Sodium Metabisulfite Inhibits Acanthamoeba Trophozoite Growth through Thiamine Depletion.

Acanthamoeba keratitis (AK) is a severe infection of the cornea. Prevention and treatment are difficult due to the inefficacy of currently available compounds. The impact of many commonly used compounds for routine examinations of Acanthamoeba is unexplored but might offer insight useful in combatting AK. In this study, we demonstrate that sodium metabisulfite, a common preservation constituent of eye care solutions, was found to be active against Acanthamoeba trophozoites at concentrations lower than that commonly found in eye drops (IC50 0.03 mg/mL). We demonstrate that sodium metabisulfite depletes thiamine from growth medium and that Acanthamoeba is a thiamine auxotroph, requiring thiamine salvage for growth. The inhibitory effects of sodium metabisulfite can be overcome by thiamine supplementation. These results are consistent with the lack of key enzymes for thiamine biosynthesis in the genome of Acanthamoeba, an area which might prove exploitable using new or existing compounds. Indeed, this study highlights sodium metabisulfite as a useful inhibitor of Acanthamoeba castellanii trophozoites in vitro and that it acts, at least in part, by limiting available thiamine.

Novel application of Deep Anterior Lamellar Keratoplasty for retinal detachment repair in totally opaque cornea secondary to aniridia.

PURPOSE: We present a novel approach for managing retinal detachment in a patient with aniridia related corneal scarring precluding fundal view via a deep anterior lamellar keratoplasty. METHODS: A 30-year-old female patient who had bilaterally opaque cornea, due to advanced aniridia related keratopathy presented with, experiencing flashing of light in her right eye. Examination of the retinal fundus was not possible due to the dense corneal scarring and underlying cataract. A superior bullous macula off retinal detachment was diagnosed on ultrasonography. Visual acuity at presentation was hand motions. The corneal scarring extended to the mid to deep stroma. We performed a deep anterior lamellar dissection of the opacified corneal stroma, that allowed clear visualisation of a dense cataract. The cataract was removed by phacoemulsification and IOL inserted. This allowed to proceed with repair of retinal detachment, through pars plana approach. The surgery was completed by a donor deep lamellar keratoplasty. RESULTS: This achieved a good fundal view to proceed with phacovitrectomy visualised through the residual corneal layers. Uneventful pars plana vitrectomy, cryotherapy and SF6 gas were performed to reattach the retina. Post-operatively the graft remains clear at 6 months with a visual acuity of 20/160 in the right eye, a level of vision the patient had not experienced for decades. CONCLUSION: Deep anterior lamellar keratoplasty offered an alternative to temporary keratoprosthesis to achieve a clear view of the retinal fundus and perform pars plana vitrectomy and repair of the retinal detachment.

Potential cost of assumptions within a visual assessment.

We report a man in his 80s who described sudden unilateral loss of vision, resulting in extensive urgent investigations by the accident and emergency department team. Subsequent evaluation of visual acuity with pinhole demonstrated significant improvement, triggering further questioning. It transpired that he was mistakenly wearing his wife's glasses, which accounted for his visual symptoms. This case illustrates the importance of a stepwise approach to visual assessment, and avoiding assumptions, as using the simple pinhole test could have avoided extensive investigations and their subsequent costs.

Novel Map Biopsy Technique to Define the Extent of Infection Before Penetrating Keratoplasty for Acanthamoeba Keratitis.

PURPOSE: The purpose of this study was to report a novel approach of prepenetrating keratoplasty (PKP) corneal map biopsies to define the extent of Acanthamoeba cyst infiltration in recalcitrant Acanthamoeba keratitis. METHODS: Corneal map biopsies were performed 1 week before PKP. Four biopsies, 1 from each peripheral corneal quadrant, were obtained to delineate the extent of microscopic infection. Histological results of these map biopsies were used to determine the size and location of the subsequent PKP. RESULTS: In our first case, map biopsies revealed Acanthamoeba cysts in 2 of the 4 biopsies. This led to an inferotemporally eccentric 8.5-mm PKP. The final histology report indicated that the closest resection margin was 0.08 mm. In our second case, the peripheral map biopsies were clear and an inferiorly eccentric 8.25-mm PKP was performed. The final histology report indicated that the closest resection margin was 2.3 mm. Both grafts have remained clear at 6 months postoperatively. CONCLUSIONS: Map biopsies of the cornea can achieve total removal of the corneal tissues infested with Acanthamoeba cysts and prevent reinfection of the donor graft.

