Accelerated Corneal Crosslinking to Arrest Progression of Corneal Ectasia: A Prospective Multicenter Study.

OBJECTIVES: To report the results of epithelium-off accelerated corneal collagen crosslinking (accelerated corneal crosslinking [ACXL]) in patients with progressive keratoconus. METHODS: This prospective, nonrandomized, noncomparative, interventional, multicenter clinical study included all patients who underwent ACXL, either continuous (c-ACXL; 9 mW/cm 2 , 10', 5.4 J/cm 2 ) or pulsed (p-ACXL; 2″ON/1″OFF, 30 mW/cm 2 , 4.5', 5.4 J/cm 2 ) between January 2014 and May 2017. Best-corrected visual acuity, sphere, cylinder, spherical equivalent, and topographical keratometry data were collected preoperatively and at 1, 3, 6, 12, 18, and 24 months postoperatively. RESULTS: Ninety-six eyes of 78 patients were included. The mean age was 20.8±4.4 years (14-33) for c-ACXL and 26.7±7.7 years (12-37) for p-ACXL. The mean best-corrected visual acuity was 0.4±0.4 for c-ACXL and 0.01±0.1 for p-ACXL preoperatively, and 0.3±0.3 ( P =0.0014) and -0.01±0.1 ( P =0.1554), respectively, at the last follow-up. The subjective sphere and spherical equivalent did not show statistically significant differences between the time points ( P >0.05). The subjective cylinder showed significant differences ( P =0.0013 for c-ACXL; P =0.0358 for p-ACXL). Keratometric values (K steep , K flat , and SimK) remained stable, with no statistically significant differences ( P >0.05). No major complications were noted. CONCLUSIONS: Both c-ACXL and p-ACXL are equally safe and effective ACXL protocols in stabilizing the progression of keratoconus and can be considered alternatives to the conventional Dresden protocol.

Corneal Neuropathic Pain: A Patient and Physician Perspective.

Corneal neuropathic pain (CNP) is a debilitating condition characterized by pain in the absence of a noxious stimulus. Symptoms such as ocular stinging, burning, photophobia, irritation, and a deep aching pain can be severe despite a seemingly normal ocular surface on examination. CNP may develop due to either peripheral or central sensitization. Peripheral sensitization develops due to aberrant regeneration of corneal nociceptors and nerve fibers as a result of corneal injury or disease of peripheral corneal nerves. Whereas, central sensitization develops due to upregulation of excitatory neurotransmitters as a result of chronic inflammation, which leads to amplification of neuronal response to stimuli. Unfortunately, due to the disparity in severity of symptomology and the observable signs on examination, patients' symptoms are commonly thought to be "psychological" or "functional", and patients report feeling ignored and neglected. Additionally, diagnosis is often delayed which adversely affects patient outcomes. Research to date has focused on the scientific aspects of corneal neuropathic pain: its pathophysiology, epidemiology, investigations, and management. Research into the patient personal experience and the challenges faced by individual patients and their clinicians is lacking. We present the patient and physician perspective on the journey of both patients in order to provide insights into the challenges faced by patients and physicians in the diagnosis, assessment, and management of corneal neuropathic pain.

Corneal neuropathic pain is a rare disease that causes patients to experience severe eye pain without a painful stimulus. Patients often experience one or more symptoms, such as ocular stinging, burning, irritation, photophobia, and deep aching pains even though ophthalmologists cannot see any abnormality when they examine the eyes. Due to a significant lack of awareness and understanding of the condition, diagnosis is often delayed and patients are left feeling ignored or neglected. Research to date has focused on the scientific aspects of corneal neuropathic pain such as what causes it, the tests doctors use to diagnose it, and the best treatments to manage it. In this article, we present the patient and physician perspective, an understanding of which we believe can improve the care that patients receive and can promote awareness and understanding of the condition, facilitating early diagnosis and treatment.

Severe chemical eye injuries - clinical outcomes and associated socio-economic factors.

