Showing papers in "Eye in 2018"

Automated diabetic retinopathy detection in smartphone-based fundus photography using artificial intelligence.

Abstract: To assess the role of artificial intelligence (AI)-based automated software for detection of diabetic retinopathy (DR) and sight-threatening DR (STDR) by fundus photography taken using a smartphone-based device and validate it against ophthalmologist’s grading. Three hundred and one patients with type 2 diabetes underwent retinal photography with Remidio ‘Fundus on phone’ (FOP), a smartphone-based device, at a tertiary care diabetes centre in India. Grading of DR was performed by the ophthalmologists using International Clinical DR (ICDR) classification scale. STDR was defined by the presence of severe non-proliferative DR, proliferative DR or diabetic macular oedema (DME). The retinal photographs were graded using a validated AI DR screening software (EyeArtTM) designed to identify DR, referable DR (moderate non-proliferative DR or worse and/or DME) or STDR. The sensitivity and specificity of automated grading were assessed and validated against the ophthalmologists’ grading. Retinal images of 296 patients were graded. DR was detected by the ophthalmologists in 191 (64.5%) and by the AI software in 203 (68.6%) patients while STDR was detected in 112 (37.8%) and 146 (49.3%) patients, respectively. The AI software showed 95.8% (95% CI 92.9–98.7) sensitivity and 80.2% (95% CI 72.6–87.8) specificity for detecting any DR and 99.1% (95% CI 95.1–99.9) sensitivity and 80.4% (95% CI 73.9–85.9) specificity in detecting STDR with a kappa agreement of k = 0.78 (p < 0.001) and k = 0.75 (p < 0.001), respectively. Automated AI analysis of FOP smartphone retinal imaging has very high sensitivity for detecting DR and STDR and thus can be an initial tool for mass retinal screening in people with diabetes.

An overview of the clinical applications of optical coherence tomography angiography.

Abstract: Optical coherence tomography angiography (OCTA) has emerged as a novel, non-invasive imaging modality that allows the detailed study of flow within the vascular structures of the eye. Compared to conventional dye angiography, OCTA can produce more detailed, higher resolution images of the vasculature without the added risk of dye injection. In our review, we discuss the advantages and disadvantages of this new technology in comparison to conventional dye angiography. We provide an overview of the current OCTA technology available, compare the various commercial OCTA machines technical specifications and discuss some future software improvements. An approach to the interpretation of OCTA images by correlating images to other multimodal imaging with attention to identifying potential artefacts will be outlined and may be useful to ophthalmologists, particularly those who are currently still unfamiliar with this new technology. This review is based on a search of peer-reviewed published papers relevant to OCTA according to our current knowledge, up to January 2017, available on the PubMed database. Currently, many of the published studies have focused on OCTA imaging of the retina, in particular, the use of OCTA in the diagnosis and management of common retinal diseases such as age-related macular degeneration and retinal vascular diseases. In addition, we describe clinical applications for OCTA imaging in inflammatory diseases, optic nerve diseases and anterior segment diseases. This review is based on both the current literature and the clinical experience of our individual authors, with an emphasis on the clinical applications of this imaging technology.

Normal tension glaucoma: review of current understanding and mechanisms of the pathogenesis.

Abstract: Normal tension glaucoma (NTG) is an exception in the “glaucoma family” where the major risk factor, increased intraocular pressure, is missing. If not increased intraocular pressure, then what other causes can then lead to glaucomatous optic disc change and visual field loss in NTG? Several possibilities will be discussed. Among them a higher sensitivity to normal pressure, vascular dysregulation, an abnormally high translaminar pressure gradient and a neurodegenerative process due to impaired cerebrospinal fluid dynamics in the optic nerve sheath compartment. There are many excellent review papers published on normal tension glaucoma (NTG). The aim of this paper is therefore not to add another extensive review on NTG but rather to focus on and to discuss some possible mechanisms that are thought to be involved in the pathophysiology of NTG and to discuss the stronger and weaker aspects of each concept. The fact that several concepts exist suggests that NTG is still not very well understood and that no single mechanism on its own might adequately explain NTG.

Carotid-cavernous fistula: current concepts in aetiology, investigation, and management

Abstract: A carotid-cavernous fistula (CCF) is an abnormal communication between arteries and veins within the cavernous sinus and may be classified as either direct or dural. Direct CCFs are characterized by a direct connection between the internal carotid artery (ICA) and the cavernous sinus, whereas dural CCFs result from an indirect connection involving cavernous arterial branches and the cavernous sinus. Direct CCFs frequently are traumatic in origin and also may be caused by rupture of an ICA aneurysm within the cavernous sinus, Ehlers–Danlos syndrome type IV, or iatrogenic intervention. Causes of dural CCFs include hypertension, fibromuscular dysplasia, Ehlers–Danlos type IV, and dissection of the ICA. Evaluation of a suspected CCF often involves non-invasive imaging techniques, including standard tonometry, pneumotonometry, ultrasound, computed tomographic scanning and angiography, and/or magnetic resonance imaging and angiography, but the gold standard for classification and diagnosis remains digital subtraction angiography. When a direct CCF is confirmed, first-line treatment is endovascular intervention, which may be accomplished using detachable balloons, coils, liquid embolic agents, or a combination of these tools. As dural CCFs often resolve spontaneously, low-risk cases may be managed conservatively. When invasive treatment is warranted, endovascular intervention or stereotactic radiosurgery may be performed. Modern endovascular techniques offer the ability to successfully treat CCFs with a low morbidity and virtually no mortality.

