Publications by authors named "Stephen Kaye"

227 Publications

Repeatability and Reproducibility of Macular Hole Size Measurements Using Optical Coherence Tomography.

J Clin Med 2021 Jun 29;10(13). Epub 2021 Jun 29.

Department of Eye and Vision Science, University of Liverpool, William Henry Duncan Building, 6 West Derby Street, Liverpool L7 8TX, UK.

The purpose of this study was to assess the repeatability and reproducibility of measuring the minimum linear diameter (MLD) of macular holes (MHs) using horizontal linear and radial scan modes in optical coherence tomography (OCT). Patients with concurrent sets of radial and horizontal linear OCT volume scans were included. The MLD was measured twice in both scan modes by six raters of three different experience levels (groups). Outcome measures were the reliability and repeatability of MLD measurements. Fifty patients were included. Mean MLD was 317.21(±170.63) µm in horizontal linear and 364.52 (±161.71) µm in radial mode, a difference of 47.31 (±26.48) µm ( < 0.001). In the radial scan mode, MLD was identified within 15° of the horizontal meridian in 27% and within 15° of the vertical meridian in 26.7%, with the remainder (46.3%) in oblique meridians. The intra-group coefficients of repeatability (CR) for horizontal linear mode were 23 µm, 33 µm and 45 µm, and for radial mode 25 µm, 44 µm and 57 µm for groups 1, 2 and 3, respectively. The inter-group CR, taking group 1 as reference standard for groups 2 and 3, were 74 µm and 71 µm for the linear mode, and 62 µm and 78 µm for radial mode. The radial mode provides good repeatability and reliability for measurement of MLD. In a majority of cases the MLD does not lie in the horizontal meridian and would be underestimated using a horizontal OCT mode.
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http://dx.doi.org/10.3390/jcm10132899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268292PMC
June 2021

Biological tissues and components, and synthetic substrates for conjunctival cell transplantation.

Ocul Surf 2021 Jun 11;22:15-26. Epub 2021 Jun 11.

Department of Eye and Vision Science, University of Liverpool, William Duncan Building, 6 West Derby Street, Liverpool, L7 8TX, UK. Electronic address:

The conjunctiva is the largest component of the ocular surface. It can be damaged by various pathological processes leading to scarring, loss of tissue and dysfunction. Depending on the amount of damage, restoration of function may require a conjunctival graft. Numerous studies have investigated biological and synthetic substrates in the search for optimal conditions for the ex vivo culture of conjunctival epithelial cells that can be used as tissue grafts for transplantation. These substrates have advantages and disadvantages that are specific to the characteristics of each material; the development of an improved material remains a priority. This review is the second of a two-part review in The Ocular Surface. In the first review, the structure and function of the conjunctiva was evaluated with a focus on the extracellular matrix and the basement membrane, and biological and mechanical characteristics of the ideal substrate with recommendations for further studies. In this review the types of biological and synthetic substrates used for conjunctival transplantation are discussed including substrates based on the extracellular matrix. .
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http://dx.doi.org/10.1016/j.jtos.2021.06.003DOI Listing
June 2021

Dual inhibition of complement component 5 and leukotriene B4 by topical rVA576 in atopic keratoconjunctivis: TRACKER phase 1 clinical trial results.

Orphanet J Rare Dis 2021 06 11;16(1):270. Epub 2021 Jun 11.

Moorfields Eye Hospital, 51 North Block, 5 Chicheley Street, London, SE1 7PJ, UK.

Purpose: To evaluate the safety and preliminary efficacy of topical rVA576, a dual inhibitor of complement component 5 (C5) and leukotriene B4 (LTB4), in patients with recalcitrant atopic keratoconjunctivitis (AKC) in the open label phase 1 TRACKER clinical trial.

Methods: Three patients diagnosed with moderate or severe AKC who had been on maximal topical treatment (antihistamines and ciclosporin) for at least three months prior to entry, and showed persistent symptoms and signs of inflammation, were recruited into the trial. Patients received rVA576 eye drops twice a day for 8 weeks. Patients were seen at baseline and weeks 1, 2, 4, 6 and 8. Safety data was recorded and a composite sum score of symptoms and signs was obtained. This score comprised symptoms such as itching, mucous discharge and photophobia, and conjunctival and corneal signs such as hyperemia, tarsal papillae, punctate keratitis and corneal neovascularization, all rated individually from 0 to 3 for a maximum score of 33.

Results: Two of the three patients completed the initial open label phase of the trial. The third patient was unable to attend appointments and terminated the study early at day 14. Topical rVA576 was well tolerated with no serious adverse events reported. There was an average improvement in overall clinical score of 53%, composed of an improvement in symptoms of 65% [63.64-66.67%] and signs of 40% [40-40.12%] by day 56.

Conclusions: In this open label phase 1 TRACKER trial, rVA576 eye drops were well tolerated and showed a response across signs and symptoms of active inflammation. This study is exploratory but supports topical rVA576 safety and shows promising efficacy for recalcitrant AKC. A phase 2 randomised control trial is currently underway.
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http://dx.doi.org/10.1186/s13023-021-01890-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196439PMC
June 2021

The conjunctival extracellular matrix, related disorders and development of substrates for conjunctival restoration.