Aims: To describe clinical outcomes, management, and socio-economic impact of severe acute chemical eye injuries in a tertiary hospital. Methods: 37 patients required emergency admission to the Royal Victoria Infirmary eye ward between April 2013 and September 2015. Demographics, best corrected distance visual acuity (BCDVA), causative agent, degree of limbal stem cell deficiency (LSCD), management and socio-economic data were evaluated. Results: Mean age on admission was 34.5 years (SD 16.3; range 16-82); 30 males (81.1%); 22 bilateral (59.5%). Causative agent: alkali in 30 cases (81.1%); acid in three cases (8.1%); and unknown in four cases (10.8%). Fifteen cases (40.5%) were assaults, 12 (32.5%) work-related accidents, nine (24.3%) domestic accidents and one (2.7%) undetermined. Eleven patients (29.7%) were unemployed, 18 (48.6%) were labourers, three (8.1%) were students, three (8.1%) were retired and two (5.4%) were professionals. Mean admission time was five days (SD 3.2; range 1-12). Mean follow-up time was 170.5 days (range 1-946). Mean cost of admission was £2478 (range £274-5785). Five patients (13%; seven eyes) developed total or partial limbal stem cell deficiency, all being assaults. Conclusions: Main causative agent in our study was alkali, with young men in the working age being most frequently involved. Many patients required prolonged hospital admission and costly follow-up. The majority of cases were assaults, mostly occurring in unemployed patients. All the limbal stem cell deficiency cases were due to assaults. We believe that socio-economic factors play an important role in the cause, severity and cost of chemical eye injuries. Lay Summary: Acute chemical eye injuries have a significant and extensive impact on patients' visual function outcomes and vision-related quality of life, with consequent enormous burden to affected individuals, their families and society. We believe that by understanding the socio-economic environment, we may not only be able to enforce safety measures to tackle the increasing rate of severe chemical eye injuries in our community, but also to develop collaborative programmes with the community, educating the population on the seriousness of chemical eye injuries, and with the local authorities, trying to understand the clustering of assaults in areas and tackling the associated socio-economic risk factors, such as unemployment. Given the increasing rate of assaults using chemicals in recent times, it is also important to assess availability of adequate victim support programmes and develop good interaction with relevant local, regional and national authorities to ensure all aspects of community security service are in place to be able to address any potential deficiencies in line with police and home office guidelines. Keeping in mind that the best action plan is always prevention. However, when an ocular injury does occur it is evident that significant morbidity and visual sequelae can result and affect the socio-economic status of the victims despite our best current medical and surgical care.

Outcomes of N-butyl-2-Cyanoacrylate Tissue Adhesive Application in Corneal Perforation Disorders: Consecutive Case Series.

INTRODUCTION: The purpose of this study was to report the success and long-term outcomes of cyanoacrylate tissue adhesive (CTA) application in the management of corneal perforation disorders. METHODS: This retrospective case series describes the profile and outcomes of eyes that underwent CTA for corneal perforation over an 11-year period from January 2009 until January 2020 at a tertiary eye centre in the United Kingdom. RESULTS: In total, 25 eyes underwent CTA application during the study period. Non-traumatic sterile corneal melt was responsible in more than half of the cases (56.0%; n = 14) followed by infection (32.0%; n = 8) and trauma (12.0%; n = 3). Median size of perforation was 2.0 mm (interquartile range, IQR 1.0-3.0). The most common anatomical location of corneal perforation was central (56.0%; n = 14). Ocular surface disease was seen in almost all eyes except two (92.0%; n = 23) with dry eye disease being the most common (48.0%; n = 12). Amongst 23 eyes that completed follow-up (median 27 months; IQR 9.5-46.5), single CTA application was successful in achieving intact globe in 13 (56.5%) eyes and repeat gluing sealed total of 20 (86.9%) eyes. Survival analysis showed cumulative success of 71.0% and 51.2% at 90 and 250 days, respectively. The CTA was retained in the eyes for median of 94.0 days (IQR 30.0-140.5). A total of five patients developed adverse events, including endophthalmitis (n = 2), following CTA application. CONCLUSIONS: CTA was highly effective in sealing corneal perforations in acute setting and showed moderate long-term success. However, multiple applications are often required.