Clinical pharmacology of intravitreal anti-VEGF drugs.

Abstract: Clinical efficacy of intravitreal anti-VEGF drugs has been widely demonstrated in several angiogenesis-driven eye diseases including diabetic macular edema and the neovascular form of age-related macular degeneration. Pegaptanib, ranibizumab, and aflibercept have been approved for use in the eye, whereas bevacizumab is widely used by ophthalmologists to treat patients “off-label”. These drugs are active in the nanomolar to picomolar range; however, caution is required when establishing the rank order of affinity and potency due to in vitro inter-experimental variation. Despite the small doses used for eye diseases and the intravitreal route of administration may limit systemic side effects, these drugs can penetrate into blood circulation and alter systemic VEGF with unknown clinical consequences, particularly in vulnerable groups of patients. Clinical pharmacokinetics of ocular anti-VEGF agents should therefore be taken into account when choosing the right drug for the individual patient. The gaps in current understanding that leave open important questions are as follows: (i) uncertainty about which drug should be given first, (ii) how long these drugs can be used safely, and (iii) the choice of the best pharmacological strategy after first-line treatment failure. The current review article, based on the information published in peer-reviewed published papers relevant to anti-VEGF treatments and available on the PubMed database, describes in detail the clinical pharmacology of this class of drugs to provide a sound pharmacological basis for their proper use in ophthalmology clinical practice.

Space flight-associated neuro-ocular syndrome (SANS)

Abstract: Interesting novel and somewhat perplexing physiologic and pathologic neuro-ocular findings have been documented in astronauts during and after long duration space flight (LDSF). These findings collectively have been termed the "space flight-associated neuro-ocular syndrome" (SANS). The National Aeronautics and Space Administration (NASA) in the United States has meticulously and prospectively documented the clinical, ultrasound, optical coherence tomography imaging, and radiographic findings of SANS including unilateral and bilateral optic disc edema, globe flattening, choroidal and retinal folds, hyperopic refractive error shifts, and nerve fiber layer infarcts (i.e., cotton wool spots). NASA and collaborating researchers continue to study SANS in preparation for future manned missions to space, including continued trips to the ISS, a return to the moon, or perhaps new voyages to the asteroid belt, or the planet, Mars.

Inflammasomes, the eye and anti-inflammasome therapy.

Abstract: Inflammasomes, key molecular regulators that play an important role in inflammation, consist of a central protein, an adaptor protein ASC (apoptosis speck-like protein) and a caspase-1 protein. Upon activation, caspase-1 induces maturation of cytokines such as interleukin-1β (IL-1β) and interleukin-18 (IL-18). The release of these cytokines can result in inflammation. Inflammasomes are activated by a variety of factors and their activation involves complex signalling leading to resolution of infection, but can also contribute to the pathology of inflammatory, autoimmune, and infectious diseases. The role of NLRP1, NLRP3, NLRC4 and AIM2 inflammasomes in the pathogenesis of ocular diseases such as glaucoma, age related macular degeneration (AMD), diabetic retinopathy, dry eye and infections of the eye has been established over the past decade. In experimental studies and models, inhibition of inflammasomes generally helps to reduce the inflammation associated with these eye diseases, but as yet the role of these inflammasomes in many human eye diseases is unknown. Therefore, a need exists to study and understand various aspects of inflammasomes and their contribution to the pathology of human eye diseases. The goal of this review is to discuss the role of inflammasomes in the pathology of eye diseases, scope for anti-inflammasome therapy, and current research gaps in inflammasome-related eye disease.

Optical coherence tomography in multiple sclerosis.

Abstract: To summarize recent findings regarding the utility of optical coherence tomography in multiple sclerosis. We searched PubMed for relevant articles using the keywords 'optical coherence tomography multiple sclerosis'. Additional articles were found via references in these articles. We selected articles based on relevance. Optical coherence tomography has contributed to greater insights into the pathophysiology of multiple sclerosis. Loss of retinal nerve fibre layer and ganglion cell layer thickness correlate with clinical and paraclinical parameters such as visual function, disability and magnetic resonance imaging. Some studies indicate that OCT parameters may be able to predict disability progression and visual function in MS. OCT angiography has recently emerged as a novel technique to study MS. OCT has proven very useful with regards to research, monitoring and predicting disability in multiple sclerosis. It will be interesting to see how OCT angiography will contribute to this field.