Ocul Surf 2021 Jun 5. Epub 2021 Jun 5.

Department of Eye and Vision Science, University of Liverpool, William Duncan Building, 6 West Derby Street, Liverpool, L7 8TX, UK. Electronic address:

The conjunctiva can be damaged by numerous diseases with scarring, loss of tissue and dysfunction. Depending on extent of damage, restoration of function may require a conjunctival graft. A wide variety of biological and synthetic substrates have been tested in the search for optimal conditions for ex vivo culture of conjunctival epithelial cells as a route toward tissue grafts. Each substrate has specific advantages but also disadvantages related to their unique physical and biological characteristics, and identification and development of an improved substrate remains a priority. To achieve the goal of mimicking and restoring a biological material, requires information from the material. Specifically, extracellular matrix (ECM) derived from conjunctival tissue. Knowledge of the composition and structure of native ECM and identifying contributions of individual components to its function would enable using or mimicking those components to develop improved biological substrates. ECM is comprised of two components: basement membrane secreted predominantly by epithelial cells containing laminins and type IV collagens, which directly support epithelial and goblet cell adhesion differentiation and growth and, interstitial matrix secreted by fibroblasts in lamina propria, which provides mechanical and structural support. This review presents current knowledge on anatomy, composition of conjunctival ECM and related conjunctival disorders. Requirements of potential substrates for conjunctival tissue engineering and transplantation are discussed. Biological and synthetic substrates and their components are described in an accompanying review.
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http://dx.doi.org/10.1016/j.jtos.2021.05.011DOI Listing
June 2021

Expanding the supply of donor grafts.

Cornea 2021 May 27. Epub 2021 May 27.

St. Paul's Eye Unit, Royal Liverpool University Hospital, Liverpool, United Kingdom; University of Liverpool, Department of Eye and Vision Science, Liverpool, United Kingdom; Fondazione Banca Degli Occhi Del Veneto Onlus, Venice, Italy; and Institute of Ophthalmology, University College London, London, United Kingdom.

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http://dx.doi.org/10.1097/ICO.0000000000002777DOI Listing
May 2021

Predictive Association of Pre-Operative Defect Areas in the Outer Retinal Layers With Visual Acuity in Macular Hole Surgery.

Transl Vis Sci Technol 2021 04;10(4)

Royal Liverpool University Hospital, Liverpool, UK.

Purpose: The purpose of this study was to develop methods to model the external limiting membrane (ELM) and ellipsoid zone (EZ) within the elevated cuff surrounding a macular hole (MH) to determine if the predicted size of the defect in these layers after virtual flattening was associated with the actual postoperative defect and best-corrected visual acuity (BCVA).

Methods: Patients were included who had undergone successful MH surgery. The defects in the ELM and EZ after virtual flattening were modeled using in-house software. Main outcomes were postoperative defects in ELM and EZ at 2 months and BCVA at 12 months.

Results: Fifty-eight patients were included. BCVA improved from 0.87 (0.31) logMAR pre-operatively to 0.26 (0.21) at 12 months (P < 0.001). For both the ELM and EZ, the predicted virtually flattened pre-operative defects were associated with the actual postoperative defects at 2 months (R2 = 0.33, P < 0.01 and R2 = 0.50, P < 0.01, respectively). There was a significant association of BCVA at 12 months (adjusted R2 = 0.85) with the pre-operative modeled area of the defect in the ELM (P < 0.01) and to a lesser extent with the defect in the EZ (P < 0.01) and base of the MH (P < 0.01).

Conclusions: Virtually flattening of the pre-operative defect in the ELM provides important predictive information of visual acuity. Incorporation of tools into commercially available optical coherence tomography (OCT) devices to facilitate such measurements would provide the clinician with important prognostic information.

Translational Relevance: We have developed methodology that can potentially be used to predict the postoperative state of the outer retinal layers and the associated visual outcome in patients undergoing surgery for MH.
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http://dx.doi.org/10.1167/tvst.10.4.7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054630PMC
April 2021

Imaging of vascular abnormalities in ocular surface disease.

Surv Ophthalmol 2021 May 13. Epub 2021 May 13.

Corneal and External Eye Disease Service, The Royal Liverpool University Hospital, Liverpool, UK; Department of Eye and Vision Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK.

The vascular system of the ocular surface plays a central role in infectious, autoimmune, inflammatory, traumatic and neoplastic diseases. The development, application, and monitoring of treatments for vascular abnormalities depends on the in vivo analysis of the ocular surface vasculature. Until recently, ocular surface vascular imaging was confined to biomicroscopic and color photographic assessment, both limited by poor reproducibility and the inability to image lymphatic vasculature in vivo. The evolvement and clinical implementation of innovative imaging modalities including confocal microscopy, intravenous, and optical coherence tomography-based angiography now allows standardized quantitative and functional vascular assessment with potential applicability to automated analysis algorithms and diagnostics.
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http://dx.doi.org/10.1016/j.survophthal.2021.05.001DOI Listing
May 2021

Rebubbling rate in preloaded versus surgeon prepared DSAEK.

