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 = 0.9980), in contrast to patients with filamentous keratitis (1.4 ± 1.2 LogMAR to 1.1 ± 1.3 LogMAR, p = 0.0093). 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.

Incidence of ocular surface squamous neoplasia in pterygium specimens.

OBJECTIVE: Pterygium and ocular surface squamous neoplasia (OSSN) have been recognized as likely related conditions and share similar risk factors such as ultraviolet radiation and chronic inflammation. The purpose of this study is to review the incidence of OSSN in pathology specimens sent as pterygium at a single tertiary centre between 2010 and 2022. METHODS: This is a retrospective chart review of patients operated on for pterygium between 2010 and 2022 at the University of Montreal Health Centre. Data collected include baseline demographics, results of pathology specimen, and clinical information for cases diagnosed as OSSN on pathology. RESULTS: A total of 1559 patients were operated on for a clinical diagnosis of pterygium between 2010 and 2022, of which 854 patients (55%) were male. A total of 1142 specimens had available pathology reports, and most of the specimens were consistent with pterygium on pathology (1105 of 1142; 97%). There was an unexpected finding of 3 cases of OSSN (3 of 1142; 0.3%). Other diagnosis besides pterygium were seen in 3% of specimens (34 of 1142), including nevus (n = 12), spheroidal degeneration (n = 3), pyogenic granuloma (n = 3), and lymphangiectasia (n = 2). The 3 cases of OSSN included an 81-year-old male of French-Canadian background, a 52-year-old male of South Asian background, and a 59-year-old female of French-Canadian background. The pathology was diagnosed as conjunctival intraepithelial neoplasia (CIN) grade 3, CIN grade 2, and CIN grade 2, respectively. CONCLUSION: The finding of OSSN in pterygium is rare in our population but can be clinically difficult to distinguish. It is important to send all pterygium specimens for pathology.

Survey: Preferred practice patterns in the diagnosis of mucous membrane pemphigoid amongst cornea specialists.

PURPOSE: To evaluate preferred diagnostic tools and treatment decision-making factors in cases suspicious of mucous membrane pemphigoid (MMP) amongst ophthalmologists and cornea specialists. METHODS: Web-based survey, consisting of 14 multiple choice questions, posted to the Cornea Society Listserv Keranet, the Canadian Ophthalmological Society Cornea Listserv, and the Bowman Club Listserv. RESULTS: One hundred and thirty-eight ophthalmologists participated in the survey. Eighty-six percent (86%) of respondents were cornea trained and practiced in either North America or Europe (83%). Most respondents (72%) routinely perform conjunctival biopsies for all suspicious cases of MMP. For those who do not, fear that biopsy will exacerbate inflammation was the most common reason to defer investigation (47%). Seventy-one percent (71%) performed biopsies from perilesional sites. Ninety-seven percent (97%) ask for direct (DIF) studies and 60% for histopathology in formalin. Most do not recommend biopsy at other non-ocular sites (75%), nor do they perform indirect immunofluorescence for serum autoantibodies (68%). Immune-modulatory therapy is started following positive biopsy results for most (66%), albeit most (62%) would not let a negative DIF influence the choice of starting treatment should there be clinical suspicion of MMP. Differences in practice patterns as they relate to level of experience and geographical location are contrasted to the most up-to-date available guidelines. CONCLUSION: Responses to the survey suggest that there is heterogeneity in certain practice patterns for MMP. Biopsy remains an area of controversy in dictating treatment plans. Identified areas of need should be targeted in future research.

Review of clinical trials addressing the Boston Keratoprosthesis.