One-year result of XEN45 implant for glaucoma: efficacy, safety, and postoperative management

Abstract: To report the efficacy, safety profile, and postoperative management of XEN45 implant at 12-month follow-up. This was a retrospective, non-randomised interventional case series involving patients who underwent XEN45 implantation by a single, experienced glaucoma specialist in a tertiary centre. Primary outcome measures were the intraocular pressure (IOP) and the number of medications at 1-year follow-up visit. Two IOP criteria were chosen to measure success: IOP ≤21 mm Hg and ≥20% reduction from baseline (criteria one); and IOP ≤15 mm Hg and ≥30% reduction from baseline (criteria two). All 39 eyes completed 1-year follow-up. The mean preoperative IOP was 24.9±7.8 mm Hg on three drops, which reduced to 14.5±3.4 mm Hg at month 12 (P<0.005) on 0.7 drops (P<0.005). On the basis of criteria one, the cumulative probability of success at 1 year was 87.0% without medication and 92.0% with medication. On the basis of criteria two, cumulative probability of success was 62.0% without medication and 64.0% with medication. Bleb intervention with a median of 2 (range 1–4) was required for 51.3% of eyes. Implant was obstructed by iris tissue in three eyes (7.7%); one eye (2.6%) developed hyphaema; eight eyes (20.5%) had numerical hypotony (IOP≤5 mm Hg) at day 1, of which all spontaneously resolved by week 4 apart from one eye. The XEN45 implant proved to be an effective treatment with a good safety profile at 1-year follow-up period. The high rate of postoperative bleb intervention does not make XEN45 a ‘fit-and-forget’ procedure and therefore the procedure should ideally be performed by surgeons experienced in bleb management.

Cellular regeneration strategies for macular degeneration: past, present and future

Abstract: Despite considerable effort and significant therapeutic advances, age-related macular degeneration (AMD) remains the commonest cause of blindness in the developed world. Progressive late-stage AMD with outer retinal degeneration currently has no proven treatment. There has been significant interest in the possibility that cellular treatments may slow or reverse visual loss in AMD. A number of modes of action have been suggested, including cell replacement and rescue, as well as immune modulation to delay the neurodegenerative process. Their appeal in this enigmatic disease relate to their generic, non-pathway-specific effects. The outer retina in particular has been at the forefront of developments in cellular regenerative therapies being surgically accessible, easily observable, as well as having a relatively simple architecture. Both the retinal pigment epithelium (RPE) and photoreceptors have been considered for replacement therapies as both sheets and cell suspensions. Studies using autologous RPE, and to a lesser extent, foetal retina, have shown proof of principle. A wide variety of cell sources have been proposed with pluripotent stem cell-derived cells currently holding the centre stage. Recent early-phase trials using these cells for RPE replacement have met safety endpoints and hinted at possible efficacy. Animal studies have confirmed the promise that photoreceptor replacement, even in a completely degenerated outer retina may restore some vision. Many challenges, however, remain, not least of which include avoiding immune rejection, ensuring long-term cellular survival and maximising effect. This review provides an overview of progress made, ongoing studies and challenges ahead.

Selective laser trabeculoplasty: past, present, and future.

Abstract: Over the past two decades, selective laser trabeculoplasty (SLT) has increasingly become an established laser treatment used to lower intraocular pressure in open-angle glaucoma and ocular hypertensive patients. In this review we trace the origins of SLT from previous argon laser trabeculoplasty and review the current role it has in clinical practice. We outline future directions of SLT research and introduce emerging technologies that are further developing this intervention in the treatment paradigm of glaucoma.

Physical activity, visual impairment, and eye disease

Abstract: Numerous studies have demonstrated physical activity is a strong factor in overall health and well-being, and a growing body of literature, reviewed herein, suggests that several eye conditions, including glaucoma, age-related macular degeneration, and diabetic retinopathy, are associated with lower activity levels. Likewise, physical activity levels are lower in persons with worse vision. Research in this area has utilized both self-reported physical activity measures as well as objective measures of activity (i.e., accelerometers), each of which have their own strengths and limitations. Putative mechanisms explaining the association of various eye conditions with physical activity are discussed. It is possible that activity restriction occurs as a downstream consequence of eye disease/visual impairment, that activity restriction causes eye disease/visual impairment, or that causality is bidirectional; evidence supporting each of these theories is put forth. An improved understanding of the relationship between physical activity and eye disease will highlight potential secondary health risks resulting from eye disease, and can help determine whether activity might serve as a readily available preventative measure to prevent specific eye conditions.

Cataract in patients with diabetes mellitus—incidence rates in the UK and risk factors

Abstract: To analyze the risk of incident cataract (diagnosis or extraction) in patients with or without diabetes focusing on other comorbid conditions, antidiabetic drug use, and diabetes duration. The study population comprised newly diagnosed diabetes patients (≥40 years) from the UK-based Clinical Practice Research Datalink (CPRD) between 2000 and 2015, and a random sample of the general population matched for age, sex, general practice, and year of diabetes diagnosis. We assessed cataract incidence rates (IRs) and performed a nested case-control analysis in the diabetic cohort to assess potential risk factors for a cataract. There were 56,510 diabetes patients included in the study. IRs of cataract were 20.4 (95% CI 19.8–20.9) per 1000 person-years (py) in patients with diabetes and 10.8 (95% CI 10.5–11.2) per 1000 py in the general population. IRs increased considerably around the age of 80 years and with a concomitant diagnosis of macular edema. The incidence rate ratio (IRR) was highest in patients of the age group of 45–54 years. In the nested case-control study, we identified 5800 patients with cataract. Risk of cataract increased with increasing diabetes duration (adj. OR 5.14, 95% CI 4.19–6.30 diabetes for ≥10 years vs. diabetes <2 years). According to our study, diabetes is associated with an approximately two-fold increased detection rate of cataract. The risk of cataract associated with diabetes is highest at younger ages. Patients with diabetic macular edema are at an increased risk for cataract as well as patients with long-standing diabetes.

