Myopia control and prevention: From lifestyle to low-concentration atropine. The 2022 Josh Wallman Memorial Lecture.

The purpose of this study was to explore the findings from the Hong Kong Children Eye Study and the Low Concentration Atropine for Myopia Progression (LAMP-1) Study. The incidence of myopia among schoolchildren in Hong Kong more than doubled during the COVID-19 pandemic, with outdoor time decreased significantly and screen time increased. The change in lifestyle during the COVID-19 pandemic aggravated myopia development. Low-concentration atropine (0.05%, 0.025% and 0.01%) is effective in reducing myopia progression with a concentration-related response. This concentration-dependent response was maintained throughout a 3-year follow-up period, and all low concentrations were well tolerated. An age-dependent effect was observed in each treatment group with 0.05%, 0.025% and 0.01% atropine. Younger age was associated with a poor treatment response to low-concentration atropine. Additionally, low-concentration atropine induced choroidal thickening along a concentration-dependent response throughout the treatment period. During the third year, continued atropine treatment achieved a better effect across all concentrations compared with the washout regimen. Stopping treatment at an older age and receiving lower concentration were associated with a smaller rebound effect. However, differences in the rebound effect were clinically small across all the three concentrations studied.

Betaine- and L-Carnitine-Based Ionic Liquids as Solubilising and Stabilising Agents for the Formulation of Antimicrobial Eye Drops Containing Diacerein.

The therapeutic efficacy of topically administered drugs, however powerful, is largely affected by their bioavailability and, thus, ultimately, on their aqueous solubility and stability. The aim of this study was to evaluate the use of ionic liquids (ILs) as functional excipients to solubilise, stabilise, and prolong the ocular residence time of diacerein (DIA) in eye drop formulations. DIA is a poorly soluble and unstable anthraquinone prodrug, rapidly hydrolysed to rhein (Rhe), for the treatment of osteoarthritis. DIA has recently been evaluated as an antimicrobial agent for bacterial keratitis. Two ILs based on natural zwitterionic compounds were investigated: L-carnitine C6 alkyl ester bromide (Carn6), and betaine C6 alkyl ester bromide (Bet6). The stabilising, solubilising, and mucoadhesive properties of ILs were investigated, as well as their cytotoxicity to the murine fibroblast BALB/3T3 clone A31 cell line. Two IL-DIA-based eye drop formulations were prepared, and their efficacy against both Staphylococcus aureus and Pseudomonas aeruginosa was determined. Finally, the eye drops were administered in vivo on New Zealand albino rabbits, testing their tolerability as well as their elimination and degradation kinetics. Both Bet6 and Carn6 have good potential as functional excipients, showing solubilising, stabilising, mucoadhesive, and antimicrobial properties; their in vitro cytotoxicity and in vivo ocular tolerability pave the way for their future use in ophthalmic applications.

2†Impact of COVID-19 on a national serum eyedrops programme in the UK.

NHSBT run a Serum Eyedrops programme for the UK, providing Autologous (AutoSE) and Allogenic (AlloSE) eyedrops for patients affected by severe dry eyes. The service is based within the Eye & Tissue Bank in Liverpool.In February 2020 (pre-pandemic within the UK) there were 1052 patients on the programme. 34% received AutoSE and 66% AlloSE. Due to a recent change in central funding, referrals for AlloSE had increased, creating a waiting list; in March 2020 the list had 72 patients.In March 2020 government guidelines were introduced to reduce the spread of COVID-19. These measures presented a number of challenges for NHSBT and our ability to maintain the supply of Serum Eyedrops: i) Many AutoSE patients could not attend donation appointments, as they were clinically vulnerable and needed to shield. This issue was addressed by temporarily providing them with AlloSE. This was done with agreement between patients and consultants. As a result, the proportion of patients receiving AlloSE increased to 82%.ii) There was a reduced supply of AlloSE donations due to a general reduced attendance at blood donation centres. To deal with this, additional donor centres were recruited to collect AlloSE. In addition, the postponing of much elective surgery during the pandemic meant the demand for blood for transfusion reduced, enabling us to build up stock in anticipation of blood stocks reducing as the pandemic developed.iii) Our service was also impacted by reduced staffing levels, due to staff needing to shield or self-isolate, and the need to implement workplace safety measures. To address these problems, a new laboratory was created, allowing staff to dispense eyedrops and adhere to social distancing. It was also possible to re-allocate staff from other areas within the Eye Bank due to a reduction in demand for other grafts during the pandemic.iv) There were initial concerns over the safety of blood and blood products as to whether the transmission of COVID-19 was possible through blood. Following a stringent risk assessment by NHSBT clinicians, and implementation of additional safeguards around blood donation, it was agreed that provision of AlloSE was safe and could continue.Despite all the challenges created by the pandemic, the measures we implemented enabled us to maintain our SE service for existing patients, provide treatment for new referrals and accommodate a significant increase (25% in the 12 months following the beginning of the pandemic) in the number of patients requiring treatment.