Case for conservative management of adenoviral pseudomembranous conjunctivitis.

The clinical course of adenoviral pseudomembranous conjunctivitis is mostly self-limiting and requires only supportive management measures; however, a minority of patients may develop severe inflammation in response to the virus, which can present as subepithelial infiltrates and pseudomembranes. In its most severe form, symblepharon can result from the inflammatory response resulting in longer-term clinical sequelae. The optimal management of adenoviral pseudomembranous conjunctivitis is poorly defined and while debridement is commonly recommended, there is limited evidence base to support this practice. In this paper, we present two cases of PCR-proven adenoviral pseudomembranous conjunctivitis managed conservatively with topical lubricants and corticosteroids rather than debridement to good effect.

Estimations of Critical Clear Corneal Incisions Required for Lens Insertion in Cataract Surgery: A Mathematical Aspect.

In a routine cataract operation cornea tissue may be damaged when an intra-ocular lens (IOL) injector of diameter between 1.467 and 2.011 mm is inserted through an empirically designed 2.2 mm corneal incision. We aimed to model and estimate the minimal length of the incision required to avoid wound tear. It was assumed that the damage was caused by tissue fracture at the tips of the incision, and this fracture could be studied using damage and fracture mechanics. The criterion of the damage was caused by a tear governed by the critical energy release rate (ERR) G c , which is tissue dependent. Analytical and numerical studies were both conducted indicating the possibility of a safe and effective incision in cataract surgery. Six commonly used IOL injection systems were examined. Our results suggested that the recommended 2.2 mm incision cannot be treated as a universal threshold. Quicker IOL insertion may reduce wound damage. It was also recommended to advance IOL injector via its minor axis, and to cut the tear preferably along the circumferential direction due to tissue orthotropy. This study provides useful information and a deeper insight into the potential for mechanical damage to the corneal wound in cataract surgery.

Should We Perform Early Cataract Surgery? A Patient Reported Outcome Study.

PURPOSE: Current guidance states that access to cataract surgery should not be restricted by visual acuity (VA); nevertheless, 6/12 is used as a cut-off criterion in some health institutions. This study aims to determine the benefits of performing cataract surgery in patients with VA of 6/9 or better in both eyes; determine whether these benefits change over time; and compare the benefit observed between early first eye and second eye surgery. PATIENTS AND METHODS: Fifty adults with VA at least 6/9 in the worst eye and no ocular comorbidity were recruited. The Visual Function Index (VF-14) and Impact of Visual Impairment (IVI) questionnaires were conducted pre-operatively, 4 months post-operatively, and 12 months post-operatively. The t-test or a non-parametric equivalent was used to compare averages between groups. RESULTS: The mean change in VF-14 from baseline to 4 months was 16.43 (95% CI 12.49-20.50, p < 0.001) and the median change in IVI was 6.5 (IQR 9.75, p < 0.001). There was no significant difference between 4-month and 12-month follow-up (p > 0.05). There was no significant difference in the change in visual function between the first and second eye surgery (p > 0.05). CONCLUSION: This study provides evidence that visual function improves after cataract surgery in patients with pre-operative VA of 6/9 or better. The improvement observed was clinically significant and unchanged a year after surgery. Visual function improved after second eye as much as after first eye surgery. Assessing patient reported visual function may give a more realistic indication of the benefit of early cataract surgery than relying on VA alone.

Patients' attitudes towards the potential use of stability tape to minimize head movements during cataract surgery.