Neuroprotective agents in the management of glaucoma.

Abstract: Glaucoma is an optic neuropathy, specifically a neurodegenerative disease characterized by loss of retinal ganglion cells (RGCs) and their axons. The pathogenesis of RGC loss in glaucoma remains incompletely understood and a broad range of possible mechanisms have been implicated. Clinical evidence indicates that lowering intraocular pressure (IOP) does not prevent progression in all patients; therefore, risk factors other than those related to IOP are involved in the disease. The need for alternative, non-IOP-lowering treatments focused at preventing progression, that is, neuroprotectants, has become of interest to both the patient and the physician. Experimental evidence accumulated during the past two decades lend a great deal of support to molecules endowed with neuroprotective features. However, translation to the clinic of the latter drugs results unsuccessful mostly because of the lack of reliable in vivo measure of retinal damage, thus hampering the good therapeutic potential of neuroprotective agents given alone or as adjuvant therapy to IOP-lowering agents. Further research effort is needed to better understand the mechanisms involved in glaucoma and the means to translate into clinic neuroprotective drugs.

What do we know about the macular pigment in AMD: the past, the present, and the future.

Abstract: Carotenoids are lipophilic isoprenoid pigments with a common C40H56 core chemical structure that are naturally synthesized by many plants, algae, bacteria, and fungi. Humans and animals cannot synthesize carotenoids de novo and must obtain them solely through dietary sources. Among the more than 750 carotenoids in nature, only lutein, zeaxanthin, meso-zeaxanthin, and their oxidative metabolites selectively accumulate in the foveal region of the retina where they are collectively referred to as the macular pigment (MP) of the macula lutea. MP serves an ocular protective role through its ability to filter phototoxic blue light radiation and also via its antioxidant activity. These properties have led to the hypothesis that carotenoids may protect against the development of age-related macular degeneration (AMD), the most common cause of blindness in the aged population >60 years old. Epidemiological studies have supported this by showing that patients with lower concentrations of serum carotenoids and macular pigment optical density (MPOD) measurements are at a higher risk of developing AMD. Conversely, nutritional supplementation and diets rich in lutein and zeaxanthin readily impact MP concentrations and reduce the risk of progression to advanced AMD, and the AREDS2 supplement formulation containing 10 mg of lutein and 2 mg of zeaxanthin is the standard-of-care recommendation for individuals at risk for visual loss from advanced AMD. This article reviews the rich history of research on the MP dating back to the 1700s and outlines their potential for further therapeutic improvements for AMD in the future.

Evaluation of 3D heads-up vitrectomy: outcomes of psychometric skills testing and surgeon satisfaction.

Abstract: To evaluate the use of a three-dimensional heads-up microscope (3DM) during 25-gauge pars plana vitrectomy (PPV) compared with a traditional ophthalmic microscope (TM) in terms of efficacy, safety, and teaching and learning satisfaction. Prospective comparative interventional study. Fifty eyes affected by one of the following diseases: rhegmatogenous or tractional retinal detachment, epiretinal membrane, full-thickness macular hole, vitreous hemorrhage, or dropped lens. The 50 eyes were randomly assigned to one of two groups: group A (25 eyes) underwent 25-gauge PPV with 3DM, and group B (25 eyes) underwent 25-gauge PPV with TM. The main outcome measures were the duration of the operation, intraoperative complications, and surgeon and observer satisfaction. A questionnaire was used to assess surgeon satisfaction according to the following parameters: comfort, visibility, image quality, depth perception, simplicity of use, maneuverability, and teaching. A questionnaire to assess observer satisfaction was completed by 20 observers (surgical residents or ophthalmic surgeons). The degree of satisfaction was higher using 3DM for both surgeons and observers (P < 0.001). The average duration of the operation did not differ significantly between the two methods. No major complications occurred for either method. PPV with 3DM is more comfortable for the surgeon and poses no substantially greater risk of complications for the patient. The high-definition screen delivers excellent depth perception and better screen parameter control, which results in high-quality surgical performance. 3DM surgery helps to significantly improve teaching and learning intra-operative surgical procedures.

A 10-year analysis of microbiological profiles of microbial keratitis: the North East England Study.

