Predictive factors of graft detachment and rebubbling after descemet membrane endothelial keratoplasty.

PURPOSE: To identify risk and predictive factors associated with the need of rebubbling in the eye of patients who underwent a descemet membrane endothelial keratoplasty (DMEK). METHODS: The records of patients who underwent DMEK were retrospectively analyzed. Data regarding comorbidities, intraoperative characteristics, and postoperative treatments or complications were collected. The central corneal thickness (CCT) was measured by optical coherence tomography before and the day after DMEK. Univariate and multivariate analyses were performed. RESULTS: Of the 333 DMEK, rebubbling was performed in 119 cases (36%). Preoperative subepithelial fibrosis and a history of penetrating keratoplasty (PK) were associated with significantly more graft detachment [OR of 3.55 (2.02-6.32; P < 0.001) and 5.89 (2.00-21.86; P = 0.003), respectively]. A decreased CCT the day after surgery reduced by 5.7-fold the risk of rebubbling (sensitivity/specificity of 0.42/0.93). Conversely, a 20% increase in the CCT the day after surgery increased by 4.5-fold the risk of rebubbling (sensitivity/specificity of 0.42/0.91). CONCLUSION: Variation of the CCT could be used as a predictive factor of rebubbling after DMEK. Patients with a 20% increase of CCT the day after surgery are at higher risk of graft detachment. Conversely, a reduced CCT the day after the surgery is associated with a reduced risk of rebubbling. Subepithelial fibrosis and history of PK were also identified as risk factors for rebubbling. Those predictive factors may help develop a customized approach for patients undergoing DMEK surgery.

Alleviation of Endoplasmic Reticulum Stress Enhances Human Corneal Epithelial Cell Viability under Hyperosmotic Conditions.

Tear hyperosmolarity plays an essential role in the initiation and progression of dry-eye disease. Under a hyperosmotic environment, corneal epithelial cells experience perturbations in endoplasmic reticulum function that can lead to proinflammatory signaling and apoptosis. In this study, we investigated the effect of tauroursodeoxycholic acid (TUDCA), a chemical chaperone known to protect against endoplasmic reticulum stress, on corneal epithelial cells exposed to hyperosmotic conditions. We found that the expression of the genes involved in the activation of the unfolded protein response and the pro-apoptotic transcription factor DDIT3 were markedly upregulated in patients with Sjögren's dry-eye disease and in a human model of corneal epithelial differentiation following treatment with hyperosmotic saline. Experiments in vitro demonstrated that TUDCA prevented hyperosmotically induced cell death by reducing nuclear DNA fragmentation and caspase-3 activation. TUDCA supplementation also led to the transcriptional repression of CXCL8 and IL5, two inflammatory mediators associated with dry-eye pathogenesis. These studies highlight the role of hyperosmotic conditions in promoting endoplasmic reticulum stress in the cornea and identify TUDCA as a potential therapeutic agent for the treatment of dry-eye disease.

Peripheral ulcerative keratitis in rheumatoid arthritis patients taking tocilizumab: paradoxical manifestation or insufficient efficacy?

OBJECTIVES: Peripheral ulcerative keratitis (PUK) is a severe corneal condition associated with uncontrolled RA. Tocilizumab (TCZ) is used to control RA, however, episodes of paradoxical ocular inflammation have been reported in TCZ-treated patients. We report a case series of PUK in TCZ-treated RA patients with ophthalmological and systemic findings and discuss the potential underlying mechanisms. METHODS: Four patients (six eyes), 47-62 years of age, were included. At the onset of PUK, the median duration of RA was 13 years [interquartile range (IQR) 3-13] and the median treatment with TCZ was 9 months (IQR 3-14). Two patients had active disease [28-joint DAS (DAS28) >3.2] and the disease was controlled in two patients (DAS28 ≤3.2). RESULTS: TCZ was initially replaced by another immunomodulatory treatment in all patients and later reintroduced in two patients without PUK recurrence. Corneal inflammation was controlled in all cases with local and systemic treatments, with severe visual loss in one eye. CONCLUSION: PUK may occur in patients with long-standing RA after a switch to TCZ and can be interpreted, depending on the context, as insufficient efficacy or a paradoxical manifestation. These cases highlight the urgent need for reliable biomarkers of the efficacy and paradoxical reactions of biologics.

P63-related disorders: Dermatological characteristics in 22 patients.