INTRODUCTION: Head stabilization may reduce intra-operative risk during cataract surgery, but could be misinterpreted as "restraint." We wanted to establish patients' attitudes towards the potential use of stability-tape. MATERIALS AND METHODS: One-hundred consecutive patients attending for local-anaesthetic cataract surgery were asked to complete a pre-operative questionnaire. This explored patient concerns and views regarding intra-operative head movement and the potential use of stability-tape. RESULTS: All 100-patients completed the questionnaire. The median head movement concern score was 2 out of 10 (range 1-9, IQR 1-5). Eighty-four percent felt stability tape should be offered to all patients and 97% would consent for its' use. Only 6% voiced concern about the use of stability-tape (95% CI 2.2%, 12.6%). CONCLUSION: Patients had low concern for moving their head during surgery. The concept of stability-tape to minimize head movements during cataract surgery was viewed positively by most patients. This strategy may promote safer surgery in selected cases.

Psychological complexities of visual restoration.

In this paper, we report the psychological and emotional experience of a patient who regained vision after over a decade of vision loss. The negative psychological implications of blindness are well recognised and there is a robust link between visual impairment and low mood and depressive symptoms. Although uncommon, low mood and depressive symptoms have been reported in patients whose sight has been restored, and lack of research gives rise to the possibility their prevalence may be grossly under-recognised in such patient groups. The effects can be so severe that patients may revert to living in darkness in mimicry of their previous lifestyle, effectively obviating the sight-restoring surgery. Healthcare professionals have a responsibility to address this traditionally neglected need by facilitating social, psychological and medical interventions that may ease the return to vision.

The Evolving Role of Ophthalmology Clinics in Screening for Early Alzheimer's Disease: A Review.

Alzheimer's disease (AD) is the leading cause of dementia, which is a growing public health concern. Although there is no curative treatment for established AD, early recognition and modification of the known risk factors can reduce both severity and the rate of progression. Currently, an early diagnosis of AD is rarely achieved, as there is no screening for AD. The cognitive decline in AD is gradual and often goes unnoticed by patients and caregivers, resulting in patients presenting at later stages of the disease. Primary care physicians (general practitioners in the UK) can administer a battery of tests for patients presenting with memory problems and cognitive impairment, however final diagnosis of AD is usually made by specialised tertiary level clinics. Recent studies suggest that in AD, visuospatial difficulties develop prior to the development of memory problems and screening for visuospatial difficulties may offer a tool to screen for early stage AD. AD and cataracts share common risk and predisposing factors, and the stage of cataract presentation for intervention has shifted dramatically with early cataract referral and surgical intervention becoming the norm. This presentation offers an ideal opportunity to administer a screening test for AD, and visuospatial tools can be administered at post-operative visits by eye clinics. Abnormal findings can be communicated to primary care physicians for further follow up and assessment, or possible interventions which modify risk factors such as diabetes, hypertension and obesity can be undertaken. We propose that eye clinics and ophthalmology facilities have a role to play in the early diagnosis of AD and reducing the burdens arising from severe dementia.

Virucidal benefits of povidone-iodine use on the ocular surface: a review.

Povidone-iodine (PVI) preparations are well known for their microbicidal effect. In ophthalmology, PVI is commonly used to sterilise the ocular surface prior to surgical procedures. It is also used uncommonly as treatment for adenoviral conjunctivitis, yet the virucidal benefits of PVI have not been clearly documented in existing clinical management guidelines for ocular surface conditions. The COVID-19 pandemic, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, has challenged traditional healthcare systems. The morbidity and mortality of this highly contagious disease have resulted in fatalities among healthcare workers, including ophthalmologists. The SARS-CoV-2 virus has been identified on conjunctival testing, a potential source of contagious infection which may be unrecognised in asymptomatic carriers. Concern has been raised that ocular procedures may be 'aerosol-generating' and the additional wearing of personal protective equipment has been recommended to protect operating theatre staff. This literature review demonstrates that PVI has a broad virucidal activity, including against coronaviruses. It is already used perioperatively as standard of ophthalmic care and has been shown clinically to be effective against adenoviruses on the ocular surface. The current surgical practice of application of 5%-10% PVI applied periocularly for 3 min seems to provide an adequate effective reduction in the patient's ocular surface viral load. The virucidal benefits of routine PVI use should be included in ophthalmology guidelines regarding safe ocular surgery protocols.