OBJECTIVE: The Boston Keratoprosthesis (KPro) has gained recognition as an alternative for patients with severe corneal disease and a poor probability of success with traditional penetrating keratoplasty. This review summarizes the knowledge clinical trials have brought to KPro and discusses ongoing trials. DESIGN: Systematic review. METHODS: A literature review across PubMed, Ovid MEDLINE, Cochrane CENTRAL, and ClinicalTrials.gov was performed to identify relevant published clinical trials reporting on the KPro from all years up until September 2021. All published trials were included. RESULTS: There are 6 published and 6 ongoing clinical trials studying the Boston KPro. The number of patients included per trial ranged from 8 to 37. The average age of patients included per trial ranged from 39 to 62 years. Patients were followed for an average of 36.3 ± 41.8 months. Fifty percent (3 of 6) of KPro clinical trials were randomized. Indication for KPro was reported in 67% of trials (4 of 6), with primary KPro accounting for 22% of unique eyes (13 of 58) and KPro after corneal graft failure accounting for 41% of unique eyes (24 of 58), when reported. Using version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2) to assess quality and risk of bias, 50% of trials (3 of 6) had a low risk of bias, 33% (2 of 6) had some bias concerns, and 17% (1 of 6) had a high risk of bias. CONCLUSIONS: There are few clinical trials published and underway on the Boston KPro, and none directly compare KPro outcomes with repeat corneal transplantation. There is a need for long-term clinical trials on the KPro to provide quality evidence for clinical decision making.

Probing mechanisms and improving management of glaucoma following Boston keratoprosthesis surgery.

Corneal blindness is a leading cause of visual impairment worldwide. The most common treatment is to replace the diseased cornea with standard corneal transplantation. In eyes at high risk of graft failure, the Boston keratoprosthesis type 1 (KPro) can be used to restore vision and is currently the most frequently used artificial cornea in the world. However, glaucoma is a well-known complication of KPro surgery and is the most important threat to vision in KPro-implanted eyes. This chronic disease is influenced by elevated intraocular pressure (IOP) and damages the optic nerve, leading to progressive vision loss. In KPro patients, glaucoma is highly prevalent and extremely challenging to manage, yet its exact cause remains unknown.

Success of the Canadian Ophthalmological Society's first virtual meeting amid COVID-19 pandemic.

OBJECTIVE: To assess participant attendance and engagement for an in-person Canadian Ophthalmological Society (COS) annual meeting (2019) compared with a virtual COS annual meeting (2020). DESIGN: Retrospective case-control study of key event metrics of the 2019 and 2020 COS meetings as well as Twitter activity. METHODS: Key annual meeting metrics were collected retrospectively for 2020 virtual meeting and compared with the most recent in-person annual meeting cohort from 2019. Metrics collected included attendance by ophthalmology specialist, geographic distribution of attendees, postevent survey rate, and social media engagement (Twitter). RESULTS: Overall, there was a 7% (n = 60) increase in the number of registrants between 2019 and 2020. The largest change noted was the increase in registrants from British Columbia (n = 78). More ophthalmologists registered for the 2020 meeting than for 2019 meeting (627 versus 592). Of those who registered for the meeting, meeting participation (defined as checking in for the 2019 and logging in for the 2020 meetings) increased from 70% in 2019 to 79% in 2020. There was a 158% (n = 15 000) increase in tweet impressions in 2020 compared with 2019. CONCLUSION: The first COS virtual meeting attracted more participants and was available to a geographically wider audience. Indeed, more professionals from provinces that are geographically further from the traditional COS meeting locations were able to participate in the event. Meeting engagement on a social media platform increased in the virtual meeting in 2020 relative to the in-person meeting in 2019, and possible enablers for increased engagement should be sought and incorporated into future meetings.

Boston type I keratoprosthesis versus penetrating keratoplasty following a single failed corneal graft.

BACKGROUND/OBJECTIVES: To compare long-term outcomes of the Boston type 1 keratoprosthesis (KPro) with penetrating keratoplasty (PKP) in patients with a failed first PKP. SUBJECTS/METHODS: In this retrospective comparative case series, 48 eyes of 48 patients who underwent a second corneal replacement procedure after a first failed PKP at the Centre Hospitalier de l'Université de Montréal from 2008 to 2020 were included. Minimum follow-up duration was 5 years, and patients with keratoconus were excluded since such subjects are not candidates for KPro. Main outcome measures included best-corrected visual acuity (BCVA), postoperative complications, graft survival and subsequent interventions. RESULTS: Mean follow-up was 6.4 years for PKP and 9.6 years for KPro (p < 0.001). Preoperative BCVA was better in PKP patients (means 1.67 vs 2.13, p = 0.041). Visual outcomes were similar between groups. KPro patients developed 0.263 complication per patient-year (ppy) compared to 0.245 ppy or PKP. The most common complications for PKP were corneal complications (0.088 ppy) and glaucoma worsening (0.041 ppy). In KPro, glaucoma worsening (0.046 ppy), vitreoretinal complications (0.042 ppy) and retroprosthetic membrane (0.042 ppy) were the most frequent. Graft failure (69.6 vs 20.0%, p < 0.001) and reoperation rates (56.5 vs 12.0%, p = 0.001) were significantly higher for PKP. Failure mainly resulted from decompensation or rejection in PKP, while all five failures in KPro were caused by melt and/or extrusion. CONCLUSIONS: Both interventions showed similar visual outcomes. Complication profiles were different, with more posterior segment complications in the KPro group, and more corneal complications in the PKP group, often necessitating regraft.