Dupilumab induced ocular surface disease: A prospective case series.

PURPOSE: To identify the incidence, risk factors, demographics, and clinical profile of dupilumab-induced ocular surface disease (DIOSD) in patients with atopic dermatitis (AD), propose a standardised treatment protocol (STP) and evaluate the response. METHODS: Prospective case series of AD patients treated in the Dermatology Department, Royal Victoria Infirmary, Newcastle upon Tyne, UK developing ocular symptoms after commencing Dupilumab between September 2018 and February 2020. A standard history and examination protocol were used including subjective symptom severity grading and Ocular Surface Disease Index (OSDI) questionnaire on each visit. Standard treatment was prescribed, and response evaluated. RESULTS: 32 of 113 included patients (28.31%) developed DIOSD, of which 20 (62.5%) were referred to the Cornea Service. Median age was 38.0 years (IQR 26.8; range 19-74). Male to female ratio was 1:1. Average time to onset of ocular symptoms from starting dupilumab was 9.2 weeks (IQR 8.8; range 0.1-40). 90% patients had bilateral conjunctival inflammation and blepharitis at presentation. Significant improvement in the subjective severity scale and the median OSDI score (from 34.0 to 10.2) was noted in response to topical eye treatment. Dupilumab was discontinued in none. CONCLUSIONS: DIOSD is not uncommon although, with timely referral and appropriate topical treatment better clinical outcome and patient satisfaction can be achieved without the need to discontinue Dupilumab. Prior allergic conjunctivitis did not affect the incidence or severity of DIOSD. Further prospective studies with longer follow-up and more focus on possible disease mechanism such as goblet cell related changes and immune response are needed.

International survey on dry eye diagnosis by experts.

Purpose: To evaluate patterns and opinion from international experts with respect to dry eye disease (DED) diagnosis in clinical practice. Methods: An online survey was distributed to worldwide DED experts. The use of diagnosis tests was evaluated including: symptoms questionnaires, functional tests, tear stability, tear volume, tear composition, surface damage and inflammation, and eyelid assessment. After the subjective importance of symptoms, tear break up time (TBUT), non-invasive TBUT, Schirmer's test, tear meniscus height, tear osmolarity, tear metalloproteinase 9, blepharitis assessment and non-contact meibography was evaluated according to likert scale. Results: The survey was sent to 109 experts, and 77 completed the questionnaire (rate of response = 70.6%). Most of the participants were from North America (27%) and Europe (40%). A majority of respondents (73%) diagnose DED using clinical signs and symptoms, but not fulfilling a specific criteria. Seventy-six participants (98.7%) use symptoms questionnaires. All participants evaluate damage to ocular surface, and fluorescein staining is the most frequent method used (92%). Also, all the respondents perform meibomian gland and blepharitis assessment. On the other hand, only 69.8% evaluate tear composition, being osmolarity the most common test used (66.2%). Regarding to the importance of tests, TBUT (p = 0.002) and Schirmer's (p = 0.021) were found to be more important to experts from Europe than North America. No differences were found in any other test (p > 0.05). Conclusions: This survey offers updated and day-to-day diagnostic clinical practice by DED worldwide experts. The results highlight the importance of symptoms and clinical signs, but not necessarily following a strict criteria.

Differences in minimal disease knowledge of keratoconus patients: results from an international survey.

BACKGROUND/AIMS: The objective of this multicentre, multinational, prospective study was to assess the level of basic understanding that individuals with keratoconus possessed about their condition. METHODS: We recruited 200 active keratoconus patients who were under regular review, and cornea specialists established a standard of 'minimal keratoconus knowledge' (MKK) that included an understanding of the definition, risk factors, symptoms and treatment options for the condition. We collected data from each participant regarding their clinical characteristics, highest level of education, (para)medical background and experiences with keratoconus within their social circle, and calculated the percentage of MKK attained by each patient. RESULTS: Our findings revealed that none of the participants met the MKK standard, with the average MKK score being 34.6% and ranging from 0.0% to 94.4%. Furthermore, our study showed that patients with a university degree, previous surgical intervention for keratoconus or affected parents had a higher MKK. However, age, gender, disease severity, paramedical knowledge, disease duration and best-corrected visual acuity did not significantly affect the MKK score. CONCLUSIONS: Our study demonstrates a concerning lack of basic disease knowledge among keratoconus patients in three different countries. The level of knowledge exhibited by our sample was only one-third of what cornea specialists would typically anticipate from patients. This highlights the need for greater education and awareness campaigns surrounding keratoconus. Further research is needed to determine the most efficient approaches for enhancing MKK and subsequently improving the management and treatment of keratoconus.