Eur J Ophthalmol 2021 May 4:11206721211014380. Epub 2021 May 4.

The Royal Liverpool University Hospital, Liverpool, UK.

Purpose: To compare the clinical outcomes of eye bank preloaded Descemet stripping automated endothelial keratoplasty (DSAEK) grafts and surgeon prepared.

Methods: In this retrospective study, the data were obtained from two groups (a) surgeon cut DSAEK where tissue was prepared by the surgeon immediately before surgery, and (b) preloaded DSAEK tissue shipped to the surgeon after preparation by the eye bank. Standard DSAEK preparations using Moria microkeratome with single pass method were performed. For the tissues prepared by the eye banks, they were preloaded in an iGlide device and shipped in transport media. Standard DSAEK surgery using bimanual pull-through technique was performed for all the grafts. Air was used as a tamponade. Main outcome measures included best corrected visual acuity (BCVA) and rebubbling rate.

Result: Out of 107 eyes of 101 patients that underwent DSAEK surgery, 33 tissues were prepared by the surgeon (sc-DSAEK), while 74 were prepared by the eye bank (pl-DSAEK). sc-DSAEK showed a rebubbling rate of 9.1%, compared to the 16.2% for the preloaded DSAEK ( = 0.11). There was no statistical difference in postoperative BCVA between the two groups. Logistic regression analysis showed no association between detachment rate and cataract surgery, graft preparation method, graft diameter and reason for graft.

Conclusion: Preloaded grafts have similar rebubbling rate and visual acuity achieved compared with surgeon prepared grafts.
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http://dx.doi.org/10.1177/11206721211014380DOI Listing
May 2021

Use of dried amniotic membrane with glue to manage a corneal perforation.

Eye (Lond) 2021 May 3. Epub 2021 May 3.

The Royal Liverpool University Hospital, Liverpool, UK.

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http://dx.doi.org/10.1038/s41433-021-01558-2DOI Listing
May 2021

Functional and morphological outcomes of the inverted internal limiting membrane flap technique in small and medium sized macular holes <400µm.

Retina 2021 Feb 25. Epub 2021 Feb 25.

Hospital rechts der Isar, Technical University of Munich (TUM), Ismaninger Str. 22, 81675 Munich, Germany Royal Liverpool University Hospital, Prescot Street, Liverpool L1 8XP, United Kingdom.

Purpose: To assess the effect of an internal limiting membrane (ILM) flap (IF) in MH surgery on best-corrected visual acuity (BCVA) and integrity of the ellipsoid zone (EZ) and external limiting membrane (ELM).

Methods: Patients were included who had successful surgery for MH <400µm with or without an IF. Main outcome measures were BCVA and restoration of the ELM and EZ at 12 months.

Results: 60 patients were included, 36 with conventional peeling and 24 with an IF. BCVA improved from 0.74 (±0.30) logMAR (20/110 Snellen) to 0.26 (±0.20) (20/36 Snellen) in patients without and from 0.77 (±0.32) logMAR (20/118 Snellen) to 0.18 (±0.12) (20/30 Snellen) in patients with an IF, respectively. There was no difference in the integrity of the EZ and ELM in patients with or without an IF at either 3 (p=0.58, p=0.20), 6 (p=0.81, p=0.10) or 12 months (p=0.60, p=0.20) or in BCVA at 3 (p=0.24), 6 (p=0.18) and 12 months (p=0.11). In the multivariable model, only pre-operative BCVA (p<0.01), EZ integrity (p=0.001) and age (p<0.01) were associated with post-operative BCVA.

Conclusions: In patients undergoing surgery for MH <400µm the use of an IF did not affect BCVA or the integrity of the EZ and ELM.
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http://dx.doi.org/10.1097/IAE.0000000000003160DOI Listing
February 2021

Intrastromal voriconazole for refractory infectious crystalline keratopathy associated with Candida pararugosa.

Can J Ophthalmol 2021 Mar 18. Epub 2021 Mar 18.

St Paul's Eye Unit, Royal Liverpool University Hospital, Liverpool, United Kingdom.

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http://dx.doi.org/10.1016/j.jcjo.2021.02.023DOI Listing
March 2021

Impact of COVID-19 on keratoconus patients waiting for corneal cross linking.

Eur J Ophthalmol 2021 Mar 15:11206721211001315. Epub 2021 Mar 15.

Department of Ophthalmology, Royal Liverpool University Hospital, Liverpool, UK.

Purpose: Royal College of Ophthalmologist recent guidance recommended delaying cross-linking services during the COVID-19 pandemic. This study investigates the effects of such delays in the delivery of cross-linking services in patients with keratoconus progression.

Methods: Retrospective observational study of 46 patients with keratoconus progression, whose cross-linking was delayed due to the COVID-19 pandemic. Demographic and clinical details were obtained from assessments on the day of listing, and subsequent review on the day of the procedure. Topographic indices included keratometry of the posterior and anterior corneal surface, maximum keratometry (), thinnest corneal thickness, ABCD progression and progression based on standard criteria recommendations (1.5 D & 20 microns thinning).