Abstract: Tan et al. [1] recently reported a 12-year analysis of microbial keratitis in a tertiary eye centre (Manchester) in which they found a significant decreasing trend in Grampositive keratitis along with an increasing trend in Moraxella keratitis. According to the literature and our experience, Moraxella keratitis is known for its chronicity and slow response to treatment [2, 3]. In view of their findings, we performed a 10-year retrospective analysis (January 2008–December 2017) on the microbiological profiles of microbial keratitis in Sunderland Eye Infirmary (one of the three main eye centres in the North East of England) to determine if the changing trend of microbial keratitis was similar across the UK. During our study period, a total of 407 positive corneal scrapes (out of 914 scrapes) were identified, giving a yield rate of 44.5%. Of 407 cases, 212 (52.1%) were female and mean age was 55.9 (SD 21.0) years; 57 (14.0%) cases were polymicrobial. A total of 478 organisms were isolated; these included 308 (64.9%) Gram-positive and 127 (26.2%) Gram-negative organisms, 20 (4.2%) fungal, and 23 (4.8%) acanthamoeba. For descriptive and analytic purposes, the study was divided into two time periods, namely 2008–2012 and 2013–2017. We observed a similar increasing trend in Moraxella keratitis, although statistical significance was not achieved. However, there was an increasing trend in Grampositive organisms, particularly coagulase-negative staphylococci, and a decreasing trend in Gram-negative organisms, particularly pseudomonas, in our region (Table 1). Reassuringly we only identified two (0.5%) cases of methicillinresistant staphylococcus aureus (MRSA) over the past 10 years. This was in contrast to the considerably high prevalence of MRSA-related ocular infection reported in other countries [4]. In addition, acanthamoeba keratitis was more commonly associated with patients of younger age group as compared to those with Gram-positive, Gram-negative and fungal keratitis (Table 2). This was most likely related to the use of contact lens in younger patients.

Diabetic retinopathy and endothelin system: microangiopathy versus endothelial dysfunction.

Abstract: In the face of the global epidemic of diabetes, it is critical that we update our knowledge about the pathogenesis of diabetes and the related micro alterations on the vascular network in the body. This may ultimately lead to early diagnosis and novel treatment options for delaying the progression of diabetic complications. Research has recently revealed the pivotal role of endothelin in the pathogenesis of diabetic complications, particularly in the regulation of the capillary flow, which is affected in the course of retinopathy. Although there are several reviews on various approaches to the treatment of diabetes, including normalization of glucose and fat metabolism, no reviews in literature have focused on the endothelin system as a therapeutic target or early indicator of diabetic microangiopathy. In this review, we summarize some of the experimental and clinical evidence suggesting that current therapeutic approaches to diabetes may include the modulation of the blood concentration of compounds of the endothelin system. In addition, we will briefly discuss the beneficial effects produced by the inhibition of the production of high levels of endothelin in vasculopathy, with focus on diabetic retinopathy. The cutting-edge technology currently widely used in opththalmology, such as the OCT angiography, allows us to detect very early retinal morphological changes alongside alterations in choroidal and retinal vascular network. Combination of such changes with highly sensitive measurements of alterations in serum concentrations of endothelin may lead to more efficient early detection and treatment of diabetes and related macro/microvascular complications.

Three-year incidence of Nd:YAG capsulotomy and posterior capsule opacification and its relationship to monofocal acrylic IOL biomaterial: a UK Real World Evidence study.

Abstract: To evaluate 3-year incidence of Nd:YAG capsulotomy and PCO and compare the effect of different IOL materials. Data were retrospectively collected from seven UK ophthalmology clinics using Medisoft electronic medical records. Eyes from patients ≥65 years undergoing cataract surgery with implantation of acrylic monofocal IOLs during 2010–2013 and 3-year follow-up were analysed. Nd:YAG capsulotomy and PCO incidence proportions were reported for 3 IOL cohorts: AcrySof, other hydrophobic and hydrophilic acrylic IOLs. Unadjusted/adjusted odds ratios (OR) of Nd:YAG capsulotomy were calculated through logistic regression for non-AcrySof cohorts versus AcrySof. A sub-group analysis in single-piece IOLs (>90% of sample eyes) was also performed. The AcrySof cohort included 13,329 eyes, non-AcrySof hydrophobic 19,025 and non-AcrySof hydrophilic 19,808. The 3-year Nd:YAG capsulotomy incidence (95% CI) for AcrySof (2.4%, 2.2–2.7%) was approximately two times lower than non-AcrySof hydrophobic IOLs (4.4%, 4.1–4.7%) and approximately fourfold lower than non-AcrySof hydrophilic IOLs (10.9%, 10.5–11.3%). Trends were similar in PCO incidence (AcrySof: 4.7%; non-AcrySof hydrophobic: 6.3%; non-AcrySof hydrophilic: 14.8%). Also in the analysis restricted to single-piece IOLs, the pattern remained (2.4% vs 5.1% vs. 10.9%, respectively). Adjusted regression analysis showed a approximately two and fivefold increased odds of Nd:YAG for non-AcrySof hydrophobic and hydrophilic acrylic IOLs respectively vs. AcrySof IOLs. Nd:YAG capsulotomy ORs were similar and remained statistically significant in the single-piece IOL sub-group. Real-world evidence shows that within 3 years following implantation, AcrySof IOLs are significantly superior in reducing Nd:YAG capsulotomy and PCO incidence compared to other hydrophilic and hydrophobic acrylic IOLs.

Genetics and genetic testing for age-related macular degeneration.

Abstract: Considerable advances have been made in our understanding of age-related macular degeneration (AMD) genetics over the past decade. The genetic associations discovered to date are estimated to account for approximately half of AMD heritability, and functional studies of these variants have revealed new insights into disease pathogenesis, leading to the development of potential novel therapies. There is furthermore growing interest in genetic testing for predicting an individual's risk of AMD and offering personalised preventive or therapeutic treatments. We review the progress made so far in AMD genetics and discuss the possible applications for genetic testing.

