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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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Aims: To investigate the relative risk of pretransplant corneal vascularisation on rate of rejection and graft failure within 5 years of surgery when categorised by indication for transplantation.We analysed all adults recorded in the UK transplant registry who had a first cornea transplant for keratoconus (KC), pseudophakic bullous keratopathy (PBK) or previous infection (viral/bacterial/fungal/protozoan) between 1999 and 2017. We analysed the number of quadrants of the recipient cornea vascularised before transplant and type of vascularisation, the interval post-transplant to rejection, if any, and the outcome at 5 years post-transplant. Risk factors for rejection and transplant failure were modelled by multivariable risk-adjusted Cox regression., Results: Corneal vascularisation was recorded in 10%, 25% and 67% of patients with KC, PBK and infection, respectively. Individuals with PBK had an increased hazard of transplant rejection only when there were more than two quadrants of vascularisation (HR 1.5, p=0.004) when either superficial and/or deep vascularisation was present (HR 1.3 and 1.4, respectively, p=0.004). Individuals who had a transplant for previous infection had an increased hazard of rejection with four quadrants of vascularisation (HR 1.6, p=0.003). There was no risk-adjusted increase in transplant failure associated with vascularisation in any group. There was weak evidence of reduction in risk of rejection and/or failure associated with lamellar compared with penetrating transplantation in KC and PBK in vascularised recipient corneas., Conclusion: Vascularisation is a risk factor for corneal allograft rejection within 5 years. The indication for transplantation has a clinically significant effect on the magnitude of this risk., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/aims: Descemet membrane endothelial keratoplasty (DMEK) preparation is technically demanding and is a limiting factor for uptake of this kind of surgery. Supply methods that simplify the procedure for surgeons are key to increasing uptake. This study compares two different shipping protocols for DMEK., Methods: An 8.5 mm DMEK graft was punched, marked and loaded for transportation in two different conditions: (A) endothelium trifolded inwards in organ culture conditions (n=7) and (B) endothelium rolled outwards in hypothermic conditions (n=7). Tissues were shipped from Italy to the UK, then analysed for orientation, endothelial cell density, denuded areas, cell mortality, triple viability staining (Hoechst/ethidium homodimer/calcein AM (HEC)), immunolocalisation of ZO-1 and Na/K-ATPase proteins, visualisation of actin filaments using phalloidin and histological analysis using H&E on paraffin-embedded sections., Results: All tissues clearly showed the mark used for graft orientation. After shipping in condition A, there was an increase in cell mortality of 8.1% and in denuded areas of 22.4%, whereas for condition B there was an increase in cell mortality of 14.2% and in denuded areas of 34.3% after shipping. HEC staining revealed areas of viable cells and apoptotic cells, with large denuded areas found in the periphery for condition B and within folds for condition A., Conclusions: Prestripped preloaded DMEK grafts retained sufficient viable cells for transplantation, with condition A (endothelium-in) offering the advantage of greater flexibility of use due to a longer shelf-life. HEC analysis provides further detailed information as to the status of DMEK grafts and should be used in future similar studies., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Aims: To investigate the role of high-resolution anterior segment optical coherence tomography (HR-ASOCT) in the assessment of pterygia., Methods: Single centre cross-sectional study. Patients with primary pterygium and/or pingueculae were included. Clinical assessment included HR-ASOCT, colour photography, keratometry followed by histology. Associations were tested between HR-ASOCT features of the pterygium and the degree of corneal scarring and elastotic degeneration, astigmatism and best-corrected visual acuity., Results: 29 eyes of 26 patients with pterygium and 6 patients with pinguecula were included. Apical anterior stromal scarring was found in 23 cases (79.3%) reaching a mean depth of 68.8±21.7 µm (minimum: 33 µm, maximum: 126 µm). Increased stromal scarring and subepithelial elastotic degenerative tissue was significantly associated with HR-ASOCT features of flat bridging of the corneoscleral transition zone (p<0.01) reduced thickness of the pterygium head (p=0.01), and a greater degree of corneal astigmatism (p=0.04)., Conclusions: HR-ASOCT is a useful tool for the assessment and monitoring of pterygia in clinical practice. Features associated with increased stromal scarring and astigmatism are reduced thickness of the head of the pterygium and flat bridging of the corneoscleral transition zone., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Purpose: To