Results: A total of 46 eyes were analysed with an average time between being listed for CXL and having the procedure done was 182 ± 65 days. The delay due to COVID-19 was of 3 months. In this time period they had a significant worsening of all keratometric indices and lost almost one line of visual acuity (0.19 ± 0.19 to 0.26 ± 0.18 LogMAR, : 0.03). Thirty two eyes (70%) demonstrated progression in accordance with the ABCD progression criteria, while 18 eyes (39%) showed either an increase in of more than 1.5D or a thinning in corneal thickness of at least 20 μm.

Conclusions: The treatment delay for the keratoconus patients caused further progression and vision worsening. We recommend that corneal collagen crosslinking needs to be considered as a high priority intervention.
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http://dx.doi.org/10.1177/11206721211001315DOI Listing
March 2021

Keratitis: Incidence, Pathophysiology, Risk Factors and Novel Strategies for Treatment.

J Clin Med 2021 Feb 13;10(4). Epub 2021 Feb 13.

Department of Eye and Vision Science, University of Liverpool, Liverpool L7 8TX, UK.

Bacterial keratitis is a devastating condition that can rapidly progress to serious complications if not treated promptly. Certain causative microorganisms such as and are notorious for their resistance to antibiotics. Resistant bacterial keratitis results in poorer outcomes such as scarring and the need for surgical intervention. Thorough understanding of the causative pathogen and its virulence factors is vital for the discovery of novel treatments to avoid further antibiotic resistance. While much has been previously reported on , has been less extensively studied. This review aims to give a brief overview of epidemiology, pathophysiology and clinical characteristics as well as summarise the current evidence for potential novel therapies.
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http://dx.doi.org/10.3390/jcm10040758DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918096PMC
February 2021

Biomaterials for corneal endothelial cell culture and tissue engineering.

J Tissue Eng 2021 Jan-Dec;12:2041731421990536. Epub 2021 Feb 16.

Department of Eye and Vision Science, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK.

The corneal endothelium is the posterior monolayer of cells that are responsible for maintaining overall transparency of the avascular corneal tissue via pump function. These cells are non-regenerative in vivo and therefore, approximately 40% of corneal transplants undertaken worldwide are a result of damage or dysfunction of endothelial cells. The number of available corneal donor tissues is limited worldwide, hence, cultivation of human corneal endothelial cells (hCECs) in vitro has been attempted in order to produce tissue engineered corneal endothelial grafts. Researchers have attempted to recreate the current gold standard treatment of replacing the endothelial layer with accompanying Descemet's membrane or a small portion of stroma as support with tissue engineering strategies using various substrates of both biologically derived and synthetic origin. Here we review the potential biomaterials that are currently in development to support the transplantation of a cultured monolayer of hCECs.
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http://dx.doi.org/10.1177/2041731421990536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894589PMC
February 2021

Indocyanine Green Angiographic Assessment of Conjunctival Melanocytic Disorders.

Cornea 2021 Feb 15. Epub 2021 Feb 15.

Department Ophthalmology, Medical University of Innsbruck, Austria; and Department of Eye and Vision Science, University of Liverpool, Liverpool, United Kingdom.

Purpose: To investigate whether transvascular indocyanine green (ICG) dye leakage is associated with conjunctival malignancy.

Methods: This is a prospective interventional study. Patients presenting with circumscribed conjunctival melanocytic disorders (CMDs) were included and examined using color photography, anterior segment optical coherence tomography to measure lesion size, and fluorescein and ICG angiography to measure vascular pattern and leakage. Time to vascular leakage was measured by 2 independent observers. Lesions were characterized as benign or malignant based on histopathological features.

Results: Thirty patients with CMD were included: 22 lesions were benign (conjunctival nevus, n = 20; conjunctival melanocytic intraepithelial neoplasia without atypia, n = 2) and 8 were malignant (in situ conjunctival melanoma n = 2; invasive conjunctival melanoma, n = 6). Malignant lesions had larger mean maximal diameters (11.0 ± 4.5 vs. 4.2 ± 2.5 mm, P = 0.003) and more frequently showed intrinsic tumor vasculature (8 of 8 vs. 10 of 22, P = 0.007). The mean time to ICG leakage was 350.9 ± 165.9 seconds in benign and 59.6 ± 22.1 seconds (P = 0.002) in malignant lesions and was inversely correlated with lesion size and thickness.

Conclusions: Time to angiographic ICG dye leakage is significantly shorter in malignant versus benign CMD.
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http://dx.doi.org/10.1097/ICO.0000000000002681DOI Listing
February 2021

A pipeline to evaluate inhibitors of the Pseudomonas aeruginosa exotoxin U.

Biochem J 2021 02;478(3):647-668

Department of Eye and Vision Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, U.K.