In P63-related ectodermal dysplasias (ED), the clinical characteristics focus on extra-cutaneous manifestations. The dermatological phenotype remains incompletely characterized. We report the dermatological features of 22 patients carrying a TP63 mutation. Erosions, erythroderma and pigmentary anomalies are characteristics of P63-related ED. Our data suggest that patients might be classified into two major P63-related disorders: AEC and EEC. RHS and ADULT represent mild AEC and EEC forms, respectively.

Ocular adverse events associated with antibody-drug conjugates used in cancer: Focus on pathophysiology and management strategies.

Antibody-drug conjugates (ADCs) are designed to maximize cancer cell death with lower cytotoxicity toward noncancerous cells and are an increasingly valuable option for targeted cancer therapies. However, anticancer treatment with ADCs may be associated with ocular adverse events (AEs) such as dry eye, conjunctivitis, photophobia, blurred vision, and corneal abnormalities. While the pathophysiology of ADC-related ocular AEs has not been fully elucidated, most ocular AEs are attributed to off-target effects. Product labelling for approved ADCs includes drug-specific guidance for dose modification and management of ocular AEs; however, limited data are available regarding effective strategies to minimize and mitigate ocular AEs. Overall, the majority of ocular AEs are reversible through dose modification or supportive care. Eye care providers play key roles in monitoring patients receiving ADC therapy for ocular signs and symptoms to allow for the early detection of ADC-related ocular AEs and to ensure the timely administration of appropriate treatment. Therefore, awareness is needed to help ophthalmologists to identify treatment-related ocular AEs and provide effective management in collaboration with oncologists as part of the patient's cancer care team. This review provides an overview of ocular AEs that may occur with approved and investigational ADC anticancer treatments, including potential underlying mechanisms for ADC-related ocular AEs. It also discusses clinical management practices relevant to ophthalmologists for prevention, monitoring, and management of ADC-related ocular AEs. In collaboration with oncologists, ophthalmologists play a vital role in caring for patients with cancer by assisting with the prompt recognition, mitigation, and management of treatment-related ocular AEs.

Immediate and Delayed Effects of Punctal Plug Insertion on Tear Meniscus Height in Severe Aqueous-Deficient Dry Eye.

PURPOSE: The aim of this study was to assess the immediate and delayed effects of tear punctal occlusion with punctal plugs on tear meniscus height (TMH) in severe aqueous-deficient dry eye (ADDE) disease. METHODS: Consecutive patients with severe ADDE related to Sjögren syndrome or ocular graft-versus-host disease underwent inferior and superior occlusion with punctal plugs. TMH was measured using the LacryDiag ocular surface analyzer platform before, 10 minutes, and at least 1 month after punctal occlusion. The corneal fluorescein staining (CFS) score was graded with the Oxford scale (from 0 to 5). Ocular symptoms were graded with a visual analog scale (from 1 to 10). RESULTS: We included 24 eyes of 24 patients (mean age 61 ± 9 years; mean follow-up 7 ± 5 months). The mean TMH was 0.19 ± 0.06 mm at baseline and increased significantly to 0.41 ± 0.13 mm ( P < 0.001) and 0.46 ± 0.17 mm ( P < 0.001) at 10 minutes after punctal plug insertion and at the end of follow-up, respectively. The median CFS score decreased from 3 ± 1 before plug insertion to 1 ± 2 at the end of follow-up ( P < 0.001). Many patients (67%; n = 16) reported subjective improvement of symptoms. TMH was negatively correlated with the CFS score and visual analog scale score assessing symptoms. CONCLUSIONS: Upper and lower punctal occlusion increased TMH in patients with severe ADDE as soon as 10 minutes after plug insertion. TMH remained stable over time, which led to the relief of symptoms and reduced corneal staining.

Conjunctival and Limbal Conjunctival Autograft vs. Amniotic Membrane Graft in Primary Pterygium Surgery: A 30-Year Comprehensive Review.