Future directions in managing aniridia-associated keratopathy.

Congenital aniridia is a panocular disorder that is typically characterized by iris hypoplasia and aniridia-associated keratopathy (AAK). AAK results in the progressive loss of corneal transparency and thereby loss of vision. Currently, there is no approved therapy to delay or prevent its progression, and clinical management is challenging because of phenotypic variability and high risk of complications after interventions; however, new insights into the molecular pathogenesis of AAK may help improve its management. Here, we review the current understanding about the pathogenesis and management of AAK. We highlight the biological mechanisms involved in AAK development with the aim to develop future treatment options, including surgical, pharmacological, cell therapies, and gene therapies.

Minimally invasive corneal neurotization for neurotrophic keratopathy: The potential effect of age, denervation chronicity and lesion location.

Purpose: Neurotrophic keratopathy (NK) is an uncommon but challenging clinical condition characterized by altered corneal nerves and sensation leading to corneal damage. Corneal neurotization, a surgical technique that aims to "re-innervate" the cornea, has gained increasing popularity in view of the potential to permanently improve or even restore the normal corneal sensation. In this study, we aimed to report the outcomes of two cases of NK that underwent indirect minimally invasive corneal neurotization (MICN) with a sural nerve autograft, and to provide plausible explanations for the observed clinical outcomes. Observations: This was an interventional case series of two patients who underwent MICN for severe unilateral NK. The MICN technique was adapted from the technique originally described by Elbaz et al., in 2014. Clinical severity of NK was graded according to Mackie's grading system. Corneal sensation was measured using the Cochet-Bonnet esthesiometer (0-60mm) and corneal nerves were examined using in vivo confocal microscopy (IVCM) with Heidelberg HRT3 Rostock Corneal Module. Patient 1 was a 70-year-old man with a right grade III NK following trigeminal nerve decompression for trigeminal neuralgia. Patient 2 was a 62-year-old man with a left grade II NK following a left-sided acoustic neuroma resection. The denervation time was 23 years for both patients. Following the MICN surgery, none of the patients achieved sustained improvement in the corneal sensation (though patient 1 achieved a transient improvement in central corneal sensation to 20mm at 4 months' postoperative before returning to 0mm at 6 months' postoperative). IVCM did not reveal any changes in the corneal nerve density and morphology post-MICN. Conclusions and Importance: Based on our observations and the literature, we postulate that long denervation time, proximal injury to the trigeminal nerve and older patient age may serve as poor prognostic factors for MICN. As CN is being increasingly adopted in clinical practice for treating NK, understanding of these potential factors will facilitate better risk-benefit stratification and patient counselling. Future larger studies are required to elucidate these findings.

Understanding Ocular Surface Inflammation in Tears Before and After Autologous Cultivated Limbal Epithelial Stem Cell Transplantation.