Phlyctenular Keratoconjunctivitis in a Patient With COVID-19 Infection.

ABSTRACT: The coronavirus disease 2019 global pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several ophthalmic manifestations have been reported to be associated with SARS-CoV-2 infection, including conjunctivitis, acute sixth nerve palsy, and multiple cranial neuropathies. We present a unique case of unilateral phlyctenular keratoconjunctivitis in a 5-year-old boy in the setting of SARS-CoV-2 infection.

In vitro activity of cysteamine against SARS-CoV-2 variants.

Global COVID-19 pandemic is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Continuous emergence of new variants and their rapid spread are jeopardizing vaccine countermeasures to a significant extent. While currently available vaccines are effective at preventing illness associated with SARS-CoV-2 infection, these have been shown to be less effective at preventing breakthrough infection and transmission from a vaccinated individual to others. Here we demonstrate broad antiviral activity of cysteamine HCl in vitro against major emergent infectious variants of SARS-CoV-2 in a highly permissible Vero cell line. Cysteamine HCl inhibited infection of wild type, alpha, beta, gamma, delta, lambda, and omicron variants effectively. Cysteamine is a very well-tolerated US FDA-approved drug used chronically as a topical ophthalmic solution to treat ocular cystinosis in patients who receive it hourly or QID lifelong at concentrations 6 times higher than that required to inhibit SARS CoV-2 in tissue culture. Application of cysteamine as a topical nasal treatment can potentially1) mitigate existing infection 2) prevent infection in exposed individuals, and 3) limit the contagion in vulnerable populations.

Case report of transient corneal edema after immunization with adenovirus-vectored COVID-19 vaccine.

RATIONALE: To report a case of bilateral transient corneal edema presumably associated with adenovirus-vectored coronavirus disease 2019 (COVID-19) vaccination that resolved with eye drops treatment. PATIENT CONCERNS: A 55-year-old Asian woman presented with sudden onset of bilateral visual disturbance developed 6 days after immunization with an adenovirus-vectored COVID-19 vaccine (AstraZeneca, London, United Kingdom). She underwent uneventful cataract surgery in right and left eyes 2 months ago and maintained good visual acuity bilaterally. Slit-lamp examination showed bilateral mild corneal edema that was confirmed with anterior segment optical coherent tomography. Anterior chamber and vitreous were clear bilaterally. Both fundi were normal. DIAGNOSES: The patient was diagnosed with corneal edema following adenovirus-vectored COVID-19 vaccination. INTERVENTIONS: She was prescribed with prednisolone acetate 1% eye drops bilaterally. OUTCOMES: Treatment with topical steroid for 2 weeks resulted in resolution of the corneal edema and improvement of the visual acuity bilaterally. LESSONS: This case suggests that transient corneal edema can develop following adenovirus-vectored COVID-19 vaccination. Prompt ophthalmologic evaluation and treatment may improve the corneal edema.

Multiple Factors Causing Myopia and the Possible Treatments: A Mini Review.

The myopia epidemic has become a global public health problem. Although myopia is progressing worldwide, the recent coronavirus infections 2019 (COVID-19) outbreak has spurred myopia progression. The current evidence-based treatments for humans are atropine eye drops, optical treatment with defocus, use of orthokeratology, extending proximity working distance, pausing from near work every half hour and increased time outside the home. Studies on myopia using animal models have been conducted for more than 40 years. In recent years, new mechanisms of myopia suppression have been revealed from animal experiments such as inflammation control, intraocular pressure control, light control, and the activity of early growth response protein 1 control. This mini-review provides a summary of the scientific evidence currently available on the control of myopia, and the possible treatments mitigating myopia.