INTRODUCTION: The purpose of this study is to compare the "real-life" effectiveness of amniotic membrane graft (AMG) and conjunctival (CAT) or limbal conjunctival (LCA) autograft in the management of primary pterygium. METHODS: Human-based studies on primary pterygium surgery that were published between 1993 and 2022 with at least 3 months of follow-up were identified, and only those that were retrospective were included. The global recurrence rate of pterygium was assessed for each surgical technique separately. Specific recurrence rates taking into consideration the fixation technique (glue versus sutures) were also measured. RESULTS: 35 real-life retrospective subgroups comprising a total of 3747 eyes were included in the final review. The mean global recurrence rates for CAT, LCA and AMG were 7.61%, 5.50% and 9.0%, respectively. Recurrences were less common for patients who received fibrin glue (5.92%, 2.56% and 3.60%) than for those who received sutures (8.99%, 6.03% and 23.0%) for the three groups, respectively. Surgical techniques combining CAT or LCA with AMG yielded an even lower global recurrence rate (1.83%). CONCLUSION: AMG seems like a reasonable option that could be considered in primary pterygium surgery, especially when glued to the underlying sclera. Combining AMG with other treatment modalities such as CAT or LCA seems to offer an interesting alternative in terms of recurrence.

Double-Docking Technique for Femtosecond Laser-Assisted Deep Anterior Lamellar Keratoplasty: A Retrospective Consecutive Case Series Study of Advanced Keratoconus.

PURPOSE: The aim of this study was to report the clinical outcomes and prognosis of femtosecond laser (FSL)-assisted double-docking deep anterior lamellar keratoplasty (DD-DALK) for advanced keratoconus (AK). METHODS: Records of consecutive patients with keratoconus who underwent FSL-assisted DALK (DD-DALK) were reviewed. RESULTS: We analyzed 37 eyes from 37 patients who underwent DD-DALK. Sixty-eight percent of eyes had a successful big-bubble formation and 27% had a manual dissection to achieve the DALK deep dissection. Stromal scarring was associated with not achieving a big bubble. Intraoperative conversion to penetrating keratoplasty was conducted in 2 cases (5%). The best-corrected visual acuity improved from a median (± interquartile range) of 1.55 ±0.25 logMAR preoperatively to 0.2 ±0.2 logMAR ( P < 0.0001). The median postoperative spherical equivalent was -5.75 ±2.75 D with a median astigmatism of -3.5 ±1.3 D. BCVA, SE, and astigmatism were not statistically different between patients who underwent DD-DALK and patients who underwent manual DALK. Stromal scarring was associated with big-bubble (BB) formation failure ( P = 0.003). All patients with failed BB requiring manual dissection had anterior stromal scarring. CONCLUSIONS: DD-DALK is safe and reproducible. The success rate of BB formation is hampered by stromal scarring.

Cystoid macular oedema after descemet membrane endothelial keratoplasty.

AIMS: To determine the incidence and risk factors of cystoid macular oedema (CMO) following descemet membrane endothelial keratoplasty (DMEK) with or without combined cataract surgery (triple-DMEK). METHODS: We reviewed the records of patients who underwent DMEK surgery alone or triple-DMEK performed at the Rothschild Foundation Hospital (Paris, France) between January 2019 and March 2020. Patients with pre-existing CMO observed on the preoperative macular optical coherence tomography (OCT) were excluded. Spectral-domain OCT was performed in patients with postoperative visual impairment. Data regarding comorbidities, intraoperative characteristics and postoperative treatments or complications were collected and analysed. Univariate and multivariate analyses were performed. RESULTS: Twenty three of 246 eyes (9.36%) developed clinically significant (cs)-CMO after DMEK. Triple-DMEK was not associated with a higher risk to develop CMO (12.2% in DMEK alone and 6.1% in triple-DMEK). Pseudophakic bullous keratopathy (PBK ; 39.1% vs 9%; OR=3.5 (1.0 to 11.8), p=0.045) and epiretinal membrane (ERM; 39.1% vs 7.7%; OR=10.5 (3.4 to 32.3), p<0.001) were more frequently observed in patients who developed CMO. The occurrence of hyphaema during surgery was statistically associated with postoperative CMO (13% vs 1.3%; OR=7.1 (1.0 to 48.8) p=0.045). Peroperative epithelial debridement was statistically associated with postoperative CMO (65.2% vs 33.2%, p=0.005), but only in univariate analysis. CONCLUSIONS: We identified a clinically significant CMO incidence of 9.35% after DMEK. Patients with a history of ERM, PBK and intraoperative hyphaema may be at risk of developing CMO after DMEK surgery and should be monitored.

Detecting Subclinical Corneal Edema Using Corneal Thickness Mapping in Patients Presenting Fuchs Endothelial Corneal Dystrophy.