INTRODUCTION: We aimed to determine the expression of inflammatory cytokines in the tears of patients with unilateral total limbal stem cell deficiency (TLSCD) caused by chemical burns before and after autologous cultivated limbal epithelial stem cell transplantation (CLET). METHODS: Tear samples were collected from both eyes of 23 patients with unilateral TLSCD and 11 healthy controls, at fixed timepoints before and after CLET. Dissolved molecules were extracted from Schirmer's strips using a standardised method and analysed on an array plate of ten inflammatory cytokines (V-Plex Proinflammatory Panel 1 Human Kit, MSD). RESULTS: IL1ß expression was significantly elevated in the TLSCD eye compared with the unaffected eye at baseline (p < 0.0001) but decreased to normal 3 months post-CLET (p = 0.22). IL6 and IL8 were unaffected at baseline but significantly elevated in the TLSCD eyes at 1 month post-CLET (p = 0.001 and p < 0.0001, respectively). IL6 returned to normal at 3 months and IL8 at 6 months post-CLET. There was a significant renewed increase in IL1ß, IL6 and IL8 expression at 12 months post-CLET (p < 0.0001, p = 0.0001 and p = 0.0003, respectively). IFNγ, IL10 and IL12p70 expression were significantly reduced in both eyes of patients with unilateral TLSCD at all timepoints. CONCLUSION: IL1ß is a specific marker of inflammation in TLSCD eyes that could be therapeutically targeted pre-CLET to improve stem cell engraftment. At 12 months post-CLET the spike in levels of IL1ß, IL6 and IL8 coincides with cessation of topical steroids, suggesting ongoing subclinical inflammation. We therefore recommend not discontinuing topical steroid treatment in cases where penetrating keratoplasty is indicated; however, further investigation is needed to ascertain this. TRIAL REGISTRATION: European Union Drug Regulating Authorities Clinical Trials Database (EuDRACT 2011-000608-16); ISRCTN (International Standard Randomised Controlled Trial Number (isrctn51772481).

National survey of corneal cross-linking (CXL) practice patterns in the United Kingdom during 2019.

OBJECTIVE: To provide an insight into trends in corneal cross-linking (CXL) practice in the UK, including criteria for progression of corneal ectasia, identification of patients for CXL, the CXL procedure itself and post-operative management. METHODS: All ophthalmologist members of the UK Cross-linking (UK-CXL) Consortium were invited to complete an online survey about CXL practice for the year 2019. The data collected was anonymised by site and analysed with descriptive statistics. RESULTS: Responses were received from 16 individual CXL centres (16/38; 42% response rate) and the data represented ~2,000 CXL procedures performed in the UK in 2019. The commonest indication for CXL was progressive keratoconus. Between centres, there were variations in diagnostic evaluation, patient selection for CXL, the CXL procedure and the pre- and post-operative monitoring of patients. CONCLUSION: Consistent with the wide number of CXL treatment techniques described in the published literature world-wide, variations in the monitoring of corneal ectasia, indications for CXL, CXL practice and post-CXL follow-up were found to exist between UK-based CXL centres.

Long-Term Graft Survival and Decline in Endothelial Cell Density Following Penetrating Keratoplasty with Organ-Cultured Corneas.

INTRODUCTION: Endothelial cell density (ECD) changes long after penetrating keratoplasty (PKP) of organ-cultured corneas have been little studied. We aim to calculate the point when ECD decline stabilises following PKP with organ culture stored corneas. METHODS: This is an observational study of first-ever PKPs and first-ever re-grafts, performed over 17 years under a single surgeon. ECDs were acquired at 3 and 6 months, 1 year post-graft and annually thereafter by specular microscopy. Time-dependent ECD data was fitted to a log-biexponential model. RESULTS: We studied 465 first-ever grafts and 128 re-grafts. Mean recipient age was 59 years (range 0-96 years; SD 22). Median follow-up was 5.7 (range 0.2-17.1) years. Probability of ED at 5 years in first grafts and re-grafts was 4.4% (2.6-7.1%) and 14.8% (8.3-23.2%). In first grafts, ECD loss reached 0.6% per annum at 7.9 (6.2-9.6) years post-operatively. The half-lives of ECD loss during the immediate post-operative period for first grafts, re-grafts, dystrophies, ectasias, and previous ocular surgery are 20.1 (14.9-30.9), 12.8 (6.9-79.4), 19.5 (13.1-37.7), 26.2 (16.2-68), and 11.6 (6.7-41.3) months, respectively. The half-life during this rapid phase of ECD loss has an inverse correlation with graft survival at 10 years (r = - 0.89, p = 0.02). CONCLUSIONS: Rate of endothelial decompensation is higher in first grafts than re-grafts. ECD decline stabilises 7.9 years post-operatively in first grafts but then becomes lower than the physiological loss expected. Further work is needed to verify whether organ-cultured grafts reach physiological levels of ECD loss faster than hypothermically stored grafts.