Orbital decompression for thyroid eye disease: methods, outcomes, and complications.

Abstract: PurposeTo determine the safety and effectiveness of orbital decompression for thyroid eye disease (TED) in our unit. To put this in the context of previously published literature.Patients and methodsA retrospective case review of all patients undergoing orbital decompression for TED under the care of one orbital surgeon (SMS) between January 2009 and December 2015. A systematic literature review of orbital decompression for TED.ResultsWithin the reviewed period, 93 orbits of 55 patients underwent decompression surgery for TED. There were 61 lateral (single) wall decompressions, 17 medial one-and-a-half wall, 11 two-and-a-half wall, 2 balanced two wall, and 2 orbital fat only decompressions. For the lateral (single) wall decompressions, mean reduction in exophthalmometry (95% confidence interval (CI) was 4.2 mm (3.7-4.8), for the medial one-and-a-half walls it was 2.9 mm (2.1-3.7), and for the two-and-a-half walls it was 7.6 mm (5.8-9.4). The most common complications were temporary postoperative numbness (29% of lateral decompressions, 17% of other bony decompressions, OR 0.50, 95% CI 0.12-2.11) and new postoperative diplopia (9% of lateral decompressions, 39% of other bony decompressions, OR 6.8, 95% CI 1. 5-30.9). Systematic literature searching showed reduction in exophthalmometry for lateral wall surgery of 3.6-4.8 mm, with new diplopia 0-38% and postoperative numbness 12-50%. For other bony decompressions, reduction in exophthalmometry was 2.5-8.0 mm with new diplopia 0-45% and postoperative numbness up to 52%.ConclusionDiffering approaches to orbital decompression exist. If the correct type of surgery is chosen, then safe, adequate surgical outcomes can be achieved.

Role of pericytes in the retina.

Abstract: Diabetic retinopathy is a major severe ocular complication associated with the metabolic disorder of diabetes mellitus.1 The lack of a detailed knowledge about the cellular and molecular mechanisms involved in diabetic retinopathy restricts the design of effective treatments. Understanding the roles of retinal cells during this process is of utmost importance, since gaining control of specific cell populations may allow us to arrest or even induce reversion of diabetic retinopathy. Pericyte dropout or loss has been suggested to have great consequences on blood vessel remodeling, and possibly causes the first abnormalities of the diabetic eye which can be observed clinically in diabetic retinopathy.2 Nevertheless, a concreate evidence to support this concept is not available. Surprisingly, in a recent article in Nature Communications, Park and colleagues demonstrated that pericytes are not essential in the adult stable retinal blood vessels; and their selective depletion did not lead to a phenotype similar to diabetic retinopathy.3 The authors used a transgenic mouse model which can be used to specifically ablate PDGFRβexpressing pericytes (PDGFRβ-CreER/DTA mice). Several studies suggest that PDGFB released from vascular endothelial cells recruits PDGFRβ-expressing pericytes to facilitate vascular stabilization during blood vessel development.4 Nonetheless, whether this PDGFB/PDGFRβ signaling continues to be necessary for proper pericyte attachment to stable adult retinal vasculature was unknown. Park and colleagues used VE-Cadherin (Endothelial specific)-CreER/PDGFB floxed mice and intra-vitreal administration of PDGFRβ blocking antibody to show that PDGFB/ PDGFRβ signaling is not required for the maintenance of the interaction between pericytes and endothelial cells, and for the integrity of the blood-retinal-barrier in adults.3 In contrast, Park and colleagues demonstrated using state-of-the-art techniques, including deletion of several genes from endothelial cells, that PDGFB/PDGFRβ signaling is indispensable in the formation and maturation of bloodretinal-barrier at the postnatal stage through active recruitment of pericytes onto the growing retinal vessels.3 Additionally, the authors revealed that pericytes are important in the adult retina as regulators, as they control the expression of several genes (FOXO1, Ang2, and VEGFR2) to protect retinal vessels against injuries and stresses.3 Here, we discuss the findings from this work, and evaluate recent advances in our understanding of pericytes roles in the retina.

The Royal College of Ophthalmologists recommendations on screening for hydroxychloroquine and chloroquine users in the United Kingdom: executive summary

Abstract: The Royal College of Ophthalmologists recently published recommendations for retinal screening in users of hydroxychloroquine and chloroquine in the United Kingdom [1]. This article forms a summary of the key components of the guideline. These recommendations involve a range of stakeholders including patients, Ophthalmologists and the hospital eye service, Rheumatologists, Dermatologists, General Practitioners, community optometry services, healthcare commissioners, and patient groups/ voluntary organisations who have had input into the development of the guideline. The full guideline can be found online at: https://www. rcophth.ac.uk/standards-publications-research/clinicalguidelines/. The criteria used for grading evidence is specified in Table 1, and the recommendations and grade of evidence supporting them are detailed in Table 2a, 2b, 2c, 2d, 2e, 2f, 2g. (Fig. 1).Table 2c is a standardised screening protocol that applies to all patients. A comprehensive non-systematic review of hydroxychloroquine retinopathy which summarises the evidence at the time of guideline development is available [2].

An international comparison of retinopathy of prematurity grading performance within the Benefits of Oxygen Saturation Targeting II trials.