PURPOSE: To determine whether local corneal thickness changes observed with optical coherence tomography (OCT) can detect subclinical corneal edema in Fuchs endothelial corneal dystrophy (FECD). SETTING: Retrospective cohort study. METHODS: A series of patients presenting FECD who underwent cataract surgery alone (45 eyes) or with concomitant Descemet membrane endothelial keratoplasty (triple procedure; 117 eyes). The study reviewed medical records, collected the preoperative corneal thickness map and calculated the differences and ratio of corneal thickness measured at 5, 7, and 9 mm from the central corneal thickness. Area under the receiver operating characteristic curves (AUCs) were calculated and thresholds were selected to obtain a specificity of 90%. RESULTS: The median difference between 5- and 2-mm corneal thickness in the supra-nasal quadrant (∆5-2mmSN) was 38 µm (interquartile range 34-46) in the cataract group and 17 µm (2-38) in the triple procedure group (P < .001). The corneal thickness ratios of supra-nasal 5- to 2-mm (R5/2mmSN) and 7- to 2-mm (R7/2mmSN) were 1.07 (1.06-1.08) and 1.15 (1.13-1.17)] in the cataract group and 1.03 (1.00-1.06) and 1.09 (1.06-1.14) in the triple procedure group (P < .001). The probability of corneal edema was increased 7-fold with ∆5-2mm SN < 27 µm (AUC = 0.76) and 9.4- and 7.4-fold with R5/2mmSN and R7/2mmSN < 1.045 (AUC = 0.77) and 1.118 (AUC = 0.76), respectively. CONCLUSIONS: Local changes in corneal thickness may be useful in detecting preclinical corneal edema, especially in patients with FECD undergoing cataract surgery.

An Efficient Technique for the Long-term Preservation of SMILE Lenticules Using Desiccation.

PURPOSE: To evaluate a desiccation protocol for the long-term preservation of human small incision lenticule extraction (SMILE) lenticules and to study their integration in an in vivo rabbit model. METHODS: Lenticules were retrieved after SMILE procedures in patients, then desiccated according to a novel protocol. Histologic and electron microscopic analyses were performed. Six rabbit eyes received grafts with an inlay technique, which consisted of inserting a desiccated lenticule into a stromal pocket. Rabbits were killed at different times between 6 and 24 weeks. Rabbit corneas were analyzed using optical coherence tomography, histology, and DAPI staining. RESULTS: Microscopic analysis of desiccated lenticules showed a preserved stromal architecture after rehydration. A decellularization of the lenticules after desiccation was observed without any chemical treatment. All rabbit corneas remained clear after grafting human lenticules and no rejection occurred. Optical coherence tomography showed regular lenticular implantation and no decrease in lenticule thickness. Histologic analysis showed no inflammatory infiltration around lenticules and no nuclear material inside lenticules after 6 months. CONCLUSIONS: A favorable integration of desiccated human SMILE lenticules in rabbit corneas was observed. The refractive issue of lenticular implantation must be investigated next. Clinical trials are needed to evaluate the use of desiccated SMILE lenticules to treat hyperopia or keratoconus in humans. [J Refract Surg. 2023;39(7):491-498.].

Multiple Evanescent White Dot Syndrome Following COVID-19 mRNA Vaccination.

PURPOSE: To report two cases of multiple evanescent white dot syndrome (MEWDS) following COVID-19 vaccination with the BNT162b2 mRNA vaccine. METHODS: Two case reports. Case-1: A 40-yo Caucasian male, complained of blurred and decrease of vision in his left eye (OS) one week after the first dose of the BNT162b2 mRNA SARS-CoV-2 vaccine. Funduscopic examination OS showed multiple granular white dots with an aspect of foveal granularity. Case-2: A 23-yo woman also presented with defective and decrease of vision OS. She received her first dose of the BNT162b2 mRNA SARS-CoV-2 vaccine ten days before. Dilated fundus examination OS showed altered macular reflex with an aspect of foveal granularity. RESULTS: Multimodal imaging showed features of MEWDS in both cases. The anomalies found resolved spontaneously after 6 weeks. CONCLUSION: Inflammation and immune dysregulation induced by COVID-19 mRNA vaccine or its adjuvants could be involved in ocular adverse effects.

Ocular sequelae of epidermal necrolysis: French national audit of practices, literature review and proposed management.

Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) are serious and rare diseases, most often drug-induced, and their incidence has been estimated at 6 cases/million/year in France. SJS and TEN belong to the same spectrum of disease known as epidermal necrolysis (EN). They are characterized by more or less extensive epidermal detachment, associated with mucous membrane involvement, and may be complicated during the acute phase by fatal multiorgan failure. SJS and TEN can lead to severe ophthalmologic sequelae. There are no recommendations for ocular management during the chronic phase. We conducted a national audit of current practice in the 11 sites of the French reference center for toxic bullous dermatoses and a review of the literature to establish therapeutic consensus guidelines. Ophthalmologists and dermatologists from the French reference center for epidermal necrolysis were asked to complete a questionnaire on management practices in the chronic phase of SJS/TEN. The survey focused on the presence of a referent ophthalmologist at the center, the use of local treatments (artificial tears, corticosteroid eye drops, antibiotic-corticosteroids, antiseptics, vitamin A ointment (VA), cyclosporine, tacrolimus), the management of trichiatic eyelashes, meibomian dysfunction, symblepharons, and corneal neovascularization, as well as the contactologic solutions implemented. Eleven ophthalmologists and 9 dermatologists from 9 of the 11 centers responded to the questionnaire. Based on questionnaire results, 10/11 ophthalmologists systematically prescribed preservative-free artificial tears, and 11/11 administered VA. Antiseptic or antibiotic eye drops or antibiotic-corticosteroid eye drops were recommended as needed by 8/11 and 7/11 ophthalmologists, respectively. In case of chronic inflammation, topical cyclosporine was consistently proposed by 11/11 ophthalmologists. The removal of trichiatic eyelashes was mainly performed by 10/11 ophthalmologists. Patients were referred to a reference center for fitting of scleral lenses (10/10,100%). Based on this practice audit and literature review, we propose an evaluation form to facilitate ophthalmic data collection in the chronic phase of EN and we also propose an algorithm for the ophthalmologic management of ocular sequelae.

EMMPRIN modulates epithelial barrier function through a MMP-mediated occludin cleavage: implications in dry eye disease.

Dry eye is a common disease that develops as a result of alteration of tear fluid, leading to osmotic stress and a perturbed epithelial barrier. Matrix metalloproteinase-9 (MMP-9) may be important in dry eye disease, as its genetic knockout conferred resistance to the epithelial disruption. We show that extracellular matrix metalloproteinase inducer (EMMPRIN; also termed CD147), an inducer of MMP expression, participates in the pathogenesis of dry eye through MMP-mediated cleavage of occludin, an important component of tight junctions. EMMPRIN expression was increased on the ocular surface of dry eye patients and correlated with those of MMP-9. High osmolarity in cell culture, mimicking dry eye conditions, increased both EMMPRIN and MMP-9 and resulted in the disruption of epithelial junctions through the cleavage of occludin. Exogenously added recombinant EMMPRIN had similar effects that were abrogated in the presence of the MMP inhibitor marimastat. Membrane occludin immunostaining was markedly increased in the apical corneal epithelium of both EMMPRIN and MMP-9 knock-out mice. Furthermore, an inverse correlation between EMMPRIN and occludin membrane staining was consistently observed both in vitro and in vivo as a function of corneal epithelial cells differentiation. These data suggest a possible role of EMMPRIN in regulating the amount of occludin at the cell surface in homeostasis beyond pathological situations such as dry eye disease, and EMMPRIN may be essential for the formation and maintenance of organized epithelial structure.

Glycogene Expression Profile of Human Limbal Epithelial Cells with Distinct Clonogenic Potential.

Glycans function as valuable markers of stem cells but also regulate the ability of these cells to self-renew and differentiate. Approximately 2% of the human genome encodes for proteins that are involved in the biosynthesis and recognition of glycans. In the present study, we evaluated the expression of a small subset of glycogenes in human limbal epithelial cells with distinct clonogenic potential. Individual clones were classified as abortive or clonogenic, based on the fraction of the terminal colonies produced; clones leading exclusively to terminal colonies were referred to as abortive while those with half or fewer terminal colonies were referred to as clonogenic. An analysis of glycogene expression in clonogenic cultures revealed a high content of transcripts regulating the galactose and mannose metabolic pathways. Abortive clones were characterized by increased levels of GCNT4 and FUCA2, genes that are responsible for the branching of mucin-type O-glycans and the hydrolysis of fucose residues on N-glycans, respectively. The expansion of primary cultures of human limbal epithelial cells for 10 days resulted in stratification and a concomitant increase in MUC16, GCNT4 and FUCA2 expression. These data indicate that the clonogenic potential of human limbal epithelial cells is associated with specific glycosylation pathways. Mucin-type O-glycan branching and increased fucose metabolism are linked to limbal epithelial cell differentiation.