determine if donor age and preoperative endothelial cell density (ECD) affect corneal endothelial failure following penetrating keratoplasty (PK)., Methods: Preoperative and postoperative data for PKs performed in the UK between April 1999 and March 2012 were analysed. Donor age was split into three groups (0-60, 61-75 and >75 years) and donor ECD was split into three groups (≤2400, 2401-2600 and >2600 cells/mm 2 ). Cox proportional hazards regression was used to determine whether the selected subgroups of donor age and donor ECD have an impact on endothelial failure and a systematic analysis of the interaction between donor ECD and donor age was conducted. The analysis was stratified for primary corneal diagnosis (Fuchs endothelial dystrophy (FED), pseudophakic bullous keratopathy (PBK) and other) and corrected for potentially confounding factors (human leukocyte antigen matching, donor trephine diameter, deep vascularisation, the occurrence of reversible rejection episodes and receipt of systemic antiviral medication, long-term steroids or other immunosuppressive agents)., Results: A total of 9415 patients, from the National Health Service Blood and Transplant UK Transplant Registry, who received their first PK for visual reasons were included in this study. The overall 5-year graft survival rate due to endothelial failure was 89%. Survival rates in recipients with FED, PBK and 'all other indications' were 95%, 83% and 89%, respectively. Our analysis shows that donor ECD did not affect outcome following corneal graft within the preselected categories, irrespective of diagnosis and after allowing for any potential confounding factors. Furthermore, HRs for each level of donor ECD, relative to >2600 cells/mm 2 , for each combination of age group and indication, were not statistically significant., Conclusions: We were unable to detect a significant effect of donor age, up to 90 years, and preoperative donor ECD, above the lower limit of 2200 cells/mm 2 , on endothelial failure at 5 years following PK., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Purpose: To evaluate graft size on outcome following Descemet stripping automated endothelial keratoplasty (DSAEK) METHODS: Consecutive patients who had undergone a DSAEK for Fuchs endothelial dystrophy (FED) and pseudophakic bullous keratopathy (PBK) with at least 1 year of follow-up. Patients were divided into three groups according to the size of the donor trephine: <9, 9 and 9.5 mm. Main outcomes were postoperative best corrected visual acuity (BCVA) and graft failure. Grafts were prepared using an automated microkeratome. For larger grafts (≥9 mm), a manual dissection of the residual peripheral ring of anterior lamella was performed before trephination. Donor age, endothelial cell density (ECD) and postmortem times; recipient details including risk factors, comorbidity, surgical complications and postoperative BCVA and graft survival were analysed., Results: Of 174 patients, 131 were included: 84 (64%) with FED and 47 (36%) with PBK. Mean preoperative and postoperative BCVA were 1.01±0.76 and 0.2±0.2 logMAR, respectively, at 12 months with 80.5% achieving 20/40 or better. Postoperative BCVA was significantly associated with ECD (p=0.005), PBK or FED (p=0.004), risk factors (p=0.007) and comorbidity (p=0.016). Eleven patients (8.40%) experienced endothelial graft failure; 17.86% for <9 mm, 7.69% for 9 mm and 3.84% for 9.5 mm trephine sized grafts. Graft failure was significantly associated with ECD (p=0.039) and graft trephine size (p=0.04)., Conclusions: Larger grafts occupy a smaller chord length in the eye than the trephine size and are expected to provide 10%-20% more endothelial cells. Increased graft size and donor ECD is significantly associated with a reduced graft failure rate., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Aim: To determine the elimination kinetics of intracameral vancomycin administered as a bolus injection at the end of phacoemulsification cataract surgery., Methods: Vancomycin 1 mg/0.1 ml saline solution was administered to 19 patients by intracameral bolus injection at the end of routine cataract surgery. The aqueous concentration of vancomycin was determined in nine patients 1 minute after administration and in 10 patients 18-24 hours postoperatively. Aqueous samples were obtained by inserting a Rycroft cannula into the anterior chamber via the side port incision. Fluorescence polarisation immunoassay was used to calculate the aqueous vancomycin concentration., Results: The median (interquartile range) vancomycin concentration was 5458 (4756-6389) mg/l at 1 minute and 40.6 (25.9-47.1) mg/l 18 to 24 hours (median 19 hours) postoperatively. The vancomycin concentration exceeded the minimum inhibitory concentration (MIC) of endophthalmitis-causing gram-positive bacteria by a factor of 4 for up to 26 hours postoperatively. No adverse event or reaction was noted., Conclusion: Following bolus intracameral injection at the end of cataract surgery the concentration of vancomycin in the anterior chamber vastly exceeds its MIC for at least 24 hours but is predicted to fall below the MIC after 33 hours.

