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Alshaikh, Rasha A; Ryan, Katie B; Waeber, Christian
doi: 10.1136/bjophthalmol-2021-319115pmid: 33962970
Neovascular ocular diseases (such as age-related macular degeneration, diabetic retinopathy and retinal vein occlusion) are characterised by common pathological processes that contribute to disease progression. These include angiogenesis, oedema, inflammation, cell death and fibrosis. Currently available therapies target the effects of vascular endothelial growth factor (VEGF), the main mediator of pathological angiogenesis. Unfortunately, VEGF blockers are expensive biological therapeutics that necessitate frequent intravitreal administration and are associated with multiple adverse effects. Thus, alternative treatment options associated with fewer side effects are required for disease management. This review introduces sphingosine 1-phosphate (S1P) as a potential pharmacological target for the treatment of neovascular ocular pathologies. S1P is a sphingolipid mediator that controls cellular growth, differentiation, survival and death. S1P actions are mediated by five G protein-coupled receptors (S1P1–5 receptors) which are abundantly expressed in all retinal and subretinal structures. The action of S1P on S1P1 receptors can reduce angiogenesis, increase endothelium integrity, reduce photoreceptor apoptosis and protect the retina against neurodegeneration. Conversely, S1P2 receptor signalling can increase neovascularisation, disrupt endothelial junctions, stimulate VEGF release, and induce retinal cell apoptosis and degeneration of neural retina. The aim of this review is to thoroughly discuss the role of S1P and its different receptor subtypes in angiogenesis, inflammation, apoptosis and fibrosis in order to determine which of these S1P-mediated processes may be targeted therapeutically.
Mohney, Brian G; Sathiamoorthi, Saraniya; Frank, Ryan D
doi: 10.1136/bjophthalmol-2021-318853pmid: 33731363
Background/aimsTo determine if nasolacrimal massage or topical antibiotics are associated with higher rates of resolution compared with observation alone in a population-based cohort of infants with congenital nasolacrimal duct obstruction (CNLDO).MethodsThe medical records of all children <5 years diagnosed with CNLDO while residing in Olmsted County, Minnesota from 1 January 1995 through 31 December 2004 were retrospectively reviewed for type of management and non-surgical resolution of tearing.ResultsAmong 1958 infants diagnosed and followed for CNLDO, 516 (26.4%) were merely observed, 506 (25.8%) were prescribed massage alone, 485 (24.8%) were prescribed at least one course of topical antibiotics, 397 (20.3%) were prescribed both topical antibiotics and massage, and 54 (2.8%) had no documented therapy. Non-surgical resolution, occurring in 1669 (85.2%) during a median follow-up of 3.1 months (range: 1 week–248 months), was 74.6% for the merely observed, 89.7% for those prescribed digital massage, 87.0% for those prescribed antibiotics and 90.7% for those treated with both. This comparison was significant in unadjusted (p<0.001) and multivariable comparisons (p<0.001).ConclusionPrescribing topical antibiotics or digital massage for infants with CNLDO in this cohort, individually or in combination, was associated with a higher rate of spontaneous resolution than observation alone.
Patel, Sneh; Tohme, Natalia; Gorrin, Emmanuel; Kumar, Naresh; Goldhagen, Brian; Galor, Anat
doi: 10.1136/bjophthalmol-2020-318420pmid: 33789846
BackgroundChalazia are common inflammatory eyelid lesions, but their epidemiology remains understudied. This retrospective case–control study examined the prevalence, risk factors and geographic distribution of chalazia in a large veteran population.MethodsData on all individuals seen at a Veterans Affairs (VA) clinic between October 2010 and October 2015 were extracted from the VA health database. Subjects were grouped based on International Classification of Diseases, Ninth Revision (ICD-9) code for chalazion. Univariable logistic regression modelling was used to identify clinical and demographic factors associated with chalazion presence, followed by multivariable modelling to examine which factors predicted risk concomitantly. All cases were mapped across the continental US using geographic information systems modelling to examine how prevalence rates varied geographically.ResultsOverall, 208 720 of 3 453 944 (6.04%) subjects were diagnosed with chalazion during the study period. Prevalence was highest in coastal regions. The mean age of the population was 69.32±13.9 years and most patients were male (93.47%), white (77.13%) and non-Hispanic (93.72%). Factors associated with chalazion risk included smoking (OR=1.12, p<0.0005), conditions of the tear film (blepharitis (OR=4.84, p<0.0005), conjunctivitis (OR=2.78, p<0.0005), dry eye (OR=3.0, p<0.0005)), conditions affecting periocular skin (eyelid dermatitis (OR=2.95, p<0.0005), rosacea (OR=2.50, p<0.0005)), allergic conditions (history of allergies (OR=1.56, p<0.0005)) and systemic disorders (gastritis (OR=1.54, p<0.0005), irritable bowel syndrome (OR=1.45, p<0.0005), depression (OR=1.35, p<0.0005), anxiety (OR=1.31, p<0.0005)). These factors remained associated with chalazion risk when examined concomitantly.ConclusionPeriocular skin, eyelid margin and tear film abnormalities were most strongly associated with risk for chalazion. The impact of environmental conditions on risk for chalazion represents an area in need of further study.