Clinical, Meibographic, and Interferometric Evaluation in Children With Ocular Rosacea.

PURPOSE: To describe clinical, meibographic, and interferometric signs in children with ocular rosacea. DESIGN: Prospective case-control study. METHODS: This single-center study at the Fondation Ophtalmologique Rothschild (Paris, France) included 42 children with ocular rosacea and 44 healthy volunteers (median ages of 10 and 11 years old, respectively) who had infrared meibography images of their lower lids and tear lipid layer thickness measurements taken with the LipiView II device (Tearscience). Clinical severity was graded on a 0 to 4 scale and compared with meiboscores (range 0-4) and tear film lipid layer thickness (range 0-100 nm). RESULTS: Seven patients presented with unilateral disease and 29 had an asymmetrical form. Twenty-four patients had associated cutaneous rosacea. Ten of 84 eyes presented with a loss of vision <20/25. The mean clinical severity grade was 2.5 ± 1.4. Meibographic abnormalities were significantly more important in children with ocular rosacea (mean meiboscore 2.1 ± 1.36) than in healthy volunteers (0.61 ± 0.78, P < .001). Clinical severity (r = 0.44, P < .001), duration of disease (r = 0.28, P = .011), and a history of chalazia (r = 0.30, P = .006) were correlated to meibographic severity. Mean lipid layer thickness was not significantly different between cases and controls (74.4 ± 18.7 nm and 76.6 ± 18 nm, respectively, P = .47). CONCLUSION: Meibomian structural alterations in children can be severe and are correlated to ocular rosacea severity. Meibography is an essential tool for diagnosis and follow-up, whereas the contribution of tear film interferometry is uncertain.

Meganuclease targeting HSV-1 protects against herpetic keratitis: Application to corneal transplants.

Herpes simplex virus (HSV) infection is a leading cause of corneal blindness. However, keratoplasty is only rarely proposed due to the high frequency of graft failure and associated recurrences. Gene therapy of the corneal graft might provide sustained protection against HSV infection. To test that hypothesis, we designed a meganuclease specific to an HSV-1 DNA sequence coding for major capsid protein (UL19) and selected an adeno-associated virus type-2 as the vector. Meganuclease was transduced into corneas and its effect was challenged in vitro, ex vivo, and then in vivo in a rabbit HSV-1-infection model of stromal keratitis and endotheliitis. In vivo, meganuclease exposure resulted in fewer infected stromal and endothelial cells, and protected against corneal opacification and edema. Ex vivo, HSV-1 infection rates of meganuclease-treated human corneas were drastically reduced. Furthermore, genetically engineered corneas transplanted in vivo into rabbit eyes protected against HSV-1 infection. This genome-editing technology targeting HSV-1 opens new opportunities to manage severe post-herpetic corneal blindness by providing infected patients with genetically protected corneal transplants.

Clinical course and treatment of archipelago keratitis: a Herpesviridae keratitis subtype.

PURPOSE: Archipelago keratitis (ApK) is a subtype of Herpesviridae stromal keratitis that consists of subepithelial nummular inflammatory infiltrates arranged in a radial centripetal pattern. This rare and poorly described form is not often recognised early. We report the first large series of ApK, with an analysis of clinical settings at presentation, evolution of the disease with time and a description of factors associated with recurrence. METHODS: The clinical records of 82 patients (83 eyes) with a diagnosis of ApK between 2011 and 2021 in two centres were reviewed. RESULTS: The median age of the 82 patients at referral was 37±28 years. ApK was unilateral in all but one case. A total of 76% of patients had at least one second diagnostic criteria suggesting a herpetic aetiology. Overall, 44 (53%) eyes exhibited least one recurrence after a median of 12 months. Recurrence was frequently associated with neovascularisation (HR 2.1, 95% CI 1.1 to 3.9; p=0.02) and tapering corticosteroids (HR 3.5, 95% CI 1.8 to 7.1; p<0.01) or valaciclovir use (HR=2.3, 95% CI 1.2 to 4.6; p=0.01). Antiviral treatment was used in all patients, whereas local anti-inflammatory drugs such as corticosteroids and/or ciclosporin were used in 73 (88%) cases. CONCLUSION: ApK is a Herpesviridae stromal keratitis that is typically unilateral in presentation and features a high risk of recurrence. Combined treatment with antiviral and anti-inflammatory drugs are usually required over the long term. Topical ciclosporin can be useful as a corticosteroid-sparing treatment.