Efficacy of Lifitegrast Ophthalmic Solution, 5.0%, in Patients With Moderate to Severe Dry Eye Disease: A Post Hoc Analysis of 2 Randomized Clinical Trials.

IMPORTANCE: An investigation of the treatment effect of lifitegrast ophthalmic solution, 5.0%, in different subgroups by severity of dry eye disease (DED) seems warranted. OBJECTIVE: To explore the heterogeneity across different subgroups of DED and identify which participants were most likely to achieve clinically meaningful benefit with lifitegrast treatment. DESIGN, SETTING, AND PARTICIPANTS: This post hoc responder analysis was performed using the data from the phase 3 OPUS-2 and OPUS-3 studies, which were 12-week, prospective, double-masked, multicenter, placebo-controlled, randomized, parallel-arm clinical trials that previously demonstrated the efficacy of lifitegrast in DED. Pooled data were stratified into 4 subgroups based on severity of inferior corneal staining score (ICSS; ≤1.5 vs >1.5) and eye dryness score (EDS; <60 or ≥60) at baseline. Data were collected from December 7, 2012, to October 5, 2015, and post hoc analysis was performed from April 14, 2020, to July 30, 2021. INTERVENTIONS: Lifitegrast or placebo twice daily for 84 days. MAIN OUTCOMES AND MEASURES: Proportion of participants with (1) a clinically meaningful improvement in signs (ICSS or total corneal staining score [TCSS]) and symptoms (EDS or global visual analog scale [VAS]) and (2) a composite response for a given sign and symptom end point pair at day 84 were measured. Clinically meaningful improvement was defined as at least 30% improvement in symptoms (EDS or global VAS) and either at least a 1-point improvement in ICSS or at least a 3-point improvement in TCSS. For the composite responder analysis, the end point pairs were defined as at least a 30% reduction in EDS and at least a 1-point improvement in ICSS; at least a 30% reduction in EDS and at least a 3-point improvement in TCSS; at least a 30% improvement in global VAS and at least a 1-point improvement in ICSS; and at least a 30% improvement in global VAS and at least a 3-point improvement in TCSS. RESULTS: In total, 1429 participants (716 in the placebo group and 713 in the lifitegrast group) were analyzed (1087 women [76.1%]; mean [SD] age, 58.7 [14.3] years). For the overall pooled population, responder and composite responder rates favored lifitegrast vs placebo (odds ratio range, 1.29 [95% CI, 1.05-1.59] to 2.10 [95% CI, 1.68-2.61]; P ≤ .02). In the composite analysis, the subgroup with ICSS of greater than 1.5 and EDS of at least 60 at baseline (ie, moderate to severe DED) demonstrated a 1.70- to 2.11-fold higher odds of achieving clinically meaningful improvement with lifitegrast across all sign and symptom end point pairs (P ≤ .001). CONCLUSIONS AND RELEVANCE: These post hoc findings suggest that lifitegrast ophthalmic solution, 5.0%, treatment may be associated with a response in participants with moderate to severe signs and symptoms of DED. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02284516.

Referral Patterns of Patients with Limbal Stem Cell Deficiency to a Specialized Tertiary Center in the United Kingdom.

INTRODUCTION: Limbal stem cell deficiency (LSCD) is a potentially blinding disease; hence, referral to a specialist service is becoming increasingly common. Our aim was to investigate the referral patterns and associated details. METHODS: We conducted an audit of 100 consecutive patients with LSCD who were referred to our service from 2011 to 2018. Patient demographics, geographical location, cause of LSCD, coexisting ocular diseases, best corrected visual acuity (BCVA), and extent of LSCD were recorded. The following two subgroups were further analyzed: (1) burns and (2) other causes of LSCD. RESULTS: Out of the 100 patients (138 eyes), 70% were male, with a mean age of 45 years (SD 19). LSCD was unilateral in 62% of the cases. The most common ocular comorbidity was glaucoma, in 21 patients (33 eyes). Burns were the most frequent cause of referral (61%). The mean BCVA of the involved eye was 1.22 (SD 0.8) LogMAR, and total LSCD was present in 75 eyes (54%). There were statistically significant age, gender and eye-involved differences between the burns group and other causes group, mean 39 (SD 17) and 53 (SD 19) years (p < 0.001); 85% were men versus 48.7%, (p = 0.001); and 82% were unilateral versus 31% (p < 0.001), respectively. CONCLUSIONS: LSCD was more common in men and usually unilateral. Overall, the main cause of LSCD was burns. There were significant differences between the burns group and other causes of LSCD group in terms of age, gender and unilateral involvement that may help to guide management decisions.