Modelling floppy iris syndrome and the impact of pupil size and ring devices on iris displacement.

INTRODUCTION: The aim of this paper was to further develop a previously described finite element model which equates clinical iris billowing movements with mechanical buckling behaviour, simulating floppy iris syndrome. We wished to evaluate the impact of pupil dilation and mechanical devices on normal iris and floppy iris models. METHODS: Theoretical mathematical modelling and computer simulations were used to assess billowing/buckling patterns of the iris under loading pressures for the undilated and dilated normal iris, the undilated and dilated floppy iris, and additionally with a mechanical ring device. RESULTS: For the normal iris, billowing/buckling occurred at a critical pressure of 19.92 mmHg for 5 mm pupil size, which increased to 28.00 mmHg (40.56%) with a 7 mm pupil. The Malyugin ring device significantly increased critical initiating buckling pressures in the normal iris scenario, to 34.58 mmHg (73.59%) for 7 mm ring with boundary conditions I (BC I) and 34.51 mmHg (73.24%) with BC II. For the most floppy iris modelling (40% degradation), initiating buckling value was 18.04 mmHg (-9.44%), which increased to 28.39 mmHg (42.52%) with the 7 mm ring. These results were much greater than for normal undilated iris without restrictive mechanical expansion (19.92 mmHg). CONCLUSION: This simulation demonstrates that pupil expansion devices inhibit iris billowing even in the setting of floppy iris syndrome. Our work also provides a model to further investigate the impact of pupil size or pharmacological interventions on anterior segment conditions affected by iris position.

Temporomandibular Disorder: An Important Cause of Temporal Headache in Patients Unlikely to Have Giant Cell Arteritis.

INTRODUCTION: Temporal headache often results in an Ophthalmology referral to rule out giant cell arteritis (GCA). When clinical suspicion of GCA is low, alternative diagnoses should be considered. Temporomandibular disorder (TMD) commonly causes a temporal headache. MATERIALS AND METHODS: Patients referred with a temporal headache attending the Friday emergency ophthalmology clinic from February to July 2017 were assessed for GCA using the American College of Rheumatology (ACR) diagnostic criteria and TMD using a validated screening questionnaire. RESULTS: Ten symptomatic patients presented and were screened for TMD during this period. Four had mild TMD, two moderate, and three severe. The mean TMD score in patients with less than 3 ACR GCA criteria was 14.75 (SD 4.03) versus 6.8 (SD 3.06) in patients with 3 or more criteria (p = 0.0075). CONCLUSION: TMD is an important cause of a temporal headache in patients unlikely to have GCA. Onward referral to dentistry for further management may be merited.

Allogeneic Ex Vivo Expanded Corneal Epithelial Stem Cell Transplantation: A Randomized Controlled Clinical Trial.

