immunocompetent individuals. Auto-inoculation and repeated exposure to HPV could explain coexistence of different genotypes.

Cysticidal activity of antifungals against different genotypes of Acanthamoeba.

Antifungal drugs have been proposed as a novel treatment for Acanthamoeba keratitis. The cysticidal activity of several antifungal compounds was tested against different genotypes of culture collection and clinical isolates of Acanthamoeba. Only voriconazole and posaconazole were found to be cysticidal, with no differences in activity observed between clinical and culture collection isolates.

Acanthamoeba sclerokeratitis: epidemiology, clinical features, and treatment outcomes.

PURPOSE: To describe the epidemiology, clinical features, and treatment outcomes of Acanthamoeba sclerokeratitis (ASK). DESIGN: Retrospective case series. PARTICIPANTS: All cases of both Acanthamoeba keratitis (AK) and ASK identified between January 1, 2000, and January 8, 2011, at Moorfields Eye Hospital. METHODS: Acanthamoeba keratitis was defined as the presence of AK with concurrent ipsilateral scleral inflammation. Topical steroids and oral nonsteroidal anti-inflammatory drugs (NSAIDs) were used as the first line of treatment. In unresponsive cases, oral NSAIDs were replaced by oral prednisolone with cyclosporine, azathioprine, or mycophenolate as steroid-sparing agents. Cyclosporine was combined with azathioprine or mycophenolate in cases unresponsive to only 1 of these drugs alone. MAIN OUTCOME MEASURES: Epidemiology, clinical phenotype, response to therapy, resolution of inflammation, visual outcome, corneal transplantation, and enucleation rate. RESULTS: From a series of 178 patients with AK, 36 eyes of 33 patients (18.5%) developed ASK. A total of 25 of 33 patients (76%) with ASK were tertiary referrals. The incidence of the disease in greater London was 0.13 per million, and the incidence in this population of patients with AK was 33 of 178 (18.5%). Mild scleritis/limbitis responsive to topical steroids and oral NSAIDs was present in 11 of 36 eyes (31%), and moderate/severe scleritis, requiring systemic immunosuppressive therapy, was present in 25 eyes (69%). Before the initiation of ASK treatment, 2 of 36 eyes (6%) had corrected distance visual acuity (CDVA) ≥ 20/40. The length of ASK treatment was 15.3 ± 20.7 months. The follow-up after discontinuation of scleritis treatment was 27.2 ± 31.8 months. An improvement in visual acuity was recorded in 23 of 36 eyes (64%). At the final visit, 13 of 36 eyes (36%) had CDVA ≥ 20/40. Control of scleral inflammation and pain was achieved in all but 2 eyes (2 enucleations). Cataract developed in 10 of 36 eyes (28%), and 14 of 36 eyes (39%) developed a persistent epithelial defect. Keratoplasty was performed in 21 of 36 eyes (58%), 9 therapeutic/tectonic and 12 for visual rehabilitation. Six eyes had more than 1 keratoplasty. The mild scleritis group had better outcomes in terms of visual improvement and need for keratoplasty. CONCLUSIONS: Acanthamoeba sclerokeratitis is associated with poor clinical outcomes. Management of ASK with anti-inflammatory/immunosuppressive treatment is usually effective in reducing both scleral inflammation and symptoms and possibly reduces the number of enucleations.

Outcomes of Descemet Stripping Only Without Postoperative Use of Topical Rho-associated Protein Kinase Inhibitors.

PURPOSE: Descemet Stripping Only (DSO) is a promising surgical option for select patients with Fuchs endothelial dystrophy (FED). There is growing support for the use of topical Rho-associated protein kinase inhibitors (ROCKi) to optimize DSO outcomes. However, in many settings, ROCKi are either unavailable or not approved to treat corneal diseases. This study sought to characterize patient outcomes after DSO in the absence of ROCKi and potentially broaden the settings where DSO can be offered to patients. METHODS: Single-center retrospective case series of 15 eyes/11 patients (66 years; 52-74) that underwent DSO, alone or combined with cataract surgery, by one surgeon between August 2020 and January 2023. Patients included in analyses had FED with central guttae, no clinical evidence of corneal edema, and a clinically healthy peripheral corneal endothelium. RESULTS: Mean follow-up time was 14 months (2-34). Fourteen of 15 eyes achieved corneal clearance (93.3%). Mean time to clearance was 8.5 weeks (3-23). Eleven eyes (73%) achieved corrected distance visual acuity of ≤0.2 with a significant postoperative improvement at 4 to 8 months (P < 0.05) and sustained improvements at >12 months. No significant astigmatism was introduced by the procedure. Two eyes developed cystoid macular edema postoperatively. A trend toward earlier clearance was observed in the <65 years old group. CONCLUSIONS: Despite a longer time to corneal clearance in this cohort compared with the few studies using ROCKi, the overall success rate and visual outcomes for the patients in our cohort supports the use of DSO in settings where ROCKi are not readily available.