Probing mechanisms and improving management of glaucoma following Boston keratoprosthesis surgery.

ENGLISH SUMMARY: Corneal blindness is a leading cause of visual impairment worldwide. The most common treatment is to replace the diseased cornea by standard corneal transplantation. In eyes at high risk of graft failure, the Boston keratoprosthesis type 1 (KPro) can be used to restore vision and is currently the most frequently used artificial cornea in the world. However, glaucoma is a well-known complication of KPro surgery and is the most important threat to vision in KPro-implanted eyes (paper I). This chronic disease is influenced by elevated intraocular pressure (IOP) and damages the optic nerve, leading to progressive vision loss. In KPro patients, glaucoma is highly prevalent and extremely challenging to manage, yet its exact cause remains unknown. The overall purpose of this PhD Thesis (Geoffrion, 2021) was to better understand the mechanisms and how to improve management of glaucoma after KPro implantation. The approaches used in this thesis included investigating one of the largest KPro patient cohorts in North America, with a total of 157 operated patients at that time, as well as studying KPro surgery and outcomes in mice. The first objective was to identify risk factors for glaucoma development and progression after KPro implantation (paper II). Multivariate logistic regression revealed that high preoperative IOP signals a higher risk for both glaucoma development and progression. Stromal and endothelial corneal disorders were less associated with glaucoma progression, while autoimmune and ocular surface diseases precipitated glaucoma development. Second, there is no objective evidence that indicates the best order for glaucoma surgeries and KPro implantation. By comparing medical and surgical management in KPro eyes with either preexisting or de novo glaucoma (paper III), we showed that glaucoma surgery may be performed before or at the time of KPro in eyes with preexisting glaucoma to limit progression without increasing complications. In eyes with de novo glaucoma, glaucoma surgery did not increase complications compared with medications. Third, among glaucoma surgery interventions, the two most frequently implanted glaucoma drainage devices were compared in KPro patients (paper IV). Compared with the Ahmed glaucoma valve, the Baerveldt glaucoma implant was associated with lower failure rates, without increased postoperative complications. Fourth, even with aggressive management, many KPro patients suffer from progressive optic nerve damage, sometimes despite normal IOP. Inflammatory cytokines play an important role in glaucomatous optic neuropathy, but their role in KPro-associated glaucoma is still unknown. By analysing tear fluid of KPro patients by multiplex bead immunoassay (paper V), we identified that cytokines TNF-a, IL-1b, FGF-basic and IFN-g were elevated in KPro patients with glaucoma compared to those without. These cytokines correlated with optic nerve excavation and IOP. For the first time in humans, these results concorded with the elevations of TNF-a and IL-1b documented in the mouse KPro model. Ocular surface inflammation may thus reflect the inflammatory processes that perpetuate glaucoma damage years after KPro surgery. Fifth, we determined that miniaturized mouse KPro implantation requires extensive practice to be used as a reproducible model of glaucoma post-KPro (paper VI). KPro animal models with larger eyes and a full-thickness, 360-degree corneal excision should be prioritized to best validate human outcomes. In conclusion, glaucoma in KPro eyes is a long-lasting and multifactorial process. Most probable mechanisms combine IOP-independent inflammation mediated by TNF-a and IL-1b that prolong glaucoma damage, together with post-surgical angle closure elevating the IOP. Altogether, our results inform glaucoma risk profiling of transplant recipients, improvement of surgical management of KPro patients with glaucoma and development of targeted treatments to minimize glaucomatous damage after KPro. Ultimately, this work has the potential to preserve the vision of thousands of patients who undergo KPro surgery every year worldwide and to provide insight for