Pseudomonas aeruginosa has recently been highlighted by the World Health Organisation (WHO) as a major threat with high priority for the development of new therapies. In severe P. aeruginosa infections, the phospholipase activity of the type 3 secretion system toxin, ExoU, induces lysis of target host cells and results in the poorest clinical outcomes. We have developed an integrated pipeline to evaluate small molecule inhibitors of ExoU in vitro and in cultured cell models, including a disease-relevant corneal epithelial (HCE-T) scratch and infection model using florescence microscopy and cell viability assays. Compounds Pseudolipasin A, compound A and compound B were effective in vitro inhibitors of ExoU and mitigated P. aeruginosa ExoU-dependent cytotoxicity after infection of HCE-T cells at concentrations as low as 0.5 µM. Addition of the antimicrobial moxifloxacin controlled bacterial load, allowing these assays to be extended from 6 h to 24 h. P. aeruginosa remained cytotoxic to HCE-T cells with moxifloxacin, present at the minimal inhibitory concentration for 24 h, but, when used in combination with either Pseudolipasin A, compound A or compound B, a greater amount of viable cells and scratch healing were observed. Thus, our pipeline provides evidence that ExoU inhibitors could be used in combination with certain antimicrobials as a novel means to treat infections due to ExoU producing P. aeruginosa, as well as the means to identify more potent ExoU inhibitors for future therapeutics.
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http://dx.doi.org/10.1042/BCJ20200780DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886320PMC
February 2021

Tomographic and aberrometric assessment of first-time diagnosed paediatric keratoconus based on age ranges: a multicentre study.

Acta Ophthalmol 2020 Dec 30. Epub 2020 Dec 30.

Department of Ophthalmology, Regional University Hospital of Malaga, Malaga, Spain.

Purpose: To describe paediatric keratoconus (KC) patients by tomographic and aberrometric characteristics at first diagnosis, in a multicentre study.

Methods: We included 278 eyes from 139 paediatric patients, with a first tomographic diagnosis (Pentacam ) of KC prior to 18 years old. KC classification was based on the KC Index (≥ 1.07) and Topographic Keratoconus Classification (TKC ≥ 1). Patients were divided based on age ranges (14 and under and over 14 years) and gender. Statistical analysis was performed with SPSS statistics 25.0. ANOVA factor was carried out comparing to compare groups.

Results: 278 eyes were screened, and 230 eyes were diagnosed with paediatric KC. Mean age was 15.48 ± 2.33 (6 to 18) years. We found differences in terms of TKC (2.08 ± 0.89 and 2.38 ± 0.82, p < 0.05) and spherical aberration (-0.71 ± 0.97 and -1.07 ± 1.36, p < 0.05) among the 14 years old or under and above 14 years old groups, respectively. Overall, female paediatric KC patients presented a more severe TKC, Belin Ambrosio Display, maximum keratometry, asphericity and primary and secondary coma aberrations compared to male KC patients. We observed a correlation between CDVA and asphericity (r = 0.71, p < 0.01), as well as between CDVA and spherical aberration (r = 0.69, p < 0.01).

Conclusion: Our findings revealed that the debut of KC is usually in a moderate to advanced stage in the paediatric population at first diagnosis, particularly in female patients. Corneal tomography should be systematically performed in children with recent onset of corneal astigmatism.
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http://dx.doi.org/10.1111/aos.14715DOI Listing
December 2020

Changes in pupillometry associated with dissipated energy during phacoemulsification.

Eur J Ophthalmol 2020 Dec 29:1120672120984377. Epub 2020 Dec 29.

St Paul's Eye Unit, Royal Liverpool University Hospital, Liverpool, UK.

Purpose: To investigate the effect of ultrasound level during phacoemulsification on pupil dynamics.

Methods: Comparative retrospective study on patients who underwent routine cataract surgery at the Royal Liverpool University Hospital. Clinical parameters, anterior chamber measurements, axial length, surgeon grade, time of surgery, level of ultrasound used (cumulative dissipated energy, CDE), intra- and post-operative complications were collected. Pupil diameters were collected before and 4 ± 1 weeks after surgery in static scotopic, mesopic, photopic pupil conditions. Also, pupil dynamic measurements after luminous stimulus were recorded. Changes in static pupil diameters, relative dilation at 3.5 s after luminous stimulus, and time to reach 75% and 95% of maximum dilation were measured.

Results: Forty-eight eyes of 24 patients (13 males) were included with a mean age of 73.1 ± 14.6 years. Mean CDE value was 18.11 ± 10.56. Mean scotopic pupil diameters decreased by 0.24 ± 0.48 mm ( = 0.021) in the operated eye. Significant correlation was found between reduction in scotopic pupil diameter and CDE ( = 0.05). A generalized linear model confirmed that the level of CDE was significantly associated with reduction in scotopic pupil diameter ( = 0.026). Patients who underwent surgeries with lower CDE (0 < CDE ⩽ 10 and 10 < CDE ⩽ 20) did not experience significant changes in scotopic pupil diameter after surgery ( = 0.28 and  = 0.79, respectively) as opposed to those with higher CDE (CDE > 20;  = 0.03).

Conclusion: Phacoemulsification cataract surgery and the cumulative dissipated energy may be associated with changes in pupil behaviour.
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http://dx.doi.org/10.1177/1120672120984377DOI Listing
December 2020

16S Ribosomal RNA PCR Versus Conventional Diagnostic Culture in the Investigation of Suspected Bacterial Keratitis.

Transl Vis Sci Technol 2020 12 1;9(13). Epub 2020 Dec 1.

Department of Eye and Vision Sciences, University of Liverpool, Liverpool, UK.