The Enduring Experience in Dry Eye Diagnosis: A Non-Interventional Study Comparing the Experiences of Patients Living With and Without Sjögren's Syndrome.

INTRODUCTION: Previous studies have examined the patient experience regarding the diagnosis and management of dry eye disease (DED). The current study explored the ways in which the DED diagnostic pathway differs for those living with and without Sjögren's syndrome (SS), to identify aspects that influence the patient experience and associated quality of life (QoL). METHODS: An observational/descriptive, non-interventional, retrospective, self-reported online survey was conducted among adults living in France, Spain and Italy who were diagnosed with DED (with/without SS), were using topical DED treatments (≥ 6 months), and were not contact lens users. Recruitment was via an online database for non-SS participants and through local patient advocacy groups for SS respondents. RESULTS: The analysis included 827 respondents; 416 (50.3%) had SS and 82% were female. The mean age was 55 (SD 11; range 16-99) years. The mean age at diagnosis was 46 (SD 12; range 13-78) years and 50 (SD 10; range 21-73) years for SS and non-SS groups, respectively (p < 0.0001). The mean time to diagnosis was extended for SS participants [32 (SD 62) months] versus non-SS individuals [8.6 (SD 28) months (p < 0.0001)] and was associated with reduced QoL scores (r = 0.113; p = 0.0169). More SS participants (31%) consulted ≥ 4 healthcare professionals (HCPs) before DED diagnosis, versus non-SS individuals (6%) (p < 0.0001). Diagnosing clinician varied for SS respondents according to country, probably due to differences in healthcare systems/structures. More SS participants viewed their condition as a handicap than a discomfort, reporting greater QoL impact (p < 0.0001). CONCLUSIONS: Patient experiences in DED diagnosis vary substantially when comparing SS and non-SS individuals. Time to diagnosis significantly impacts QoL for SS patients, who see more HCPs ahead of DED diagnosis. The number of HCPs consulted before diagnosis and perceptions of DED are important for both groups. Country-specific variations highlight opportunities to improve consistency and efficiency across DED diagnostic pathways. These data should be considered alongside existing evidence from high-quality sources (e.g. clinical records).

In the eye of the storm: SARS-CoV-2 infection and replication at the ocular surface?

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first emerged in December 2019 and spread quickly causing the coronavirus disease 2019 (COVID-19) pandemic. Recent single cell RNA-Seq analyses have shown the presence of SARS-CoV-2 entry factors in the human corneal, limbal, and conjunctival superficial epithelium, leading to suggestions that the human ocular surface may serve as an additional entry gateway and infection hub for SARS-CoV-2. In this article, we review the ocular clinical presentations of COVID-19 and the features of the ocular surface that may underline the overall low ocular SARS-CoV-2 infection. We critically evaluate the studies performed in nonhuman primates, ex vivo organ culture ocular models, stem cell derived eye organoids and the differences in infection efficiency observed in different parts of human ocular surface epithelium. Finally, we highlight the additional work that needs to be carried out to understand the immune response of the ocular surface to SARS-CoV-2 infection, which can be translated into prophylactic treatments that may be applied to other organ systems.

Epidemiology, economic and humanistic burdens of Ocular Surface Chemical Injury: A narrative review.