Noninvasive Visualization of the Tear Film Microaerosol During Noncontact Tonometry Measurements.

PURPOSE: To investigate the aerosol generation by a noninvasive real-time observation device and assess the conditions relating to aerosolization during intraocular pressure (IOP) measurements using a commercial noncontact tonometer (NCT). STUDY DESIGN: Prospective experimental and healthy eye studies. METHODS: In an initial experimental study, we devised a model mannequin eye to investigate how air puff pressure and IOP of the eye affected aerosol generation. In the human study including 20 healthy volunteer control subjects, the number of tear aerosol particles generated at 20 and 40 mm Hg air puff pressures with and without eye drop was investigated. The recorded aerosol visualization video was analyzed and the number of aerosol particles generated in 5 seconds after IOP measurement was measured. RESULTS: The experimental and human studies confirmed the aerosol generation during NCT measurements. In the experimental study, when the air puff pressures were set at 20 and 40 mm Hg, a lower IOP (5 mm Hg) generated significantly more aerosols than a higher IOP (25 mm Hg) (20 mm Hg, P = .0159; 40 mm Hg, P = .0079). There was also a significant positive correlation between the air puff pressure and the number of aerosol particles in both high- and low-IOP eyes (P < .001). At an air puff pressure of 40 mm Hg, the amount of aerosol generated was significantly higher with eye drop than without eye drop (P = .047). CONCLUSIONS: NCT generates significant aerosolization from the tear film, the amount of which is determined by the IOP and the air puff pressure and the presence of eye drop use before the measurements.

Hydrodynamic Interaction Between Tear Film and Air Puff From Noncontact Tonometry.

PURPOSE: The purpose of this study was to investigate the mechanism of potential droplet formation in response to air puff deformation with two noncontact tonometers (NCTs). METHODS: Twenty healthy volunteers were examined using two NCTs, Ocular Response Analyzer and Corvis ST, and two contact tonometers, iCare and Tono-Pen. High-speed videos of the tear film response were captured with at spatial resolution of 20 microns/pixel at 2400 fps. Droplet size, droplet velocity, distance between air puff impact location, and the tear meniscus-lid margin were characterized. RESULTS: One subject was excluded due to technical issues. Droplets were detected only in tests with instilled eye drop. Videos showed the tear film rolls away from the apex while remaining adherent to the ocular surface due to the tendency of the fluid to remain attached to a solid surface explained by the Coanda effect. Twelve out of 38 videos with an eye drop administration showed droplet formation. Only one resulted in droplets with predominantly forward motion, which had the shortest distance between air puff impact location and lower meniscus. This distance on average was 5.9 ± 1.1 mm. The average droplet size was 500 ± 200 µm. CONCLUSIONS: Results indicate no droplet formation under typical clinical setting. Hence, standard clinical use of NCT tests is not expected to cause droplets. NCT testing with eye drop administration showed droplet formation at the inferior eyelid boundary, which acts as a barrier and interrupts tear flow. TRANSLATIONAL RELEVANCE: Study of tear film interaction with NCT air puff shows that these tonometers are not expected to cause droplet formation in standard use and that if external drops are required, both eyelids should be held if patients need assistance to maintain open eyes to avoid droplets with predominantly forward motion.

The Impact of the Coronavirus Disease 2019 Pandemic on Adherence to Ocular Hypotensive Medication in Patients with Primary Open-Angle Glaucoma.