Purpose: The purpose of this study was to compare conventional diagnostic culture (CDC) to 16S ribosomal RNA polymerase chain reaction (PCR) analysis for diagnosing bacterial keratitis.

Methods: Samples collected from 100 consecutive patients presenting to the Royal Liverpool University Hospital with bacterial keratitis were processed using CDC and 16S PCR analysis.

Results: The overall detection rate using both methods was 36%. Of these, 72.2% (26/36) were detected by PCR and 63.9% (23/36) isolated by CDC ( = 0.62). Using a combination of both PCR and CDC increased the detection rate for pathogenic bacteria by 13% compared to using CDC alone ( = 0.04). In CDC negative samples, 16S PCR identified more pathogens than CDC in 16S PCR negative samples. Neither order of sample collection nor prior antimicrobial use affected the detection rate.

Conclusions: 16S rRNA gene PCR performed in addition to CDC on corneal samples from patients with clinically suspected bacterial keratitis led to additional pathogen detection.

Translational Relevance: 16S rRNA gene PCR should be developed to become an additional part of clinical service for patients with bacterial keratitis rather than used in isolation.
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http://dx.doi.org/10.1167/tvst.9.13.2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7718820PMC
December 2020

DSAEK and STC-6 Needle.

Cornea 2021 03;40(3):e5

Department of Corneal Diseases, St. Paul's Eye Unit, Royal Liverpool University Hospital, Liverpool, UK.

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http://dx.doi.org/10.1097/ICO.0000000000002600DOI Listing
March 2021

Eye bank versus surgeon prepared DMEK tissues: influence on adhesion and re-bubbling rate.

Br J Ophthalmol 2020 Oct 30. Epub 2020 Oct 30.

UCL, London, UK.

Aim: To investigate the difference in adhesion and rebubbling rate between eye bank and surgeon prepared Descemet membrane endothelial keratoplasty (DMEK) tissues.

Methods: Laboratory and clinical retrospective comparative interventional case series. Research corneal tissues were obtained for laboratory investigation. The clinical study involved patients with endothelial dysfunction who underwent DMEK surgery and tamponade with air. Tissues were stripped using a standard DMEK stripping technique (SCUBA) and shipped as prestripped or loaded in a 2.2 intra-ocular lens cartridge with endothelium facing inwards (preloaded) before transporting from the eye bank to the surgeon. For surgeon prepared tissues, all the grafts were stripped in the theatre and transplanted or stripped in the laboratory and tested immediately. Adhesion force and elastic modulus were measured in the centre and mid-periphery in a laboratory ex vivo investigation using atomic force microscopy, while rebubbling rates were recorded in the clinical study.

Results: There was no difference in endothelial cell viability between surgeon or eye bank prepared tissue. Surgeon-stripped DMEK grafts in the laboratory investigation showed significantly higher elastic modulus and adhesion force compared to prestripped and preloaded tissues (p<0.0001). In the clinical data, rebubbling rates of 48%, 40% and 15% were observed in preloaded, prestripped and surgeon-stripped DMEK grafts, respectively. Rebubbling rates were significantly associated with combined cataract surgery (p=0.009) and with time from harvesting the graft to the surgery (p=0.02).

Conclusions: Decreased adhesion forces and elastic modulus in eye bank prepared tissues may contribute to increased rebubbling rates.
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http://dx.doi.org/10.1136/bjophthalmol-2020-317608DOI Listing
October 2020

Recurrent microbial keratitis and endogenous site Staphylococcus aureus colonisation.

Sci Rep 2020 10 29;10(1):18559. Epub 2020 Oct 29.

Department of Eye and Vision Sciences, University of Liverpool, 6 West Derby Street, Liverpool, L7 8TX, UK.

This study investigated Staphylococcus aureus carriage in patients with microbial keratitis (MK). 215 patients with MK, 60 healthy controls and 35 patients with rheumatoid arthritis (RA) were included. Corneal scrapes were collected from patients with MK. Conjunctival, nasal and throat swabs were collected from the non-MK groups on a single occasion and from the MK group at presentation and then at 6 and 12 weeks. Samples were processed using conventional diagnostic culture. 68 (31.6%) episodes of clinically suspected MK were classed as recurrent. Patients with recurrent MK had a higher isolation rate of S. aureus from their cornea than those with a single episode (p < 0.01) and a higher isolation rate of S. aureus from their conjunctiva compared to control participants, 20.6% (14/68) versus 3% (5/60) respectively (p = 0.01). Significantly more patients with recurrent MK (12/68, 17.6%) were found to have S. aureus isolated from both their conjunctiva and nose than those with a single episode of MK (7/147, 4.8% p = 0.002) and compared to patients in the control group (3/60, 5.0% p = 0.03). The results indicate that patients with recurrent MK have higher rates of carriage of S. aureus suggesting endogenous site colonisation as a possible source of recurrent infection.
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http://dx.doi.org/10.1038/s41598-020-75821-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596706PMC
October 2020

Persistent loss of marginal corneal arcades after chemical injury.