Limbal stem cell deficiency (LSCD) is a disease resulting from the loss or dysfunction of epithelial stem cells, which seriously impairs sight. Autologous limbal stem cell transplantation is effective in unilateral or partial bilateral disease but not applicable in total bilateral disease. An allogeneic source of transplantable cells for use in total bilateral disease can be obtained from culture of donated cadaveric corneal tissue. We performed a controlled multicenter study to examine the feasibility, safety, and efficacy of allogeneic corneal epithelial stem cells in the treatment of bilateral LSCD. Patients were randomized to receive corneal epithelial stem cells cultured on amniotic membrane (AM): investigational medicinal product (IMP) or control AM only. Patients received systemic immunosuppression. Primary endpoints were safety and visual acuity, secondary endpoint was change in composite ocular surface score (OSS). Sixteen patients were treated and 13 patients completed all assessments. Safety was demonstrated and 9/13 patients had improved visual acuity scores at the end of the trial, with no significant differences between IMP and control groups. Patients in the IMP arm demonstrated significant, sustained improvement in OSS, whereas those in the control arm did not. Serum cytokine levels were measured during and after the period of immune suppression and we identified strongly elevated levels of CXCL8 in the serum of patients with aniridia, which persisted throughout the trial. This first randomized control trial of allogeneic corneal epithelial stem cells in severe bilateral LSCD demonstrates the feasibility and safety of this approach. Stem Cells Translational Medicine 2019;8:323-331.

Assessing the accuracy of intracameral phenylephrine preparation in cataract surgery.

PURPOSE: Unpreserved phenylephrine is often used as an off-licence intracameral surgical adjunct during cataract surgery to assist with pupil dilation and/or stabilise the iris in floppy iris syndrome. It can be delivered as a neat 0.2 ml bolus of either 2.5 or 10% strength, or in a range of ad-hoc dilutions. We wished to assess the accuracy of intracameral phenylephrine preparation in clinical practice. METHODS: Phenylephrine 0.2 ml was analysed both neat (2.5 and 10%) and in diluted form (ratio of 1:1 and 1:3). Samples were analysed using the validated spectrophotometric method. RESULTS: A total of 36 samples were analysed. The standard curve showed linearity for phenylephrine (R2 = 0.99). Wide variability was observed across all dilution groups. There was evidence of significant differences in the percentage deviations from intended results between dilutions (p < 0.001). Mean percentage deviation for 1:3 dilution was significantly greater than neat (p = 0.003) and 1:1 dilution (p = 0.001). There was no evidence of a significant difference between 1:1 and neat (p = 0.827). CONCLUSIONS: Current ad-hoc dilution methods used to prepare intracameral phenylephrine are inaccurate and highly variable. Small volume 1 ml syringes should not be used for mixing or dilution of drug. Commercial intracameral phenylephrine products would address dosage concerns and could improve surgical outcomes in cases of poor pupil dilation and/or floppy iris syndrome.

Intraoperative head drift and eye movement: two under addressed challenges during cataract surgery.

PURPOSE: To objectively measure head drift during cataract surgery, and subjectively simulate eye movements and assess impact on surgical technique. MATERIALS AND METHODS: Twelve consecutively recorded routine cataract operations in the Tennent Institute of Ophthalmology, Gartnavel General Hospital, Glasgow, were reviewed. The speculum was used as a fixed point and correlated with a superimposed virtual ruler to measure maximum head drift in each direction throughout the operations. To simulate intraoperative eye movement, we attached string to the cataract surgical simulator (Eyesi) eye and manually induced abduction and adduction. A calibrated scale secured to the Eyesi head ensured 5 mm eye movements were consistently created. Ophthalmology trainees performed the continuous curvilinear capsulorhexis (CCC) exercise without and with sequential eye movements. Movements were induced every three seconds. Scores were compared using a paired Student's T-test. RESULTS: Mean head drift in the surgical recordings was 3.1 mm medially (range 2-7 mm), 2.9 mm laterally (range 2-4 mm), 2.6 mm superiorly (range 1-5 mm), and 1.9 mm inferiorly (range 1-4 mm). In 11 of 12 cases, the operating microscope had to be adjusted for head drift. Six junior trainees completed the CCC module on the Eyesi without then with eye movements. After introducing eye movements the mean Eyesi score reduced from 92.7 to 76.9 (P = 0.014), 'roundness of rhexis' score reduced from 89.4 to 57.5 (P = 0.020), and trainees operated 17 s faster (P = 0.016). CONCLUSION: This study objectively demonstrates the under-reported clinical scenario of head drift during cataract surgery. By manipulating the Eyesi we have shown that eye movements reduce the quality of cataract surgery.