PURPOSE: Emerging evidence suggests that the coronavirus disease 2019 (COVID-19) pandemic is disrupting health behaviors such as medication adherence. The objective of this study was to determine whether adherence to ocular hypotensive medication was affected by the pandemic and to identify factors associated with this change. DESIGN: In this cohort study, we used a controlled interrupted time series design in which the interruption was the declaration of the COVID-19 pandemic in the United States on March 13, 2020. The 300-day monitoring period, which evenly bracketed this declaration, started on October 16, 2019, and ended on August 10, 2020. PARTICIPANTS: Patients with primary open-angle glaucoma enrolled in an ongoing longitudinal National Institutes of Health-funded study initiated before the onset of the pandemic were selected if they were prescribed ocular hypotensive medication and had adherence data spanning the 300-day period. METHODS: We applied segmented regression analysis using a "slope change following a lag" impact model to obtain the adherence slopes in the periods before and after the segmentation. We compared the 2 slopes using the Davies test. MAIN OUTCOME MEASURES: The main outcome measure was daily adherence to ocular hypotensive medication, defined as the number of doses taken divided by the number of doses prescribed, expressed in percent. Adherence was measured objectively using Medication Event Monitoring System caps. We assessed the associations between change in adherence and demographic, clinical, and psychosocial factors. RESULTS: The sample included 79 patients (mean age, 71 years [standard deviation, 8 years]). Segmented regression identified a breakpoint at day 28 after the declaration of the pandemic. The slope in the period after the breakpoint (-0.04%/day) was significantly different from zero (P < 0.001) and from the slope in the period before the breakpoint (0.006%/day; P < 0.001). Mean adherence in the period before the segmentation breakpoint was significantly worse in Black patients (median, IQR: 80.6%, 36.2%) compared with White patients (median, IQR: 97.2%, 8.7%; chi-square, 15.4; P = 0.0004). A significant positive association was observed between the Connor-Davidson resilience score and the change in slope between the periods before and after the breakpoint (P = 0.002). CONCLUSIONS: Adherence to ocular hypotensive medication worsened during the COVID-19 pandemic and seems to be related to patient resilience. This collateral consequence of the pandemic may translate into vision loss that may manifest beyond its containment.

Acute Corneal Epithelial Rejection of LR-CLAL After SARS-CoV-2 Vaccination.

PURPOSE: The purpose of this study was to report a case of acute corneal epithelial rejection of living-related conjunctival limbal allograft (LR-CLAL) after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. OBSERVATIONS: A 27-year-old woman developed acute epithelial rejection of LR-CLAL 2 weeks after receiving the SARS-CoV-2 vaccine. She received the LR-CLAL transplant 4 years and 7 months previously and had a stable clinical course with no history of rejection. She had an ABO blood group and human leukocyte antigen compatible donor, no systemic comorbidities, and no rejection risk factors. CONCLUSIONS: The novel SARS-CoV-2 vaccine upregulates the immune system to produce an adaptive immune response. The SARS-CoV-2 vaccine may potentially be associated with increased risk of rejection in those with ocular surface transplants.

Influence of coronavirus disease 2019 on myopic progression in children treated with low-concentration atropine.

PURPOSE: The outbreak of coronavirus disease 2019 (COVID-19) has caused many children to stay indoors. Increased near work and insufficient outdoor activities are considered important risk factors for myopic progression. This study aimed to compare the changes in myopic progression before and after COVID-19 in children treated with low-concentration atropine. METHODS: The records of 103 eyes of 103 children who were treated with low-concentration atropine eye drops were retrospectively reviewed. We classified children according to the concentration of atropine eye drops and children's age. The beginning of the pre-COVID-19 period was set from January 2019 to May 2019, and the endpoint was set in March 2020. The beginning of the post-COVID-19 period was set in March 2020, and the endpoint was set from January 2021 to March 2021. We evaluated the questionnaires administered to children's parents. RESULTS: A significant myopic progression was observed in the post-COVID-19 period compared to the pre-COVID-19 period in the 0.05% and 0.025% atropine groups (P < 0.001 and P = 0.020, respectively). For children aged 5 to 7 and 8 to 10 years, the axial elongations were significantly faster in the post-COVID-19 period than in the pre-COVID-19 period (P = 0.022 and P = 0.005, respectively). However, the rates of axial elongation and myopic progression were not significantly different between pre- and post-COVID-19 in children aged 11 to 15 years (P = 0.065 and P = 0.792, respectively). The average time spent using computers and smartphones and reading time were significantly increased, and the times of physical and outdoor activity were significantly decreased in the post-COVID-19 period compared to the pre-COVID-19 period. CONCLUSIONS: The rates of myopic progression have increased substantially after the spread of COVID-19 with an increase in the home confinement of children. Therefore, it is necessary to control the environmental risk factors for myopia, even in children undergoing treatment for the inhibition of myopic progression.