the role of inflammation in other diseases involving neuronal damage. RÉSUMÉ (FRENCH SUMMARY): La cécité cornéenne est l'une des causes les plus importantes de déficience visuelle dans le monde. Le traitement usuel est de remplacer la cornée malade par une greffe de cornée traditionnelle. Dans les yeux à haut risque d'échec de greffe, la kératoprothèse de Boston de type 1 (KPro) peut rétablir la vision et est la cornée artificielle la plus utilisée au monde. Cependant, le glaucome est une complication importante de la KPro (papier I). Cette maladie chronique est influencée par une pression intraoculaire (PIO) élevée et endommage le nerf optique, menant à une perte de vision. Chez les patients avec KPro, le glaucome est fréquent et difficile à contrôler, mais sa cause exacte demeure inconnue. L'objectif principal de cette thèse est de découvrir les mécanismes et d'optimiser la prise en charge du glaucome après l'implantation de la KPro. Pour ce faire, nous avons investigué l'une des plus grandes cohortes de patients KPro en Amérique du Nord avec un total de 157 patients, ainsi qu'un groupe de souris ayant reçu une implantation de kératoprothèse. Le premier but était d'identifier les facteurs de risque pour le développement et la progression du glaucome après la KPro (papier II). Par régression logistique multivariée, nous avons démontré qu'une PIO préopératoire élevée mène à un plus grand risque de développement et de progression du glaucome. Les maladies cornéennes stromales ou endothéliales sont moins associées à une progression, alors que les maladies autoimmunes ou de la surface oculaire précipitent le développement du glaucome. Deuxièmement, il n'existe aucune donnée objective pour indiquer le meilleur ordre des chirurgies de glaucome et de KPro. En comparant les traitements médicaux et chirurgicaux des yeux KPro avec glaucome (papier III), nous avons démontré que les chirurgies de glaucome peuvent limiter la progression en étant effectuées avant ou pendant l'implantation de KPro dans les yeux avec glaucome préexistant, sans augmenter les complications. Dans le glaucome de novo, les chirurgies de glaucome n'augmentent pas les complications en comparaison aux médicaments. Troisièmement, les deux implants de glaucome les plus communs ont été étudiés chez les patients KPro (papier IV). Comparé à la valve Ahmed, l'implant Baerveldt est associé à des taux d'échec plus bas, sans augmentation des complications. Quatrièmement, même avec une prise en charge agressive, plusieurs patients KPro souffrent de glaucome qui progresse, parfois sans PIO élevée. Les cytokines inflammatoires jouent un rôle dans la pathophysiologie du glaucome, mais leur rôle dans le glaucome associé à la KPro est inconnu. En analysant les larmes de patients KPro (papier V), nous avons identifié que les cytokines TNF-a, IL-1b, FGF-basic et IFN-g sont élevées chez les patients KPro avec glaucome comparé à ceux sans glaucome. Ces cytokines corrèlent avec l'excavation du nerf optique et la PIO. Pour la première fois chez les humains, ces résultats concordent avec les niveaux élevés de TNF-a et IL-1b documentés dans le modèle murin de KPro. L'inflammation de la surface oculaire pourrait donc refléter les processus inflammatoires qui perpétuent le dommage glaucomateux. Cinquièmement, nous avons déterminé que l'implantation de la KPro miniature chez la souris requiert beaucoup de pratique pour être utilisé comme modèle de glaucome post-KPro (papier VI). Des modèles animaux avec des yeux plus larges et une excision cornéenne de pleine épaisseur sur 360 degrés devraient être priorisés pour valider les résultats chez l'humain. En conclusion, le glaucome associé à la KPro est un processus multifactoriel qui persiste à long terme. Les mécanismes probables combinent l'inflammation médiée par TNF-a et IL-1b et une fermeture de l'angle qui augmente la PIO. Nos résultats contribuent à établir les facteurs de risque de glaucome pour les receveurs de KPro, à améliorer leur prise en charge et à développer des thérapies ciblées. Ce travail a le potentiel de préserver la vision de milliers de patients recevant une KPro chaque année dans le monde et d'aider à mieux comprendre le rôle de l'inflammation dans d'autres maladies avec atteinte neuronale.