Ocular surface chemical injury (OSCI) is a common type of ocular emergency that can potentially cause significant and permanent visual impairment. However, the global prevalence, demographic factors, socioeconomic burden, and psychological impact of OSCI have not been well investigated or reported. This review aims to provide a comprehensive overview of these aspects, highlight gaps in the literature, and advocate key strategies in reducing the incidence of OSCI. OSCI was responsible for 0.1-15% of all ocular emergency presentations, with an estimated incidence of 5.1-50 per 100,000 population-year. Young working adult men were the most at-risk group, though high rates of OSCI were also observed in young children in developed countries, especially from detergent pods. Low- and middle-income countries were noted to have higher proportions of assault-related and pediatric OSCI cases, often with more severe presentations. Direct and indirect costs for some hospitalized patients led to loss of all personal and household income after the injury. Emergency department costs in the United States were estimated at $106.7 million over four years and costs of treating long term complications such as glaucoma were estimated to be as high as $93,003 over five years. Significant negative impacts on visual and health-related quality of life and psychological well-being have been reported after injury, with higher rates of anxiety, depression, and psychological distress compared to the general population.

Practice patterns of corneal transplantation in Europe: first report by the European Cornea and Cell Transplantation Registry.

PURPOSE: To report practice patterns of corneal transplantation in Europe. SETTING: Corneal clinics in 10 European member states (MS), the United Kingdom, and Switzerland. DESIGN: Multinational registry study. METHODS: Corneal transplant procedures registered in the European Cornea and Cell Transplantation Registry were identified. Preoperative donor and recipient characteristics, indication and reason for transplantation, and surgical techniques were analyzed. RESULTS: A total of 12 913 corneal transplants were identified from 10 European Union MS, the United Kingdom, and Switzerland. Most countries were self-sufficient with regard to donor tissue. Fuchs endothelial corneal dystrophy was the most common indication (41%, n = 5325), followed by regraft (16%, n = 2108), pseudophakic bullous keratopathy (12%, n = 1594), and keratoconus (12%, n = 1506). Descemet stripping automated endothelial keratoplasty (DSAEK, 46%, n = 5918) was the most commonly performed technique, followed by penetrating keratoplasty (30%, n = 3886) and Descemet membrane endothelial keratoplasty (9%, n = 1838). Vision improvement was the main reason for corneal transplantation (90%, n = 11 591). Surgical technique and reason for transplantation differed between indications. CONCLUSIONS: This report provides the most comprehensive overview of corneal transplantation practice patterns in Europe to date. Fuchs endothelial dystrophy is the most common indication, vision improvement the leading reason, and DSAEK the predominant technique for corneal transplantation.

Use of biomaterials in corneal endothelial repair.

Human corneal endothelium (HCE) is a single layer of hexagonal cells that lines the posterior surface of the cornea. It forms the barrier that separates the aqueous humor from the rest of the corneal layers (stroma and epithelium layer). This layer plays a fundamental role in maintaining the hydration and transparency of the cornea, which in turn ensures a clear vision. In vivo, human corneal endothelial cells (HCECs) are generally believed to be nonproliferating. In many cases, due to their nonproliferative nature, any damage to these cells can lead to further issues with Descemet's membrane (DM), stroma and epithelium which may ultimately lead to hazy vision and blindness. Endothelial keratoplasties such as Descemet's stripping automated endothelial keratoplasty (DSAEK) and Descemet's membrane endothelial keratoplasty (DEK) are the standard surgeries routinely used to restore vision following endothelial failure. Basically, these two similar surgical techniques involve the replacement of the diseased endothelial layer in the center of the cornea by a healthy layer taken from a donor cornea. Globally, eye banks are facing an increased demand to provide corneas that have suitable features for transplantation. Consequently, it can be stated that there is a significant shortage of corneal grafting tissue; for every 70 corneas required, only 1 is available. Nowadays, eye banks face long waiting lists due to shortage of donors, seriously aggravated when compared with previous years, due to the global COVID-19 pandemic. Thus, there is an urgent need to find alternative and more sustainable sources for treating endothelial diseases, such as utilizing bioengineering to use of biomaterials as a remedy. The current review focuses on the use of biomaterials to repair the corneal endothelium. A range of biomaterials have been considered based on their promising results and outstanding features, including previous studies and their key findings in the context of each biomaterial.