Contamination of multiuse eyedrop bottles by exhaled air from patients wearing face masks during the COVID-19 pandemic: Schlieren imaging analysis.

PURPOSE: To determine whether mask-induced redirected exhaled air through the superior mask gap contacts multiuse eyedrop bottles during drop administration and the efficacy of interventions to reduce such exposure. SETTING: Academic ophthalmology center. DESIGN: Interventional analysis. METHODS: Schlieren airflow imaging was taken of an examinee wearing frequently used face masks and enacting common clinical scenarios-with and without manual occlusion of the superior mask gap and/or neck extension-and maximum visible vertical breath plume height was quantified. Bottle height during eyedrop administration was measured for 4 ophthalmologists during instillation to 8 eyes of 4 subjects. RESULTS: Breath plume height (mean ± SD 275.5 ± 16.3 mm) was significantly greater than mean bottle height (13.9 ± 4.7 mm; P < .01). Plume height was reduced with manual mask occlusion vs without (P < .01) and was also lower than mean bottle height with manual mask occlusion (P < .01) but not in the absence of occlusion (P < .01). Neck extension alone did not adequately redirect liberated breath to prevent contact with a bottle. CONCLUSIONS: Exhaled air liberated from commonly worn patient face masks was able to contact multiuse eyedrop bottles during eyedrop administration. These findings have important patient safety implications during the coronavirus disease 2019 pandemic and with other respiratory pathogens because these multiuse bottles could potentially serve as vectors of disease. Occlusion of the superior mask gap significantly reduces breath contamination and should be strongly considered by eyecare providers during drop administration in eye clinics.

Acute Uveitis following COVID-19 Vaccination.

PURPOSE: To describe a case of juvenile idiopathic arthritis (JIA)-associated anterior uveitis after receiving the Sinopharm COVID-19 vaccine. METHODS: A retrospective case report. RESULTS: An 18-year-old girl, with a history of antinuclear antibody positive oligoarticular JIA, presented with bilateral anterior uveitis 5 days after the second dose of the Sinopharm COVID-19 vaccine. Ocular examination revealed anterior uveitis with reduced visual acuity in both eyes. Anterior segment optical coherence tomography showed hyperreflective dots in the anterior chamber (AC) and fine endothelial granularities representing the circulating cells in the AC. Uveitis in both eyes resolved gradually after topical steroid treatment without recurrence. CONCLUSION: This report demonstrates a potential causal association of COVID-19 vaccine with anterior uveitis.

COVID-19 Ocular Prophylaxis: The Potential Role of Ozonated-Oils in Liposome Eyedrop Gel.

Purpose: To assess whether ozonated-oil in liposome eyedrop gel (OED) could be used to prevent the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection in an in vitro infection model. Methods: First, we tested the efficacy of OED on in vitro cell regeneration and dry eye resolution in human corneal epithelial cells (hCE-2). Second, we assessed the in vitro anti-SARS-CoV-2 infection efficacy of OED using Vero E6 cells. Tissues were examined to assess different parameters: morphology, histology, and mRNA expression at 24 hours after treatment. Results: OED could restore 50% of the scratch in the monolayer of hCE-2 cells in vitro compared with the 25% obtained with phosphate-buffered saline solution (PBS). At 24 hours after treatment with OED, the number of microvilli and the mucin network were restored, as observed using scanning electron microscopy. In Vero E6 cells infected with a primary SARS-CoV-2 strain and treated with OED two times/day, viral replication was found to be inhibited, with a 70-fold reduction observed at 72 hours after infection compared with that under the untreated and PBS-treated conditions. Conclusions: SARS-CoV-2 transmission through the ocular surface should not be ignored. Although the prevalence of coronavirus disease 2019 conjunctivitis infection is low, the need for a barrier to prevent possible viral infection is warranted. OED treatment may prevent the risk of SARS-CoV-2 infection after 72 hours of twice-daily applications. Translational Relevance: Dry eye condition might be a risk factor for SARS-CoV-2 infection and OED treatment may have a preventive role.