Ferdi, Alex; Nguyen, Vuong; Kandel, Himal; Tan, Jeremy C K; Arnalich-Montiel, Francisco; Abbondanza, Marco; Watson, Stephanie
doi: 10.1136/bjophthalmol-2020-317547pmid: 33785509
AimsWe set out to identify risk factors for progression in untreated keratoconus patients from 34 centres across Australia, New Zealand, Spain and Italy.MethodsPatients were divided into ‘progressors’ and ‘stable’ patients for each clinical parameter: visual acuity (VA), steepest keratometry (maximum keratometry (Max-K)) and thinnest corneal thickness (TCT). Primary outcomes were the proportion of eyes with sustained progression in VA, Max-K or TCT within 3 years. Secondary outcomes included predictors of progression.ResultsThere were 3994 untreated eyes from 2283 patients. The proportion of eyes with VA, Max-K and TCT progression at 1 year were 3.2%, 6.6% and 3.1% respectively. Factors associated with VA loss were higher baseline VA (HR 1.15 per logMAR line increase in VA; p<0.001) and steeper baseline Max-K (HR 1.07 per 1D increase; p<0.001). Younger baseline age was associated with Max-K steepening (HR 0.96 per year older; p=0.001). Thicker baseline TCT, steeper baseline Max-K and younger baseline age were associated with TCT thinning: (HR 1.08 per 10 µm increase in TCT; p<0.001), (HR 1.03 per 1D increase; p=0.02) and (HR 0.98 per year younger; p=0.01), respectively.ConclusionsSteeper Max-K and younger age were the most clinically useful baseline predictors of progression as they were associated with worsening of two clinical parameters. Every 1D steeper Max-K was associated with a 7% and 3% greater risk of worsening VA and thinning TCT, respectively. Each 1 year younger was associated with a 4% and 2% greater risk of steepening Max-K and thinning TCT, respectively.
Ang, Marcus; Foo, Valencia; Ke, Mengyuan; Tan, Bingyao; Tong, Louis; Schmetterer, Leopold; Mehta, Jodbhir S
doi: 10.1136/bjophthalmol-2021-318847pmid: 33785510
PurposeTo study the role of two anterior segment optical coherence tomography angiography (AS-OCTA) systems in eyes with acute chemical injury.MethodsProspective study in subjects with unilateral chemical injuries. Sequential slit-lamp assessment with spectral domain (SD) (AngioVue, Optovue, USA) and swept source (SS) (Plex Elite, Zeiss, Carl Zeiss Meditec, Dublin, California, USA) AS-OCTA was performed in both eyes within 24–48 hours of injury. Subjects were managed with a standard clinical protocol and followed-up for 3 months. We assessed limbal disruption (loss of normal limbal vessel architecture), limbal vessel density measurements and agreement (kappa coefficient, κ) between masked assessors of limbal disruption based on AS-OCTA scans and slit-lamp assessment.ResultsTen subjects with median age 31 (25–33) years, 20% women, 60% suffered alkali injuries (Roper-Hall grade 1.5±0.7, Dua grade 2.3±1.2) at presentation. Mean limbal vessel density was lower in quadrants of affected eyes compared with controls detected by SD AS-OCTA (9.4%±2.0% vs 15.5%±1.8%, p<0.001) and SS AS-OCTA (8.8%±2.5% vs 13.9%±1.3%, p=0.01). There was substantial agreement when assessing limbal disruption on AS-OCTA (κ=0.7) compared with slit-lamp evaluation (κ=0.4). Overall, we found good agreement between SD and SS AS-OCTA systems in assessing limbal vessel density in eyes with chemical injury at presentation (mean paired difference: −1.08, 95% CI −3.2 to 0.5; p=0.189).ConclusionsIn this pilot study, AS-OCTA provided objective, non-contact, rapid assessment of limbal vasculature involvement in eyes with acute chemical injury. Further studies are required to establish the role of AS-OCTA in determining the prognosis of eyes with chemical injury.