Predicting Long-Term Endothelial Cell Loss after Preloaded Descemet Membrane Endothelial Keratoplasty in Fuchs' Endothelial Corneal Dystrophy: A Mathematical Model.

(1) Background: This study offers a biexponential model to estimate corneal endothelial cell decay (ECD) following preloaded "endothelium-in" Descemet membrane endothelial keratoplasty (DMEK) in Fuchs' endothelial corneal dystrophy (FECD) patients; (2) Methods: A total of 65 eyes undergoing DMEK alone or combined with cataract surgery were evaluated. The follow-up period was divided into an early phase (first 6 months) and a late phase (up to 36 months). Endothelial cell count (ECC) and endothelial cell loss (ECL) were analyzed; (3) Results: The half time of the ECD was 3.03 months for the early phase and 131.50 months for the late phase. The predicted time-lapse interval to reach 500 cells/mm2 was 218 months (18.17 years), while the time-lapse interval to reach 250 cells/mm2 was 349 months (29.08 years). There was no statistically significant difference between the ECL in DMEK combined with cataract extraction and DMEK alone at 24 months (p ≥ 0.20). At the late phase, long-term ECL prediction revealed a lower ECC half time in patients undergoing DMEK combined with cataract surgery (98.05 months) than DMEK alone (250.32 months); (4) Conclusions: Based on the mathematical modeling, a predicted average half-life of a DMEK graft could reach 18 years in FECD. Moreover, combining cataract extraction with DMEK could result in excessive ECL in the long term.

The Impact of Vaping on the Ocular Surface: A Systematic Review of the Literature.

Background: The use of electronic cigarettes has become increasingly popular in recent years. However, the impact that electronic cigarettes have on the ocular surface is not well known. Therefore, the aim of this review is to explore the current literature on the acute and chronic sequelae of electronic cigarettes on the ocular surface. Methods: A systematic review of the literature was undertaken by keyword searching on the Embase, Medline, and Web of Science databases. Articles identified through the search underwent title/abstract screening, full-text screening, and data extraction. Results: A total of 18 studies were included in this review. Non-intended ocular surface exposures and intended exposures on the ocular surface were found to be associated with the use of electronic cigarettes. Conclusions: The impact of vaping on the ocular surface is not benign. There are significant risks that vaping can pose to the ocular surface. Hence, it is necessary to develop appropriate risk communication tools given the increasing popularity of this activity. Additionally, future long-term studies are needed to better understand the long-term impacts of vaping on the ocular surface given the lack of current data.

Trends and Clinical Outcomes of Fungal Keratitis in Canada: A 20-year Retrospective Multicentre Study.

PURPOSE: An increase in fungal and particularly filamentous keratitis has been observed in many geographic areas, mostly in contact lens wearers. This study seeks to characterize long-term trends in fungal keratitis in a continental climate area to provide guidance for diagnosis and treatment. DESIGN: Retrospective multicentric case series. METHODS: Cases of microbiology-confirmed fungal keratitis from 2003 to 2022 presenting to tertiary care centers across Canada were included. Charts were reviewed for patient demographics, risk factors, visual acuity, and treatments undertaken. RESULTS: A total of 138 patients were identified: 75 had yeast keratitis while 63 had filamentous keratitis. Patients with yeast keratitis had more ocular surface disease (79% vs 28%) while patients with filamentous keratitis wore more refractive contact lenses (78% vs 19%). Candida species accounted for 96% of all yeast identified, while Aspergillus (32%) and Fusarium (26%) were the most common filamentous fungi species. The mean duration of treatment was 81 ± 96 days. Patients with yeast keratitis did not have significantly improved visual acuity with medical treatment (1.8 ± 1 LogMAR to 1.9 ± 1.5 LogMAR, P = .9980), in contrast to patients with filamentous keratitis (1.4 ± 1.2 LogMAR to 1.1 ± 1.3 LogMAR, P = .0093). CONCLUSIONS: Fungal keratitis is increasing in incidence, with contact lenses emerging as one of the leading risk factors. Significant differences in the risk factors and visual outcomes exist between yeast keratitis and filamentous keratitis which may guide diagnosis and treatment.

A novel rat contact lens model for Fusarium keratitis.