Decreased effectiveness of 0.01% atropine treatment for myopia control during prolonged COVID-19 lockdowns.

The COVID-19 pandemic of 2020 and its' accompanied lockdowns impacted the entire globe in ways the world is only beginning to comprehend. In Israel, children age 9-15 had not been in a frontal classroom and been socially restricted from March 2020 till March 2021. Fourteen of these children that had been under myopia control treatment which had been effective prior to the pandemic were included in this retrospective study to learn if their myopia continued to stay under control, or if the unique environmental modifications affected their progression. The results showed that average increase in spherical equivalent refraction and axial length, measured with optical biometer OA-2000 (Tomey GmbH, Nagoya, Japan), during the year of lockdowns was -0.73 ± 0.46D/0.46 ± 0.31 mm respectively, while the average increase in the year prior was -0.33 ± 0.27D/0.24 ± 0.21 mm. Though several articles have indicated the pandemic environment has influenced myopia progression in children, this communication indicates a possible significant impact of the environment on myopia increase even in individuals under effective atropine treatment. These children's' progression suggests practitioners consider and address multiple aspects simultaneously when attempting myopia control.

Characteristics of endothelial corneal transplant rejection following immunisation with SARS-CoV-2 messenger RNA vaccine.

AIM: We report two cases of endothelial corneal allograft rejection following immunisation with SARS-CoV-2 messenger RNA (mRNA) vaccine BNT162b2 and describe the implications for management of transplant recipients postvaccination for COVID-19. METHODS: A 66-year-old woman with Fuchs endothelial corneal dystrophy (FECD) and a unilateral Descemet's membrane endothelial keratoplasty (DMEK) transplant received COVID-19 mRNA vaccine BNT162b2 14 days post-transplant. Seven days later, she presented with symptoms and signs of endothelial graft rejection. An 83-year-old woman with bilateral DMEK transplants for FECD 3 and 6 years earlier developed simultaneous acute endothelial rejection in both eyes, 3 weeks post second dose of COVID-19 mRNA vaccine BNT162b2. Rejection in both cases was treated successfully with topical corticosteroids. CONCLUSIONS: We believe this is the first report of temporal association between corneal transplant rejection following immunisation against COVID-19 and the first report of DMEK rejection following any immunisation. We hypothesise that the allogeneic response may have been initiated by the host antibody response following vaccination. Clinicians and patients should be aware of the potential of corneal graft rejection associated with vaccine administration and may wish to consider vaccination in advance of planned non-urgent keratoplasties. Patients should be counselled on the symptoms and signs that require urgent review to allow early treatment of any confirmed rejection episode.

Maternal finger-prick allogenic blood for persistent corneal epithelial defects.

This is a case of a 17-year-old patient with aniridia-related keratopathy and persistent epithelial defect (PED) treated successfully using maternal finger-prick blood (FPB). Maternal allogenic FPB treatment was initiated to the patient who was non-compliant with the use of autologous FPB. The PED was successfully managed with maternal FPB treatment with rapid and complete closure of the epithelial defect. Additionally, there was immediate and sustained symptomatic improvement to pain and recovery of vision in the only seeing eye. There was no immunological reaction to allogenic blood. Maternal finger-prick allogenic blood could serve as a potential alternative to serum eye drops or autologous FPB in the management of refractory PED, particularly in reference to the paediatric or the vulnerable age group. Further studies are required to confirm the role of allogenic blood in the treatment of PED.

Topical Ocular Povidone-Iodine as an Adjunctive Preventative Practice in the Era of COVID-19.

ABSTRACT: Ophthalmologists and patients have an inherent increased risk for transmission of SARS-CoV-2. The human ocular surface expresses receptors and enzymes facilitating transmission of SARS-CoV-2. Personal protective equipment alone provides incomplete protection. Adjunctive topical ocular, nasal, and oral antisepsis with povidone iodine bolsters personal protective equipment in prevention of provider-patient transmission of SARS-CoV-2 in ophthalmology.