Hypo-osmolar accelerated corneal crosslinking on resultant sub-400 µm topography-guided excimer regularized keratoconus corneas.

PURPOSE: To investigate the efficacy and safety of phototherapeutic keratectomy (PTK) with topography-guided photorefractive keratectomy (T-PRK) corneal regularization followed by sequential hypo-osmolar riboflavin accelerated corneal crosslinking (CXL) in keratoconic (KC) eyes with <400 µm stromal bed thickness after excimer ablation. SETTING: Multisurgeon multicenter standardized protocol practice. DESIGN: Retrospective multicenter case series. METHODS: This study included progressive KC eyes that underwent PTK and T-PRK combined with accelerated CXL and had a corneal stromal bed thickness of <400 µm after excimer ablation before administration of hypo-osmolar riboflavin. Demographics and clinical measures were reviewed at baseline and every follow-up visit. RESULTS: 61 consecutive eyes had a mean corneal stromal bed thickness of 367 ± 21 µm after excimer laser normalization. Postoperatively, uncorrected distance visual acuity (UDVA) improved by 0.29 logMAR ( P < .0001), corrected distance visual acuity (CDVA) improved by 0.07 logMAR ( P = .0012), and maximum keratometry (Kmax) decreased by 4.67 diopters ( P < .0001). The safety index was favorable (1.29 ± 0.56), with stable manifest astigmatism, Kmax, and pachymetry at 12 months. 2 eyes (3%) showed evidence of keratometric progression on topography. CONCLUSIONS: In KC corneas thinner than 400 µm after excimer ablation, PTK epithelial removal followed by T-PRK and hypo-osmolar accelerated CXL decreases manifest astigmatism and Kmax, improves UDVA and CDVA, and halted disease progression in 97% of eyes at 12 months. These outcomes are comparable with thicker ablated corneas not requiring hypo-osmolar stromal swelling.

The treatment of end-stage corneal disease: penetrating keratoplasty compared with Boston type 1 keratoprosthesis.

Penetrating keratoplasty (PKP) yields excellent results for restoring vision in end-stage corneal diseases. However, its success is limited to high-risk diseases such as aniridia, chemical burns, autoimmune corneal diseases, and herpetic eye disease. Boston type 1 keratoprosthesis (BKPro) offers another option to these patients. Since 1992, improvements in perioperative management and device construction have significantly increased the use of BKPro worldwide and challenged the therapeutic role of PKP in these patients. This review aims to evaluate BKPro's place in the treatment algorithm of these high-risk patients to assist surgeons' decision-making. PKP and BKPro are compared in three outcome categories: visual acuity, graft retention and failure, and complications profile. Special attention is given to comparing secondary BKPro versus repeated PKP as well as primary BKPro versus primary PKP. We conclude that secondary BKPro bears a better prognosis than repeated PKP in most high-risk patients. Similarly, primary BKPro likely confers improved outcomes over primary PKP in most high-risk recipients. However, current evidence is based on retrospective designs, and controlled prospective randomized trials are required to validate these conclusions.

Idiopathic Vitritis after Boston Type 1 Keratoprosthesis Implantation: Incidence, Risk Factors and Outcomes in a Multicentric Cohort.

PURPOSE: To determine incidence, risks factors for, and outcomes of idiopathic vitritis (IV) after Boston type 1 keratoprosthesis (KPro) implantation. METHODS: Retrospective, consecutive case series. Risk factors were analyzed between IV group and No IV group. RESULTS: IV occurred in 32/350 procedures (9.1%), for an average incidence of 0.02 cases per procedure-year. Presumed infectious keratitis was the only risk factor identified (HR = 7.65) Corneal necrosis and retinal detachment occurred significantly more frequently in IV group (all P < .05). By last follow-up, the cumulative proportion of eyes that maintained a visual acuity >20/200 was significantly lower in IV group (P = .01), as was the KPro retention rate (HR = 0.26). CONCLUSIONS: IV is associated with infectious keratitis, indicating that the vitritis may not be a sterile process. The increased incidence of subsequent complications leads to significantly decreased visual acuity and KPro retention in affected eyes.