Elsana, Baker; Gradstein, Libe; Imtirat, Ahed; Yagev, Ronit; Barrett, Chiya; Ling, Galina; Abu Tailakh, Muhammad; Baidousi, Amjad; Tsumi, Erez
doi: 10.1136/bjophthalmol-2020-317464pmid: 33753408
AimTo describe ocular manifestations in children with congenital insensitivity to pain with and without anhidrosis (CIPA and CIP).MethodsWe reviewed records of eye examinations of 39 children diagnosed with CIPA or CIP. We collected clinical data, with particular attention to ocular surface findings. Corneal sensitivity was tested by presence of a blink reflex upon touching the cornea. Statistical analysis assessed differences in manifestations between the two conditions, and relationships among corneal sensitivity, presence of corneal opacities and visual acuity (VA).ResultsCIPA was diagnosed in 32 children and CIP in 7. The median follow-up periods were 50 months (CIPA group) and 94 months (CIP group). Corneal opacities were present in 23% of CIPA eyes and in 57% of CIP eyes. A blink reflex was positive in 52% of CIPA eyes and in 33% of CIP eyes. We recorded VA ≥20/25 in 36% of CIPA eyes, whereas all patients with CIP had VA ≤20/30. For the whole cohort, we found a negative correlation between a preserved blink reflex and the presence of corneal opacities, and a positive correlation between a preserved blink reflex and VA ≥20/25.ConclusionChildren with congenital insensitivity to pain are prone to develop corneal scarring. Patients with CIP tend to have more severe ocular surface disease than those with CIPA, probably due to more prevalent loss of corneal sensation. In both groups, a preserved blink reflex correlated with good vision. Affected children should have close follow-up to promptly treat ocular surface disease and prevent vision loss.
Li, Tingyang; Stein, Joshua; Nallasamy, Nambi
doi: 10.1136/bjophthalmol-2020-318321pmid: 33836989
AimsTo assess whether incorporating a machine learning (ML) method for accurate prediction of postoperative anterior chamber depth (ACD) improves the refraction prediction performance of existing intraocular lens (IOL) calculation formulas.MethodsA dataset of 4806 patients with cataract was gathered at the Kellogg Eye Center, University of Michigan, and split into a training set (80% of patients, 5761 eyes) and a testing set (20% of patients, 961 eyes). A previously developed ML-based method was used to predict the postoperative ACD based on preoperative biometry. This ML-based postoperative ACD was integrated into new effective lens position (ELP) predictions using regression models to rescale the ML output for each of four existing formulas (Haigis, Hoffer Q, Holladay and SRK/T). The performance of the formulas with ML-modified ELP was compared using a testing dataset. Performance was measured by the mean absolute error (MAE) in refraction prediction.ResultsWhen the ELP was replaced with a linear combination of the original ELP and the ML-predicted ELP, the MAEs±SD (in Diopters) in the testing set were: 0.356±0.329 for Haigis, 0.352±0.319 for Hoffer Q, 0.371±0.336 for Holladay, and 0.361±0.331 for SRK/T which were significantly lower (p<0.05) than those of the original formulas: 0.373±0.328 for Haigis, 0.408±0.337 for Hoffer Q, 0.384±0.341 for Holladay and 0.394±0.351 for SRK/T.ConclusionUsing a more accurately predicted postoperative ACD significantly improves the prediction accuracy of four existing IOL power formulas.
Kamiya, Kazutaka; Hayashi, Ken; Tanabe, Mao; Tabuchi, Hitoshi; Sato, Masaki; Gotoh, Norihito; Kojima, Takashi; Hatsusaka, Natsuko
doi: 10.1136/bjophthalmol-2021-318825pmid: 34108223
AimTo compare the preoperative biometric data and the refractive accuracy of cataract surgery among major surgical sites in a nationwide multicentre study.MethodsWe prospectively obtained the preoperative biometric data of 2143 eyes of 2143 consecutive patients undergoing standard cataract surgery at major 12 facilities and compared the preoperative biometry as well as the postoperative refractive accuracy among them.ResultsWe found significant differences in most preoperative variables, such as axial length (one-way analysis of variance, p=0.003), anterior chamber depth (p<0.001), lens thickness (p<0.001) and central corneal thickness (p<0.001), except for mean keratometry (p=0.587) and corneal astigmatism (p=0.304), among the 12 surgical sites. The prediction error using the Sanders-Retzlaff-Kraff/Theoretical (SRK/T formula was significantly more hyperopic than that using the Barrett Universal II formula (paired t-test, p<0.001). The absolute error using the SRK/T formula was significantly larger than that using the Barrett Universal II formula (p=0.016). The prediction error using the SRK/T formula was significantly more hyperopic than that using the Barrett Universal II formula at 10 of 12 institutions, but significantly more myopic at one institution. The absolute error using the SRK/T formula was significantly larger than that using the Barrett Universal II formula at 4 of 12 institutions but significantly smaller at two institutions.ConclusionsRegional divergences of the preoperative biometry were not necessarily negligible, and the optimised intraocular lens power calculation formula was individually different among the 12 facilities. Our findings highlight the importance of individual optimisation of these formulas at each facility, especially in consideration of these biometric variations.Trial registration numberClinical Trial Registry; 000039976.
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