Indian J Ophthalmol 2020 Nov;68(11):2543-2544

Department of Ophthalmology, Royal Liverpool University Hospital; Department of Eye and Vision Science, University of Liverpool, Liverpool, United Kingdom.

Changes in the limbal microvasculature following a chemical eye injury are essential for prognosis and management. At the slit lamp, it can be difficult to assess, here using fluorescein and indocyanine green angiography we show that anterior segment angiography may be informative to assess objectively the limbal microvascular changes over the follow-up period.
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http://dx.doi.org/10.4103/ijo.IJO_2056_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774169PMC
November 2020

Clinical outcomes of pre-loaded ultra-thin DSAEK and pre-loaded DMEK.

BMJ Open Ophthalmol 2020 16;5(1):e000546. Epub 2020 Oct 16.

Ophthalmology, Royal Liverpool University Hospital, Liverpool, UK.

Objective: To compare clinical outcomes and complications between pre-loaded ultra-thin Descemet stripping automated endothelialkeratoplasty (pl-UT-DSAEK) and pre-loaded Descemet membrane endothelial keratoplasty (pl-DMEK).

Methods And Analysis: Comparative study in patients with endothelial dysfunction associated with Fuchs endothelial corneal dystrophy and pseudophakic bullous keratopathy who underwent pl-UT-DSAEK or pl-DMEK transplants. For both groups, the tissues were pre-loaded at the Fondazione Banca degli Occhi del Veneto (Venice, Italy) and shipped to The Royal Liverpool University Hospital (Liverpool, UK). Best corrected visual acuity (BCVA) and re-bubbling rates were the main outcome measures.

Results: 56 eyes of 56 patients were included. 31 received pl-UT-DSAEK and 25 received pl-DMEK. At 12 months, BCVA (LogMAR) was significantly better for pl-DMEK (0.17±0.20 LogMAR) compared with pl-UT-DSAEK (0.37±0.37 LogMAR, p<0.01). The percentage of people that achieved ≥20/30 was significantly higher in the pl-DMEK group. The rate of re-bubbling, however, was significantly higher for pl-DMEK (44.0%) than for Pl-UT-DSAEK (12.9%), p<0.01.

Conclusion: Pl-DMEK offers better BCVA than pl-UT-DSAEK. The higher re-bubbling rate associated with pre-loaded DMEK is of concern.
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http://dx.doi.org/10.1136/bmjophth-2020-000546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7569929PMC
October 2020

En-face analysis of the human limbal lymphatic vasculature.

Exp Eye Res 2020 12 28;201:108278. Epub 2020 Sep 28.

Department Ophthalmology, Medical University of Innsbruck, Austria. Electronic address:

Purpose: To describe the location and morphometric characteristics of the human limbal lymphatic vasculature and its relation to the marginal corneal vascular arcades (MCA).

Methods: Ex vivo confocal microscopic (CM) imaging and immunofluorescence double staining for CD-31 and D2-40 of histological en-face sections using 12 preserved human cadaveric corneoscleral discs were performed, followed by a semi-automated morphometric analysis of the two-dimensional vascular network architecture.

Results: Ex vivo CM confirmed the presence of 2 distinct vascular networks. The haematic limbal vascular complex (HLVC) extended further into the cornea, forming typical MCAs. The lymphatic limbal vascular complex (LLVC) was peripheral from the termination of Bowman's layer and was also found to be peripheral to and deeper than the HLVC. LLVC and HLVC were significantly different with respect to vessel diameter, segment length and wall thickness.

Conclusion: The lymphatic vasculature of the human corneoscleral limbal region displays specific morphometric features that allow its differentiation from haematic vessels using CM.
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http://dx.doi.org/10.1016/j.exer.2020.108278DOI Listing
December 2020

Observation of angiographic dye leakage in ocular surface squamous neoplasia.

Am J Ophthalmol Case Rep 2020 Dec 8;20:100912. Epub 2020 Sep 8.

St. Paul's Eye Unit, Royal Broadgreen University Hospital, Liverpool, UK.

Purpose: The clinical diagnosis of ocular surface squamous neoplasia is challenging, mostly requiring excisional biopsy. Human tumor angiogenesis is characterized by abnormal vessel architecture and transvascular hyperpermeability. This case report describes features of fluorescein and indocyanine green angiography in a case of conjunctival intraepithelial neoplasia.

Observations: Color photography, optical coherence tomography, fluorescein and indocyanine green angiography were performed in a patient with suspected conjunctival intraepithelial neoplasia before excisional biopsy and histologic confirmation of clinical diagnosis. Fluorescein dye showed extensive early extravascular dye leakage within the limits of the lesion. Indocyanine green dye displayed corneal terminal vessel bulbs with early leakage after 70 seconds and showed diffuse intralesional dye leakage after 7 minutes.

Conclusions: Increased fluorescein and early indocyanine green dye leakage can be used to confirm active angiogenesis already in early stages of dysplastic ocular surface squamous neoplasia. Late leakage of indocyanine green dye may be due to chronic transvascular hyperpermeability within intrinsic tumor vessels. The leakage behaviour of intravenous dyes has the potential to serve as a diagnostic indicator of active growth in dysplastic ocular surface neoplastic lesions.
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http://dx.doi.org/10.1016/j.ajoc.2020.100912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7495007PMC
December 2020

Eye Banking: One Cornea for Multiple Recipients.