Aim: To determine the rate of development of ocular disease in patients presenting with mucous membrane pemphigoid (MMP) involving their oral mucosa., Methods: Diagnosis of oral MMP was made on the basis of clinical signs, histology, and direct and indirect immunofluorescence. Age, race, sex, age at diagnosis, progression of eye signs, duration of follow up, and time to progression of ocular disease were recorded., Results: 30 patients with established oral MMP were reviewed. The mean age at diagnosis was 65.2 years (range 46-84 years) and 16/30 (53%) were male. At initial ocular review nine (30%) patients showed ocular signs of pemphigoid, of whom two had mild (IIA IIIB), four moderate (IIB IIIC), and three severe (IIC IIID) disease. The mean interval between diagnosis of oral MMP and first ophthalmic review was 19.3 months (range 0-144). Over the period of follow up two (7%) patients developed ocular disease at 19 months and 48 months, respectively, despite having had no evidence of ocular involvement at presentation. In total, 11 (37%) patients with oral disease eventually showed ocular disease with a calculated incidence rate for the development of ocular disease of 0.03 per person year over 5 years., Conclusions: MMP may affect different tissues at different stages, often separated by many years. Patients with MMP involving their oral mucosa are at significant risk of developing ocular disease and should remain under ophthalmic review.

Background: The tear function index (TFI) has been shown to be of value in the diagnosis of patients suffering from Sjögren's syndrome. It is dependent, however, on introducing into the conjunctival fornix the correct concentration of fluorescein in at least one and a half times the normal tear volume. The stimulus and effect of this added volume on the tear dynamics is likely to vary between individuals. These factors, together with the method of performing the test, limit its general applicability., Aim: To devise a method of performing the TFI with less variability and more general applicability. To present a theoretical and in vitro assessment of the dynamics of the TFI., Method: The study was divided into three parts. The first part was to compare the results obtained using a prepared strip containing 1.3 microl of 0.5% fluorescein with the introduction of the same amount of fluorescein as a drop. The second part was to compare the results obtained with prepared strips with the standard method of performing the TFI, both with and without topical anaesthetic. The third part was an in vitro study of the rate of flow of graded volumes on a filter paper strip. 42 subjects with a diagnosis of Sjögren's syndrome according to the European criteria and 126 without Sjögren's syndrome were included., Results: There was no significant difference between the results obtained with a prepared strip and the introduction of 1.3 microl into the eye before performing the Schirmer's test and TFI (0.1

Aims: To determine the sensitivity and specificity of culture, immunohistochemistry (IHC), the polymerase chain reaction (PCR), and in situ hybridisation (ISH) for detecting herpes simplex virus (HSV-1) in the cornea of patients undergoing penetrating keratoplasty. To compare the incidence of HSV-1 in the cornea with that of varicella zoster virus (VZV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV)., Methods: The corneas of 110 patients, 52 with a documented history of herpes keratitis (HSK) and 58 with non-herpetic corneal disease, were investigated using IHC, PCR, ISH, and culture., Results: HSV-1 DNA and antigen were detected in 82% and 74% respectively, of corneas of patients with HSK and in 22% and 15% of corneas of patients with no history of HSK. The sensitivity of PCR and IHC was 82% and 74% with a specificity of 78% and 85%, respectively. HSV-1 DNA and antigen were found more frequently and in increased amounts in corneas of patients with a short interval between their last attack of HSK and surgery. There was a good correlation between PCR and IHC in 71%. HSV-1 was isolated by culture in 2%. Latency associated transcripts were not detected using ISH. Evidence of VZV DNA or antigen was found significantly more frequently in the corneas of patients with a history of HSK (p<0.001). No evidence of EBV or CMV was found in any cornea., Conclusions: PCR and IHC are both sensitive for the detection of HSV-1 in the cornea. A combination of PCR and IHC increases the specificity for the diagnosis of HSK to 97%. HSV-1 appears to be slowly removed from the cornea. VZV and HSV-1 may co-infect the cornea.