Abstract: PurposeTo investigate whether the observed international differences in retinopathy of prematurity (ROP) treatment rates within the Benefits of Oxygen Saturation Targeting (BOOST) II trials might have been caused by international variation in ROP disease grading.MethodsGroups of BOOST II trial ophthalmologists in UK, Australia, and New Zealand (ANZ), and an international reference group (INT) used a web based system to grade a selection of RetCam images of ROP acquired during the BOOST II UK trial. Rates of decisions to treat, plus disease grading, ROP stage grading, ROP zone grading, inter-observer variation within groups and intra-observer variation within groups were measured.ResultsForty-two eye examinations were graded. UK ophthalmologists diagnosed treat-requiring ROP more frequently than ANZ ophthalmologists, 13.9 (3.49) compared to 9.4 (4.46) eye examinations, P=0.038. UK ophthalmologists diagnosed plus disease more frequently than ANZ ophthalmologists, 14.1 (6.23) compared to 8.5 (3.24) eye examinations, P=0.021. ANZ ophthalmologists diagnosed stage 2 ROP more frequently than UK ophthalmologists, 20.2 (5.8) compared to 12.7 (7.1) eye examinations, P=0.026. There were no other significant differences in the grading of ROP stage or zone. Inter-observer variation was higher within the UK group than within the ANZ group. Intra-observer variation was low in both groups.ConclusionsWe have found evidence of international variation in the diagnosis of treatment-requiring ROP. Improved standardisation of the diagnosis of treatment-requiring ROP is required. Measures might include improved training in the grading of ROP, using an international approach, and further development of ROP image analysis software.

Mesopic and dark-adapted two-color fundus-controlled perimetry in patients with cuticular, reticular, and soft drusen.

Abstract: To examine the feasibility and utility of dark-adapted two-color fundus-controlled perimetry (FCP) in patients with cuticular, reticular, and soft drusen, and to compare FCP data to microstructural spectral-domain optical coherence tomography (SD-OCT) data. Forty-four eyes (24 eyes of 24 patients with drusen, age 69.4 ± 12.6 years; 20 normal eyes of 16 subjects, 61.7 ± 12.4 years) underwent duplicate mesopic, dark-adapted cyan and dark-adapted red FCP within 14° of the central retina (total of 12 936 threshold tests) using the Scotopic Macular Integrity Assessment (S-MAIA, CenterVue, Padova, Italy) device. FCP data were registered to SD-OCT data to obtain outer nuclear layer, inner and outer photoreceptor segment, and retinal pigment epithelium drusen complex (RPEDC) thickness data spatially corresponding to the stimulus location and area (0.43°). Structure-function correlations were assessed using mixed-effects models. Mean deviation values for eyes with cuticular, soft, and reticular drusen were similar for mesopic (−2.1, −3.4, and −3.6 dB) and dark-adapted red (−1.4, −2.6, and −3.3 dB) FCP. For the dark-adapted cyan FCP (0.1, −1.9, and −5.0 dB) and for the cyan–red sensitivity difference (+1.0, +0.5, and −2.4 dB), the mean deviation values differed significantly in dependence of the predominant drusen type (one-way ANOVA; p < 0.05). RPEDC thickness was associated with reduction of mesopic sensitivity (−0.34 dB/10 µm RPEDC thickening; p < 0.001), dark-adapted cyan sensitivity (−0.11 dB/10 µm RPEDC thickening; p = 0.003), and dark-adapted red sensitivity (−0.26 dB/10 µm RPEDC thickening; p < 0.001). In contrast to mesopic FCP, dark-adapted two-color FCP allowed for meaningful differential testing of rod and cone function in patients with drusen indicating predominant cone dysfunction in eyes with cuticular drusen and predominant rod dysfunction in eyes with reticular drusen. RPEDC thickness was the strongest predictor of the evaluated SD-OCT biomarkers for point-wise sensitivity.

Visual outcomes and anatomic changes after sub-threshold micropulse yellow laser (577-nm) treatment for chronic central serous chorioretinopathy: long-term follow-up.

Abstract: To analyze the long-term efficacy of 577 nm sub-threshold micropulse yellow laser (SMYL) in the treatment of chronic central serous chorioretinopathy (CCSC) and to evaluate the anatomic outcome, visual results and safety profile of the treatment. This prospective study assessed 39 eyes of 39 patients with non-resolving CCSC lasting more than three months. All eyes were treated by using 577 nm SMYL system with 5% duty cycle (DC) and each patients was monitored monthly. The main outcome measures were best-corrected visual acuity (BCVA), contrast sensitivity (CS) and subretinal fluid (SRF) height, central macular thickness (CMT), central macular volume (CMV), total macular volume (TMV), and subfoveal choroidal thickness (SFCT) measured by spectral domain optical coherence tomography (SD-OCT). The median follow-up time period was 17.82±0.42 (13−23 months) months. The BCVA was improved significantly at final follow-up in comparison of baseline visit (P<0.01) in 35 eyes (89.7%) and in 4 eyes (10.3%) was stable. The median CMT, CMV, TMV before treatment was 369 μm, 0.30 mm3, and 9.86 mm3, in comparison to 250 μm, 0.19 mm3, and 8.76 mm3 at final follow-up, respectively (P<0.01 for all these parameters). Initial median SFCT was recorded as 364 μm and 342 μm at the final follow-up (P<0.001). Results suggest that SMYL treatment is an effective method as response was rapid and procedure is safe to manage the non-resolving CCSC eyes.