Cornea 2020 Dec;39(12):1599-1603

St. Paul's Eye Unit, Royal Liverpool University Hospital, Liverpool, United Kingdom.

Purpose: Corneal transplantation is the most frequently performed transplant procedure. In much of the world, the demand for donor tissue heavily outstrips supply. With developments within lamellar corneal graft surgery, the use of split corneal donor tissue to increase donor tissue supply seems a pragmatic solution to reduce the supply and demand mismatch. This is especially important with tissue supply expected to be affected by the COVID-19 pandemic.

Methods: A literature review of techniques was performed, enabling multiple transplants to be derived from a single donor and simulation of a model to quantify the number of corneas potentially saved.

Results: Studies on splitting corneal donor tissue have demonstrated that up to 5 recipients may benefit from 1 donor scleral button. The impact of splitting donor tissue may provide a saving of up to 25.3% of donor graft tissue.

Conclusions: Splitting and preparing the donor tissue within an eye bank will improve tissue validation and donor tissue availability and may increase surgeon efficiency.
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http://dx.doi.org/10.1097/ICO.0000000000002476DOI Listing
December 2020

BMJ Open Ophthalmology.

Authors:
Stephen B Kaye

BMJ Open Ophthalmol 2020 1;5(1):e000530. Epub 2020 Sep 1.

Department of Eye and Vision Science, University of Liverpool, Liverpool, UK.

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http://dx.doi.org/10.1136/bmjophth-2020-000530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7467524PMC
September 2020

Bilateral Keratoconus Progression: Immediate Versus Delayed Sequential Bilateral Corneal Cross-linking.

J Refract Surg 2020 Aug;36(8):552-556

Purpose: To compare immediate sequential bilateral corneal cross-linking (CXL), wherein both eyes are treated on the same day, to delayed sequential bilateral CXL, where each eye is treated on different days for bilateral progressive keratoconus.

Methods: This was a retrospective case note review of all patients who underwent sequential CXL or delayed CXL for keratoconus at Royal Liverpool University Hospital, United Kingdom. Parameters assessed were the change in maximum keratometry and minimum central corneal thickness on corneal tomography scan, corrected distance visual acuity, and cost estimates of treatment.

Results: A total of 38 patients (31 men and 7 women) with keratoconus with a mean age of 25.3 ± 7.0 years were included. Twenty patients received sequential CXL and 18 received delayed CXL treatment. In both the sequential CXL and delayed CXL groups, the treated eye(s) showed no evidence of progression after the corneal CXL treatment at last follow-up visit after 358 ± 158 days for sequential CXL and 451 ± 205 days for delayed CXL. There were no complications from the treatment in either group. In the delayed CXL group, the mean time interval between the two CXL procedures was 146 ± 129 days. Five of 18 patients (27%) showed progression of keratoconus in their second eye during the waiting time. Economical evaluation showed that four visits were saved for each sequential CXL treatment compared to delayed CXL.

Conclusions: Delayed CXL carries a risk of progression in the second eye and is associated with a higher economic burden. [J Refract Surg. 2020;36(8):552-556.].
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http://dx.doi.org/10.3928/1081597X-20200629-01DOI Listing
August 2020

Antimicrobial Activity of Poly-epsilon-lysine Peptide Hydrogels Against Pseudomonas aeruginosa.

Invest Ophthalmol Vis Sci 2020 08;61(10):18

Department of Eye and Vision Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, United Kingdom.

Purpose: To determine the antimicrobial activity of poly-epsilon-lysine (pɛK) functionalization of hydrogels against Pseudomonas aeruginosa.

Methods: Antimicrobial activities of pɛK and pɛK+ hydrogels were tested against both keratitis and a laboratory strain of Paeruginosa at a range of inocula sizes, over 4 and 24 hours. The number of viable CFU on pɛK and pɛK+ hydrogels or commercial contact lenses (CL) was investigated. Ex vivo porcine corneas were inoculated with Paeruginosa PAO1 (103 CFU) and incubated with pɛK+ hydrogels or commercial hydrogel CL for 24 hours and the effects of infection determined.

Results: PɛK+ hydrogels showed log reductions in viable CFU compared with pɛK hydrogels for all Paeruginosa strains, depending on inocula sizes and incubation time. After 24 hours pɛK+ hydrogels showed >5 and >7.5 log reduction in CFU compared with commercial hydrogel CL at 103 and 106 CFU, respectively. In an ex vivo porcine corneal infection model, pɛK+ hydrogels led to a significant decrease in viable PAO1 CFU and histologic analysis indicated a decreased infiltration of PAO1 into the stroma.

Conclusions: PɛK+ hydrogels demonstrated enhanced antimicrobial activity versus nonfunctionalized pɛK hydrogels against clinically relevant Paeruginosa strains. PɛK+ hydrogels have the potential to be used as a bandage CL with innate antimicrobial characteristics to minimize the risk of microbial keratitis.
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http://dx.doi.org/10.1167/iovs.61.10.18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7441358PMC
August 2020
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