PURPOSE: The aim of this study was to develop and characterize a new contact lens-associated fungal keratitis rat model and to assess the ability of non-invasive spectral-domain optical coherence tomography (SD-OCT) to detect pathological changes in vivo in fungal keratitis. METHODS: We used SD-OCT to image and measure the cornea of Sprague Dawley rats. Fusarium infection was initiated in the rat eye by fitting Fusarium solani-soaked contact lenses on the experimental eye, while the control animals received contact lenses soaked in sterile saline. The fungal infection was monitored with periodic slit-lamp examination and in vivo SD-OCT imaging of the rat eye, and confirmed by histology, counting of viable fungi in the infected rat cornea, and PCR with specific primers for Fusarium sp. RESULTS: We imaged and measured the rat cornea with SD-OCT. Custom-made contact lenses were developed based on the OCT measurements. Incubation of contact lenses in a F. solani suspension resulted in biofilm formation. We induced contact lens-associated Fusarium keratitis by fitting the rat eyes for 4 h with the Fusarium-contaminated contact lenses. The SD-OCT images of the cornea correlated well with the slit-lamp and histopathological results and clearly defined clinical signs of infection, namely, increased corneal thickening, loss of epithelial continuity, hyper-reflective areas representing infiltrates, and endothelial plaques characteristic of fungal infection. Moreover, in three cases, SD-OCT detected the infection without any clear findings on slit-lamp examination. Infection was confirmed with histological fungal staining, PCR, and microbiological culture positivity. CONCLUSIONS: We developed a highly reproducible rat contact lens model and successfully induced contact lens-associated Fusarium keratitis in this model. The clinical presentation of contact lens-associated Fusarium keratitis in the rat model is similar to the human condition. SD-OCT is a valuable tool that non-invasively revealed characteristic signs of the fungal infection and could provide sensitive, objective monitoring in fungal keratitis.

Peripheral hypertrophic subepithelial corneal degeneration: nomenclature, phenotypes, and long-term outcomes.

PURPOSE: To describe the long-term outcomes of peripheral hypertrophic subepithelial corneal degeneration. DESIGN: Retrospective case series. PARTICIPANTS: Twenty-two patients under the care of the External Disease Service, Moorfields Eye Hospital. METHODS: All patients matching clinical diagnostic criteria were included. Symptomatic patients were managed either conservatively or were offered superficial keratectomy in progressive cases where symptom control was inadequate. All excised tissue was examined histologically. MAIN OUTCOME MEASURES: Clinical phenotype, symptoms, recurrence rate after surgery, and histopathologic results. RESULTS: Twenty-two white patients (20 women and 2 men; age range, 27-88 years; median age, 42 years) had peripheral, usually bilateral (20/22 [91%]), elevated circumferential peripheral subepithelial corneal opacities and adjacent abnormal limbal vasculature, with or without pseudopterygia in 9 patients (41%), among whom 7 (32%) patients had bilateral disease. Apart from the abnormal vasculature, there were no signs of chronic ocular surface inflammation. Symptoms were ocular surface discomfort in 10 patients (45%), reduced vision in 4 patients (18%), and both of these in 5 patients (23%). Three patients (14%) were asymptomatic. There was no treatment in 6 patients (27%), topical lubricants in 8 patients (36%), spectacles in 1 patient (5%), and superficial keratectomy in 7 patients (32%; 5 bilateral), which was repeated for incomplete primary excision in 1 eye of 2 patients (9%) and for a bilateral recurrence in 1 patient (5%). Median follow-up after excision was 5 years (range, 1-11 years). Histopathologic changes were similar to those observed in pterygia (vascular component) and Salzmann's nodular degeneration (corneal component). CONCLUSIONS: Peripheral hypertrophic subepithelial corneal degeneration is an uncommon, usually bilateral, idiopathic disorder, occurring mostly in white women with a distinct phenotype. The condition was first described in 2003. Further cases among some patients have been described in more recent case series of Salzmann's nodular degeneration and diffuse keratoconjunctival proliferation, as well as in the previously described familial pterygoid corneal degeneration. Surgical excision was required in 30% of patients in this series, with infrequent short-term recurrences. The cause is uncertain. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Outcomes of XEN Stent in Patients With Glaucoma and Previous Corneal Transplantation.

PRCIS: The XEN stent safely and effectively controls intraocular pressure in select patients with history of corneal transplantation. PURPOSE: Glaucoma is a common complication after corneal transplantation and can be difficult to manage in these patients. This study reports outcomes of XEN stent implantation in eyes with glaucoma in the setting of previous corneal transplantation. PATIENTS AND METHODS: Noncomparative retrospective case series including eyes with a history of corneal transplantation and subsequent XEN stent implantation by a single glaucoma surgeon in Surrey, British Columbia, between 2017 and 2022. The analysis included patient demographics, pre and postoperative intraocular pressure (IOP), pre and postoperative glaucoma medications, peri and postoperative complications and interventions, and incidence of repeat corneal transplantation and additional glaucoma procedures to control IOP. RESULTS: Fourteen eyes with previous cornea transplantation underwent XEN stent implantation. Mean age was 70.1 years (range: 47-85 y). Mean follow-up was 18.2 months (range: 1.5-52 mo). The most common glaucoma diagnosis was secondary open angle glaucoma (50.0%). There was a significant reduction in IOP and the number of glaucoma agents at all postoperative time points ( P < 0.05). IOP decreased from 32.7 ± 10.0 mm Hg at baseline to 12.5 ± 4.7 mm Hg at the most recent follow-up. Glaucoma agents decreased from 4.0 ± 0.7 to 0.4 ± 1.0. Two eyes required additional glaucoma surgery to control IOP, with an average time to reoperation of 7 weeks. Two eyes underwent repeat corneal transplantation, with an average time to reoperation of 23.5 months. CONCLUSIONS: In selected patients with previous corneal transplants and refractory glaucoma, the XEN stent was safely implanted and effectively reduced IOP in the short term.