Generation of customized orbital implant templates using 3-dimensional printing for orbital wall reconstruction

Abstract: To describe and evaluate a novel surgical approach to orbital wall reconstruction that uses three-dimensionally (3D) printed templates to mold a customized orbital implant. A review was conducted of 11 consecutive patients who underwent orbital wall reconstruction using 3D-printed customized orbital implant templates. In these procedures, the orbital implant was 3D pressed during surgery and inserted into the fracture site. The outcomes of this approach were analyzed quantitatively by measuring the orbital tissue volumes within the bony orbit using computed tomography. All 11 orbital wall reconstructions (6 orbital floor and 5 medial wall fractures) were successful with no post operative ophthalmic complications. Statistically significant differences were found between the preoperative and post operative orbital tissue volumes for the affected orbit (24.00 ± 1.74 vs 22.31 ± 1.90 cm3; P = 0.003). There was no statistically significant difference found between the tissue volume of the contralateral unaffected orbit and the affected orbit after reconstruction (22.01 ± 1.60 cm3 vs 22.31 ± 1.90 cm3; P = 0.182). 3D-printed customized orbital implant templates can be used to press and trim conventional implantable materials with patient-specific contours and sizes for optimal orbital wall reconstruction. It is difficult to design an orbital implant that exactly matches the shape and surface of a blowout fracture site due to the unique 3D structure of the orbit. The traditional surgical method is to visually inspect the fracture site and use eye measurements to cut a two-dimensional orbital implant that corresponds to the anatomical structure of the fracture site. However, implants that do not fit the anatomical structure of a fracture site well can cause complications such as enophthalmos, diplopia and displacement of the implant.

The thick and thin of the central corneal thickness in glaucoma.

Abstract: Central corneal thickness (CCT) is an important parameter in the assessment of any potential glaucoma patient. While it affects prognosis in ocular hypertension, its value in patients diagnosed with glaucoma is less certain. There are several biological factors and genetic components that may influence glaucoma progression, which have been associated with thinner CCT. The CCT itself can be affected by several factors including ethnicity, age, sex, glaucoma medications, genetics, and the subtype of glaucoma. Besides, there is variability in the measurement of CCT between difference types of devices. These factors need to be considered in the evaluation of glaucoma patients' CCT and its effect on interpretation of intraocular pressure levels and risk stratification.

Anterior segment ischemia: etiology, assessment, and management.

Abstract: Anterior segment ischemia (ASI) is a potentially serious but rare complication of strabismus surgery. Among several risk factors, ASI occurs after strabismus surgery because of the nature of the anterior segment circulation. Disinsertion of rectus muscles leads to a decrease in the blood supply to the various anterior segment structures. We report a series of retrospective and prospective studies performed by our group focused on determining the risk of anterior segment ischemia following strabismus surgery, diagnosis, and modifications to surgical techniques to minimize the impact on anterior segment circulation. We found a significant decrease in postoperative anterior segment blood flow when operating vertical rectus muscles. Plication procedures preserve anterior segment circulation, and modifications to the technique allow the performance of adjustable sutures. Small adjustable selective procedures that spare the ciliary vessels have been demonstrated to be effective in patients with vertical and torsional diplopia. Ciliary sparing augmented adjustable transposition surgery decreases the risk of anterior segment ischemia while allowing management of potential post-operative alignment complications. Finally, ocular coherence tomography angiography is a valuable quantitative and qualitative technique to evaluate anterior segment ischemia. Strabismus surgeons should be aware of the risks of anterior segment ischemia when operating vertical rectus muscles. Modifications to standard surgical techniques allow surgeons to perform complex strabismus surgery in patients at risk for anterior segment ischemia.

Ocular syphilis: the re-establishment of an old disease

Abstract: PurposeTo present the patient profiles, clinical presentations and visual outcomes in those diagnosed with ocular syphilis, attending a subspecialist uveitis service in northern England over a 15-year period.Patients and methodsRetrospective observational case series of patients presenting between January 2002 and December 2016.ResultsA total of 50 eyes of 34 patients had intraocular inflammation due to syphilis. Of these, 94% were male, and 75% were men who had sex with men. Ten (29%), all male, were HIV-positive. Presentations included isolated anterior non-granulomatous uveitis, intermediate uveitis, panuveitis, retinitis, placoid chorioretinitis and papillitis. Concurrent skin rash and/or headache were seen in 41%. Compliance with antibiotic treatment was complete, but there was a high rate of default from ophthalmological follow-up (38%). Visual improvement was seen in 92% of eyes, and at final assessment 71% had acuity of 6/9 or better.ConclusionsOcular syphilis is continuing to increase in incidence, in tandem with the continuing epidemic of early syphilis in the UK (the risk of ocular involvement being about 1%). Almost all are male, and most are men who have sex with men. Clinical presentation is variable; a high index of suspicion and a low threshold for serological testing is important; early treatment can reverse retinal changes and restore visual acuity.