To determine whether the pattern electroretinogram can improve the objectivity of visual field assessment, 39 patients with glaucoma and ocular hypertension were studied. This was to establish whether there is a correlation between the pattern electroretinogram and the global indices (mean deviation and corrected pattern standard deviation) provided by automated perimetry using the Humphrey visual field analyser. A significant correlation was found between the amplitude of the P50 + N95 wave of the pattern electroretinogram and the mean deviation and corrected pattern standard deviation components of the visual field. The larger the deviation from normal of these indices, particularly the corrected pattern standard deviation, the smaller the amplitude of the pattern electroretinogram. This correlation between the pattern electroretinogram and visual field indices provides an additional measure of confidence when interpreting equivocal results of automated perimetry.

Surgical results can be assessed as a function of what was aimed for, what was done, and what was achieved. One of the aims of refractive surgery is to reduce astigmatism; the smaller the postoperative astigmatism the better the result. Determination of what was done--that is, the surgical effect, can be calculated from the preoperative and postoperative astigmatism. A simplified formulation is described which facilitates the calculation (magnitude and direction) of this surgical effect. In addition, an expression for surgical accuracy is described, as a function of what was aimed for and what was achieved.

Primary ocular herpes is usually seen as a follicular conjunctivitis and blepharitis, with or without involvement of the cornea. It is unknown, however, to what extent asymptomatic and/or subclinical primary disease occurs, and whether primary ocular herpes follows direct droplet spread to the eye. Previous models of murine ocular herpes have used trauma (scarification) to introduce virus into the cornea, producing disease which results in significant corneal scarring. To mimic a likely route of infection in humans, a droplet containing virus was placed on the mouse eye and clinical disease recorded. At least 1 month after inoculation, serum was assayed for neutralising antibodies and the cornea, iris, and trigeminal ganglion were investigated for evidence of herpes simplex virus type 1, by cocultivation and the polymerase chain reaction. Some animals showed a severe ulcerative blepharitis with little to no involvement of the cornea, while disease was undetectable in others. The development of disease depended on the dose and strain of virus and age of the animal, with older mice appearing more resistant. Virus was isolated from the trigeminal ganglion of younger animals inoculated with higher doses of virus, after 21 days in culture, suggesting that latency had been established. Neutralising antibodies were present in most mice irrespective of the presence of recognisable clinical disease. Using primers for the thymidine kinase and glycoprotein C regions of the viral genome, herpes simplex virus type 1 DNA was found in the cornea, iris, and trigeminal ganglion of most animals and showed a good correlation with the presence of neutralising antibodies. It would thus appear that herpes simplex virus type 1 is able to accede into the cornea, iris, and trigeminal ganglion following nontraumatic application of virus onto the mouse eye. This model mimics primary ocular disease in humans and may be useful for studies on recurrent disease and the spread of ocular herpes.

Patients undergoing penetrating keratoplasty for prior herpes simplex keratitis (group A) and corneal disease unrelated to herpes simplex (group B) were investigated to assess whether the cornea is a site for herpes simplex viral latency. All patients were seropositive for herpes simplex viral antibody. Virus was isolated from the tear film postoperatively in one patient and on cocultivation from the cornea of another patient. Herpes simplex viral DNA, however, was detected in the corneas of all patients from group A and half of those from group B by means of the polymerase chain reaction and primers to three well separated regions of the viral genome. Three donor corneas had no evidence of herpes simplex viral DNA. Using RNA polymerase chain reaction, we found evidence of a latency associated transcript and also that of a glycoprotein C coding transcript in two corneas, indicating viral replication. Nine corneas had evidence of a latency associated transcript but no glycoprotein C transcript, which suggests that herpes simplex virus may be maintained in a latent state in the corneas of patients with prior herpes simplex keratitis and in some patients with corneal disease unrelated to the herpes simplex virus.

The presence, frequency, and relationship of ocular and oral shedding of herpes simplex virus to previous herpes keratitis was investigated. This was to determine if a history of herpes keratitis predisposes to shedding of the herpes simplex virus into the tear film and/or mouth. Swabs were collected from the eyes and mouth of two groups of patients thrice weekly over a two- to four-month period. Group A comprised nine patients with a history of herpes labialis, group B 15 patients with a history of herpes keratitis. Herpes simplex virus type 1 was isolated from 1.33% of mouth specimens but was not identified in any of the ocular specimens. There was no significant difference between groups A and B in terms of ocular or oral shedding. Oral shedding appears to be independent of a previous herpes keratitis. The tear film is an unlikely source of virus in persons either with no history of herpes keratitis or between attacks in those patients with a history of previous herpes keratitis.

The statistical basis underlying the use of several visual acuity charts is examined. A new chart which offers theoretical and practical advantages for visual acuity screening is described.