Pathophysiology of Corneal Endothelial Cell Loss in Dry Eye Disease and Other Inflammatory Ocular Disorders.

PURPOSE: Dry eye disease (DED) and other inflammatory ocular disorders have been reported to be associated with decreased corneal endothelial cell density (CECD), however the mechanism of underlying endothelial cell loss remains unknown. METHODS: We conducted a comprehensive literature search of English-written publications on dry eye disease, corneal endothelial cell loss, Sjögren's syndrome, and Graft Vs Host Disease (GVHD), to review the effects of DED and other inflammatory ocular surface conditions on CECD. RESULTS: A total of 78 studies were included in our study. Loss of corneal neurotrophic support, cytotoxic stress, and a heightened immune response, all of which may occur secondarily to a common causative agent such as inflammation, are major contributors to reduced CECD. CONCLUSION: More studies are needed to determine how the interrelated pathways of altered corneal nerve function and upregulated expression of inflammatory activity influence corneal endothelial cell loss.

Global impact of COVID-19 on corneal donor tissue harvesting and corneal transplantation.

Introduction: The purpose of this review is to consolidate and examine the available literature on the coronavirus disease 2019 pandemic and its effect on corneal transplantation and eye banking. Methods: A primary literature search was conducted using the PubMed (Medline) database with keywords and MeSH terms such as "corneal transplantation," "eye banks," "keratoplasty" and then were combined with COVID-19. Relevant articles through September 2022 were assessed and 25 articles were included in this review. Results: Donor tissue volumes declined globally during lockdown periods due to a lower number of referrals and tighter tissue screening guidelines. Rates of elective surgeries decreased in the lockdown period compared to respective periods in previous years. However, changes in rates of emergency procedures were not uniform across different regions. Moreover, rates of different elective corneal grafts [i.e., penetrating keratoplasty (PK), endothelial keratoplasty (EK), or anterior lamellar keratoplasty (ALK)] were affected differently with the pattern of change being dependent on region-specific factors. Conclusion: Both donor tissue volumes and rates of corneal transplant procedures were affected by lockdown restrictions. The underlying etiology of these changes differed by region. Examining the range of impact across many countries as well as the contributing factors involved will provide guidance for future global pandemics.

Visual Outcomes of Cataract Surgery in Patients With Keratoconus Using Toric and Non-toric Lenses.

PURPOSE: To compare the accuracy and outcomes of different intraocular lens (IOL) power calculation formulas in eyes with keratoconus undergoing cataract surgery with toric and non-toric IOLs. METHODS: This was a consecutive retrospective case series study including patients from the Cornea Service at the Department of Ophthalmology and Visual Sciences at the University of British Columbia, Vancouver, Canada, from 2000 to 2020. Keratoconus was diagnosed based on corneal topography and clinician opinion. Patients who underwent topography-guided photorefractive keratectomy, intracorneal ring segments implantation, or corneal transplant were excluded. The manifest spherical equivalent, prediction errors, and median absolute errors were calculated. Descriptive statistics were expressed as mean ± standard deviation. RESULTS: There were 160 eyes from 101 patients; 136 eyes received non-toric lenses and 24 eyes received toric lenses. Most patients had mild disease (< 48.00 diopters [D]) when stratified by steep keratometry values. Patients with severe disease (> 53.00 D) were significantly more hyperopic following surgery (P < .05). The Barrett Universal II (0.26 D, inter-quartile range [IQR] = 0.4), Holladay 2 (0.31, IQR = 1.2), and SRK/T (0.42, IQR = 0.86) formulas had the lowest median absolute error. The postoperative prediction error following toric lens insertion was not significantly different than following non-toric lens insertion, and the mean absolute astigmatism was significantly reduced with toric lenses. CONCLUSIONS: The Barrett Universal II, Holladay 2, and SRK/T were the most accurate IOL power calculation formulas in patients with keratoconus undergoing cataract surgery. Hyperopic surprise was increased in severe keratoconus. Toric IOLs may be considered in patients with mild keratoconus. [J Refract Surg. 2023;39(5):319-325.].